XClose

UCL Queen Square Institute of Neurology

Menu

Neuroimmunology Unit

  • Laboratory Lead: Dr Melanie Hart
  • Clinical Lead and Consultant Neurologist: Professor Michael Lunn
  • Honorary Senior Lecturer and Consultant Neurologist: Dr Michael Zandi

The Neuroimmunology and CSF Laboratory (NICL) at the UCL Queen Square Institute of Neurology is one of very few specialist NHS Neuroimmunology Laboratories in the UK and provides a hub for CSF and Neuroimmunology testing for UCLH, the Greater London network and beyond. NICL is situated adjacent to and serves the National Hospital for Neurology and Neurosurgery (NHNN) for clinical testing services. Both are part of University College Hospitals NHS Trust. The NHS Neuroimmunology service has developed from its beginnings in the 1980s in collaboration with Emeritus Professor Edward Thompson. A strong focus on in-house research has led to the development of many novel diagnostic assays for neurology such as oligoclonal bands (OCBS) developed to aid diagnosis of inflammatory central nervous system disorders such as Multiple Sclerosis; OCBS are still in routine use today throughout the world.

The laboratory now provides a comprehensive neuroimmunology testing service to physicians in the UK and beyond. Staff hold honorary contracts with University College London (UCL) through which they are facilitated to pursue relevant research and some sit on external quality assurance steering committees for CSF analysis, providing expert guidance advice and standardisation to the UK and further afield.

The team at NICL is at the forefront of biomarker research into many neurological and neuroinflammatory diseases including Multiple Sclerosis and Autoimmune Encephalitis, Dementias, and inflammatory peripheral nerve diseases including POEMS syndrome. In 2020, NICL rapidly established a clinical Cytokine Storm assay to identify, and prognosticate for, the most severely affected COVID-19 patients in UCLH, publishing clinically useful data in an international journal. NICL is associated with the Wolfson Biomarker Laboratory (WBL) and the biomarker laboratory of the Leonard Wolfson Experimental Neurology Centre (LWENC) led by Professor Henrik Zetterberg alongside whom CSF and serum neurofilament light chain measurement and other dementia biomarkers are being investigated and developed. NICL has close links with both the Dementia Research Centre collaborating on research into the clinical utility of dementia biomarkers, and the NHNN neurosurgeons who are exploring biomarkers in the decision-making processes for the treatment of hydrocephalus. The team collaborates closely with many of the neurologists based at NHNN to improve clinical care. NICL also provide an analytical service for congenital disorders of glycosylation (CDG). Within these collaborations, members of the NICL staff have co-authored papers with GOSH and ICH researchers locally and other international groups in wider projects.

NICL supports a number of PhD and research fellows both from within their own staff and also clinical fellows pursuing independent research. These fellows support the research efforts in all areas of neurological disease as well as the clinical validation and verification of assays for clinical use.

The clinical lead, Professor Michael Lunn, is leading several research studies into biomarkers in peripheral nerve diseases such as novel autoantibodies in inflammatory neuropathies and VEGF and other biomarkers in POEMS, Guillain-Barré syndrome and amyloidosis. These peripheral nerve diseases can result in profound, significant and frequently permanent disabilities when not treated promptly or appropriately. Biomarkers are needed to know when and how to treat, to predict relapse or outcome and monitor the effects of therapy. For example, paraproteinaemic neuropathies frequently require no treatment but in others the treatment may involve potentially toxic chemotherapy; POEMS syndrome is treated with autologous bone marrow transplantation and early appropriate identification of patients using serum light chains and VEGF provides early and accurate diagnostic data. Neurofilament Light (NFL) and some other novel damage biomarkers can help predict relapse and the need for treatment.

The laboratory has a developing research interest in mechanisms of autoimmune (antibody mediated) encephalitis (for example NMDA-R mediated encephalitis), headed up by Dr Mike Zandi. Within the space of paraneoplastic disorders, retinal antibodies are also a key focus of the laboratory and we are developing our panel further in association with UCLH and Moorfields hospital.

Translational research into serum and CSF assays used by the NHS, both for UCLH and the UK is a key aim of the laboratory and we aim to extend our repertoire of autoantibody and biomarker tests for neurological disorders. We are fortunate to have received a charitable grant from the National Brain Appeal and the UCLH Charities to purchase the first Single Molecule Analyser (SiMOA) in the UK for clinical use.

