MRC Centre for Neuromuscular Disease Neuropathies associated with myeloma and other plasma cell disorders UK Myeloma Forum Meeting London November 2011 Dr Michael Lunn Consultant Neurologist and Clinical Lead in Neuroimmunology National Hospital for Neurology and Neurosurgery Queen Square London WC1N 3BG [email protected]
MRC Centre for Neuromuscular Disease. Neuropathies associated with myeloma and other plasma cell disorders UK Myeloma Forum Meeting London November 2011. Dr Michael Lunn Consultant Neurologist and Clinical Lead in Neuroimmunology - PowerPoint PPT Presentation
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
MRC Centre for Neuromuscular Disease
Neuropathies associated with myeloma and other plasma cell
disorders
UK Myeloma Forum MeetingLondon November 2011
Dr Michael LunnConsultant Neurologist and Clinical Lead in Neuroimmunology
National Hospital for Neurology and NeurosurgeryQueen Square
Common Terminology Criteria for Adverse Events v3.0 (CTCAE) – 2006….is a descriptive terminology which can be utilized for adverse event (AE) reporting.
• Grades 1-5 (minimal involvement – death)• Not really useful for neuropathy, or indeed very
much neurological• There is a lot more to neuropathy than CTCAE
Neuropathies associated with plasma cell disorders
• Anatomy revision
• Neuropathies associated with plasma cell disorders
• Typical and atypical presentations
• Toxicities of treatment
VESALIUS, Andreas (1514-1564)De humani corporis fabrica, Basel: Oporinus, 1543.lib. IV, pp.353-4Wellcome Library, London
skin
Background to ‘inflammatory’ neuropathy
• Paraprotein associated neuropathies part of group of inflammatory neuropathies
• Diverse group of disorders with presumed ‘immune mediated’ pathogenesis
• Inflammatory endoneurial infiltration and destruction of myelin and/or axons
– Elderly male, mild ataxia, tremor and unsteadiness – no falls
– No weakness, distal PP loss and VS to costal margin– IgMκ paraprotein, and demyelinating neuropathy– Anti-MAG antibody positive >70000 Bühlmann Units
Watch and wait….
You may do more good with a stick and some trainers…
• Are you treating the right thing?– 62 female– Long history severe OA and immobility. Smoker– Numb, painful red feet and ‘venous ulcers’ – Pronounced distal motor loss. PP=VS/JPS loss– Demyelinating neurophysiology– 4 x IgMκ paraproteins and anti-MAG antibodies
• Vasculitis and acquired erythermalgia with vasculitic neuropathy
• CD138 <5% plasma cells but IgM k restricted – ‘appearances are suggestive of myeloma than lymphoplasmacytic lymphoma…IgM very rare’
• Scheinker 1938– PN, solitary myeloma and sclerotic pigmented skin
• Crow-Fukase 1956– Increasingly complex relationships of MM and PN
• Bardwick 1980– Coined acronym
• 0.3/100000 Japan (Arimura 2007)
POEMS syndrome diagnostic criteria
Polyneuropathy and monoclonal plasma cell disorder present in all patients; to make diagnosis at least one other major criterion and 1 minor criterion is required.
• Major Criteria• Polyneuropathy• Monoclonal plasma cell disorder
• Possible associations• Arthralgia• Cardiomyopathy• Fever
*DM and thyroid disease are very common and occurrence of one only not sufficient**Anaemia and thrombocytopaenia distinctly unusual unless Castleman disease present
Dispenzieri 2007
POEMSfrequency and variability of clinical features
Kuwabara S, Dispenzieri A et al Cochrane 2008 Issue 4
POEMS treatment 2
• Autologous PBSCT• 49 patients – all but one survived 2 years• ?4% mortality in POEMS (vs 2% for other indications)
• Treatment directed at relevant pathogenic aspects of disease with good effect
Kuwabara S, Dispenzieri A et al Cochrane 2008 Issue 4
POEMS or not POEMS?
Mononeuropathies and plasma cell disorders
• Multiple myeloma• Neurolymphomatosis• Cryoglobulinaemia• Amyloidosis• Associated by chance
Acquired amyloid neuropathy
• AL amyloid• MM, MGUS, malignant lymphoma,
Waldenstrom’s macroglobulinaemia• λ >> κ light chains• Deposition of light chain in nerve
Amyloid neuropathy• Length dependent axonal
• sensory loss with prominent small fibre involvement• Pain is often burning, especially nocturnally, or as lancinating stabs• Pain and temperature are selectively involved