Neuroimmunology and CSF Laboratory Publications 2012 to 2020

2020

  • Keddie S, Ziff O, Chou MKL, Taylor RL, Heslegrave A, Garr E, Lakdawala N, Church A, Ludwig D, Manson J, Scully M, Nastouli E, Chapman MD, Hart M, Lunn MP. Laboratory biomarkers associated with COVID-19 severity and management. Clin Immunol. 2020 Dec; 221:108614. doi: 10.1016/j.clim.2020.108614. Epub 2020 Oct 22.
  • Marsh ES, Keddie S, Terris-Prestholt F, D'Sa S, Lunn MP. Early VEGF testing in inflammatory neuropathy avoids POEMS syndrome misdiagnosis and associated costs. J Neurol Neurosurg Psychiatry. 2020 Oct 26: jnnp-2020-324012. doi: 10.1136/jnnp-2020-324012. Online ahead of print.
  • Keshavan A, Wellington H, Chen Z, Khatun A, Chapman M, Hart M, Cash DM, Coath W, Parker TD, Buchanan SM, Keuss SE, Harris MJ, Murray-Smith H, Heslegrave A, Fox NC, Zetterberg H, Schott JM. Concordance of CSF measures of Alzheimer's pathology with amyloid PET status in a preclinical cohort: A comparison of Lumipulse and established immunoassays. Alzheimers Dement (Amst). 2020 Sep 13;12(1): e12097. doi: 10.1002/dad2.12097. eCollection 2020.
  • Varley JA, Andersson M, Grant E, Berretta A, Zandi MS, Bondet V, Duffy D, Hunt D, Piehl F, Waters P, Irani SR. Absence of Neuronal Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus. Ann Neurol. 2020 Dec;88(6):1244-1250. doi: 10.1002/ana.25908. Epub 2020 Oct 6.
  • Zambreanu L, Lightbody S, Bhandari M, Hoskote C, Kandil H, Houlihan CF, Lunn MP. A case of limbic encephalitis associated with asymptomatic COVID-19 infection. J Neurol Neurosurg Psychiatry. 2020 Nov;91(11):1229-1230. doi: 10.1136/jnnp-2020-323839. Epub 2020 Jul 13.
  • Paterson RW, Brown RL, Benjamin L, Nortley R, Wiethoff S, Bharucha T, Jayaseelan DL, Kumar G, Raftopoulos RE, Zambreanu L, Vivekanandam V, Khoo A, Geraldes R, Chinthapalli K, Boyd E, Tuzlali H, Price G, Christofi G, Morrow J, McNamara P, McLoughlin B, Lim ST, Mehta PR, Levee V, Keddie S, Yong W, Trip SA, Foulkes AJM, Hotton G, Miller TD, Everitt AD, Carswell C, Davies NWS, Yoong M, Attwell D, Sreedharan J, Silber E, Schott JM, Chandratheva A, Perry RJ, Simister R, Checkley A, Longley N, Farmer SF, Carletti F, Houlihan C, Thom M, Lunn MP, Spillane J, Howard R, Vincent A, Werring DJ, Hoskote C, Jäger HR, Manji H, Zandi MS. The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain. 2020 Oct 1;143(10):3104-3120. doi: 10.1093/brain/awaa240.
  • Keddie S, Foldes D, Caimari F, Baldeweg SE, Bomsztyk J, Ziff OJ, Fehmi J, Cerner A, Jaunmuktane Z, Brandner S, Yong K, Manji H, Carr A, Rinaldi S, Reilly MM, D'Sa S, Lunn MP. Clinical characteristics, risk factors, and outcomes of POEMS syndrome: A longitudinal cohort study. Neurology. 2020 Jul 21;95(3):e268-e279. doi: 10.1212/WNL.0000000000009940. Epub 2020 Jun 30.
  • Ellul M, Varatharaj A, Nicholson TR, Pollak TA, Thomas N, Easton A, Zandi MS, Manji H, Solomon T, Carson A, Turner MR, Kneen R, Galea I, Pett S, Thomas RH, Michael BD; CoroNerve Steering Committee. Defining causality in COVID-19 and neurological disorders. J Neurol Neurosurg Psychiatry. 2020 Aug;91(8):811-812. doi: 10.1136/jnnp-2020-323667. Epub 2020 Jun 5.
  • Gibson LL, McKeever A, Cullen AE, Nicholson TR, Aarsland D, Zandi MS, Pollak TA. Neuronal surface autoantibodies in dementia: a systematic review and meta-analysis. J Neurol. 2020 Apr 18. doi: 10.1007/s00415-020-09825-0. Online ahead of print.
  • Altmann P, De Simoni D, Kaider A, Ludwig B, Rath J, Leutmezer F, Zimprich F, Hoeftberger R, Lunn MP, Heslegrave A, Berger T, Zetterberg H, Rommer PS. Increased serum neurofilament light chain concentration indicates poor outcome in Guillain-Barré syndrome. J Neuroinflammation. 2020 Mar 17;17(1):86. doi: 10.1186/s12974-020-01737-0.
  • Banerjee G, Ambler G, Keshavan A, Paterson RW, Foiani MS, Toombs J, Heslegrave A, Dickson JC, Fraioli F, Groves AM, Lunn MP, Fox NC, Zetterberg H, Schott JM, Werring DJ. Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy. J Alzheimers Dis. 2020;74(4):1189-1201. doi: 10.3233/JAD-191254.

2019

  • Kapoor M, Foiani M, Heslegrave A, Zetterberg H, Lunn MP, Malaspina A, Gillmore JD, Rossor AM, Reilly MM. Plasma neurofilament light chain concentration is increased and correlates with the severity of neuropathy in hereditary transthyretin amyloidosis. J Peripher Nerv Syst. 2019 Dec;24(4):314-319. doi: 10.1111/jns.12350. Epub 2019 Oct 14.
  • Cunningham EL, McGuinness B, McAuley DF, Toombs J, Mawhinney T, O'Brien S, Beverland D, Schott JM, Lunn MP, Zetterberg H, Passmore AP. CSF Beta-amyloid 1-42 Concentration Predicts Delirium Following Elective Arthroplasty Surgery in an Observational Cohort Study. Ann Surg. 2019 Jun;269(6):1200-1205. doi: 10.1097/SLA.0000000000002684.
  • Ehler J, Petzold A, Wittstock M, Kolbaske S, Gloger M, Henschel J, Heslegrave A, Zetterberg H, Lunn MP, Rommer PS, Grossmann A, Sharshar T, Richter G, Nöldge-Schomburg G, Sauer M. The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy - A prospective, pilot observational study. PLoS One. 2019 Jan 24;14(1):e0211184. doi: 10.1371/journal.pone.0211184. eCollection 2019.
  • Craven CL, Chapman MD, D'Antona L, Thompson SD, Lakdawala N, Zetterberg H, Watkins LD, Toma AK. Lumbar drains can affect CSF biomarker levels. J Clin Pathol. 2019 Jan;72(1):91-92. doi: 10.1136/jclinpath-2018-205296. Epub 2018 Jul 11.

2018

  • Lennox BR, Tomei G, Vincent SA, Yeeles K, Pollard R, Palmer-Cooper E, Jones P, Zandi MS, Coles A. Study of immunotherapy in antibody positive psychosis: feasibility and acceptability (SINAPPS1). J Neurol Neurosurg Psychiatry. 2019 Mar;90(3):365-367. doi: 10.1136/jnnp-2018-318124. Epub 2018 Jun 11.
  • Toombs J, Foiani MS, Wellington H, Paterson RW, Arber C, Heslegrave A, Lunn MP, Schott JM, Wray S, Zetterberg H. Amyloid β peptides are differentially vulnerable to preanalytical surface exposure, an effect incompletely mitigated by the use of ratios. Alzheimers Dement (Amst). 2018 Mar 22;10:311-321. doi: 10.1016/j.dadm.2018.02.005. eCollection 2018.
  • Paterson RW, Slattery CF, Poole T, Nicholas JM, Magdalinou NK, Toombs J, Chapman MD, Lunn MP, Heslegrave AJ, Foiani MS, Weston PSJ, Keshavan A, Rohrer JD, Rossor MN, Warren JD, Mummery CJ, Blennow K, Fox NC, Zetterberg H, Schott JM. Cerebrospinal fluid in the differential diagnosis of Alzheimer's disease: clinical utility of an extended panel of biomarkers in a specialist cognitive clinic. Alzheimers Res Ther. 2018 Mar 20;10(1):32. doi: 10.1186/s13195-018-0361-3.
  • Midgley L, Kelleher E, Zandi MS. Autoimmune encephalitis. Br J Hosp Med (Lond). 2018 Sep 2;79(9):C134-C137. doi: 10.12968/hmed.2018.79.9.C134.
  • Pihan M, Keddie S, D'Sa S, Church AJ, Yong KL, Reilly MM, Lunn MP. Raised VEGF: High sensitivity and specificity in the diagnosis of POEMS syndrome. Neurol Neuroimmunol Neuroinflamm. 2018 Aug 15;5(5): e486. doi: 10.1212/NXI.0000000000000486. eCollection 2018 Sep.
  • Keddie S, Crisp SJ, Blackaby J, Cox A, Coles A, Hart M, Church AJ, Vincent A, Zandi M, Lunn MP. Plasma cell depletion with bortezomib in the treatment of refractory N-methyl-d-aspartate (NMDA) receptor antibody encephalitis. Rational developments in neuroimmunological treatment. Eur J Neurol. 2018 Nov;25(11):1384-1388. doi: 10.1111/ene.13759. Epub 2018 Aug 31.

2017

  • Craven C, Baudracco I, Zetterberg H, Lunn MPT, Chapman MD, Lakdawala N, Watkins LD, Toma AK. The predictive value of T-tau and AB1-42 levels in idiopathic normal pressure hydrocephalus. Acta Neurochir. 2017 9 September published online.
  • Kuhle J Nourbakhsh B, Grant D, Morant S, Barro C, Yaldizli Ö, Pelletier D, Giovannoni G, Waubant E, Gnanapavan S. Serum neurofilament is associated with progression of brain atrophy and disability in early MS. Neurology. 2017 Feb 28;88(9):826-831.
  • Craven CL, Baudracco I, Zetterberg H, Lunn MPT, Chapman MD, Lakdawala N, Watkins LD, Toma AK. The predictive value of T-tau and AB1-42 levels in idiopathic normal pressure hydrocephalus. Acta Neurochir (Wien). 2017 Dec;159(12):2293-2300. doi: 10.1007/s00701-017-3314-x. Epub 2017 Sep 9.

2016

  • Schirmer L, Worthington V, Solloch U, Loleit V, Grummel V, Lakdawala N, Grant D, Wassmuth R, Schmidt AH, Gebhardt F, Andlauer TF, Sauter J, Berthele A, Lunn MP, Hemmer B. Higher frequencies of HLA DQB1*05:01 and anti-glycosphingolipid antibodies in a cluster of severe Guillain-Barré syndrome J Neurol. 2016 Oct;263(10):2105-13.
  • Heywood WE, Bliss E, Mills P, Yuzugulen J, Carreno G, Clayton PT, Muntoni F, Worthington VC, Torelli S, Sebire NJ, Mills K, Grunewald S. Global serum glycoform profiling for the investigation of dystroglycanopathies & Congenital Disorders of Glycosylation. Mol Genet Metab Rep. 2016 17;7:55-62.
  • Zandi MS Autoimmune Encephalitis.Focus (Am Psychiatr Publ). 2016 Oct;14(4):432-436. doi: 10.1176/appi.focus.20160019. Epub 2016 Oct 7.
  • Zandi MS, Lennox B, Vincent A. N-Methyl-D-Aspartate Receptor Autoantibodies in Psychiatric Illness. Biol Psychiatry. 2016 May 1;79(9):e61. doi: 10.1016/j.biopsych.2015.03.034. Epub 2015 Jun 9.

2015

  • Paterson RW, Toombs J, Chapman MD, Nicholas JM, Heslegrave AJ, Slattery CF, Foulkes AJM, Clark CM, Lane CAS, Weston PSJ, Lunn MP, Fox NC, Zetterberg H, Schott JM. Do cerebrospinal fluid transfer methods affect measured amyloid b42, total tau and phosphorylated tau in clinical practice? Alzheimer’s and Dementia: Diagnosis, Assessment & Disease Monitoring 2015;1:380-384.
  • Kawagashira Y, Koike H, Ohyama K, Hashimoto R, Iijima M, Adachi H, Katsuno M, Chapman M, Lunn M, Sobue G. Axonal loss influences the response to rituximab treatment in neuropathy associated with IgM monoclonal gammopathy with anti-myelin-associated glycoprotein antibody. J Neurol Sci. 2015 Jan 15;348(1-2):67-73. doi: 10.1016/j.jns.2014.11.006. Epub 2014 Nov 13.

2014

  • Gnanapavan S, Yousaf N, Heywood W, Grant D, Mills K, Chernajovsky Y, Keir G, Giovannoni G. Growth associated protein (GAP-43): cloning and the development of a sensitive ELISA for neurological disorders. J Neuroimmunol. 2014 Nov 15;276(1-2):18-23..
  • Kawagashira Y, Koike H, Ohyama K, Hashimoto R, Iijima M, Adachi H, Katsuno M, Chapman M, Lunn M, Sobue G. Axonal loss influences the response to rituximab treatment in neuropathy associated with IgM monoclonal gammopathy with anti-myelin associated glycoprotein antibody. J Neurol Sci 2014;348;67-73.
  • Birch K, Burrows G, Cruickshank A, Egner W, Holbrook I, Lewis E, McNeilly J, Patel D, Worthington V. Cerebrospinal fluid total protein cannot reliably distinguish true subarachnoid haemorrhage from other causes of raised cerebrospinal fluid net bilirubin and net oxyhaemoglobin absorbances.Ann Clin Biochem. 2014 Nov;51(Pt 6):657-61.

2013

  • Gnanapavan S, Grant D, Morant S, Furby J, Hayton T, Teunissen CE, Leoni V, Marta M, Brenner R, Palace J, Miller DH, Kapoor R, Giovannoni G. Biomarker report from the phase II lamotrigine trial in secondary progressive MS - neurofilament as a surrogate of disease progression. PLoS One. 2013 Aug 1;8(8)
  • Gnanapavan S, Ho P, Heywood W, Jackson S, Grant D, Rantell K, Keir G, Mills K, Steinman L, Giovannoni G. Progression in multiple sclerosis is associated with low endogenous NCAM. J Neurochem. 2013 Jun;125(5):766-73
  • Toombs J, Paterson RW, Lunn MP, Nicholas JM, Fox NC, Chapman MD, Schott JM, Zetterberg H. Identification of an important potential confound in CSF AD studies: aliquot volume. Clin Chem Lab Med 2013;51(12);2311-17.
  • Heywood WE, Mills P, Grunewald S, Worthington V, Jaeken J, Carreno G, Lemonde H, Clayton PT, Mills K. A new method for the rapid diagnosis of protein N-linked congenital disorders of glycosylation. J Proteome Res. 2013 Jul 5;12(7):3471-9.

2012

  • Gnanapavan S, Grant D, Pryce G, Jackson S, Baker D, Giovannoni G. Neurofilament a biomarker of neurodegeneration in autoimmune encephalomyelitis. Autoimmunity. 2012 Jun;45(4):298-303.
  • Dale RC, Merheb V, Pillai S, Wang D, Cantrill L, Murphy TK, Ben-Pazi H, Varadkar S, Aumann TD, Horne MK, Church AJ, Fath T, Brilot F. Antibodies to surface dopamine-2 receptor in autoimmune movement and psychiatric disorders. Brain. 2012 Nov;135(Pt 11):3453-68. doi: 10.1093/brain/aws256. Epub 2012 Oct 11.
  • Nicholson TR, Ferdinando S, Krishnaiah RB, Anhoury S, Lennox BR, Mataix-Cols D, Cleare A, Veale DM, Drummond LM, Fineberg NA, Church AJ, Giovannoni G, Heyman I. Prevalence of anti-basal ganglia antibodies in adult obsessive-compulsive disorder: cross-sectional study. Br J Psychiatry. 2012 May;200(5):381-6. doi: 10.1192/bjp.bp.111.092007. Epub 2012 Jan 26.