MGUS PN Flashcards
What percentage of people over 70 have MGUS?
5.3%
What percentage of patients with MG-IgM develop peripheral neuropathy?
50% of patients with MG-IgM develop peripheral neuropathy.
What is the role of protein electrophoresis in evaluating M-protein?
It quantitatively evaluates the M-protein when detectable.
What information does immunofixation provide about M-protein?
Subtype of M-protein (also very sensitive for M protein)
Which size fibers are mainly affected in DADS?
Large sensory fibers.
What symptoms are usually presented in DADS?
Distal hypoesthesia, sensory ataxia, and minimal or no weakness.
What percentage of DADS patients have no detectable IgM MG?
One-third of DADS patients have no detectable IgM MG.
What is the CIDP variant called when DADS patients lack IgM MG?
It is referred to as distal CIDP.
What percentage of DADS cases with IgM MG present anti-MAG antibodies?
67% of DADS cases with IgM MG present anti-MAG antibodies.
What MAG antibody BTU titer is less likely to be related to neuropathy?
Titers smaller than 8000 BTU are less likely related to neuropathy.
Nerve conduction studies show what key findings in anti-MAG-associated neuropathies?
Disproportionally prolonged distal motor latency and reduced conduction velocity.
What terminal latency index (TLI) value increases likelihood of anti-MAG-associated neuropathies?
TLI < 0.26 increases likelihood.
Are conduction block and temporal dispersion common in anti-MAG-associated neuropathies?
No, they are rarely seen.
What is the most common syndrome associated with anti-MAG antibodies?
DADS is the most common syndrome associated with anti-MAG antibodies.
What is the response to corticosteroids or immunoglobulin in IgM-MGUS with anti-MAG neuropathy?
Little to no response.
What is the first-line drug for IgM-MGUS with anti-MAG neuropathy?
Rituximab.
What percentage of patients treated with rituximab achieve a good clinical response?
Need to clarify context of this question)
Less than 50% of cases.
What was the clinical outcome for patients treated with ibrutinib in a small case series for IgM anti MAG demyelinating PN?
Early and persistent clinical response.
What are the hallmark features of the chronic ataxia syndromes caused by IgM disialosyl antibodies (CANOMAD and CANDA)?
Pure sensory ataxia, areflexia, minimal motor involvement, with or without ophthalmoplegia.
CANDA = chronic ataxic neuropathy with anti-dialosyl IgM antibodies
The slide made me realize that CANOMAD and Miller Fisher syndrome are fairly similar other than the chronicity and IgM paraproteins.
What does the complete presentation of CANOMAD include?
Chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins, disialosyl antibodies.
What is absent in the incomplete form CANDA compared to CANOMAD?
External ocular muscles weakness and cold agglutinins.
What type of antibodies are frequently detected in the CANOMAD/CANDA?
Anti-ganglioside antibodies, especially against disialosyl-type epitopes (GD1b, GD3, GT1b, GQ1b).
Slowed CV are seen in most CANOMAD/CANDA but what percentage of patients may show normal motor conduction velocities with reduced amplitudes?
Up to 27% of patients.
So basically these conditions are typically demyelinating but 1/3 of patients can have axonal presentation
What is considered first-line therapies for CANOMAD/CANDA?
IVIG, Rituximab. Steroids produce no clinical benefit.
When is rituximab used in treatment?
Need to clarify context—-
Rituximab is used for patients refractory to immunoglobulin or with early symptom recurrence.
What is the typical type of monoclonal gammopathy light chains in POEMS?
Almost always lambda.
What acronym describes some systemic symptoms in POEMS?
PEST: Papilledema, Edema, Sclerotic bone lesions, Thrombocytosis.
What phenotype of neuropathy is associated with POEMS syndrome?
Sensorimotor, length-dependent, and demyelinating.
I guess this is similar to DADs except perhaps more motor involvement.
What are the NCS differences in neuropathy between POEMS syndrome and typical CIDP?
Less temporal dispersion, fewer conduction blocks in POEMS compared to typical CIDP (similar to DADS).
What is the most frequent endocrinopathy in POEMS syndrome?
Hypogonadism is the most frequent endocrinopathy in POEMS syndrome.
What is Castleman disease?
A lymphoproliferative disorder found in 11%-25% of POEMS patients.
What percentage of POEMS syndrome patients may have meningeal thickening?
70%-90% - so MRI brain can be helpful.
What percentage of POEMS syndrome cases have an elevated VEGF?
98%.
What is the treatment for POEMS patients with three or fewer bone lesions and no plasma cells on iliac crest biopsy?
Radiotherapy of the lesions. This leads to survival rate of >70% over 10 years and can lead to improvement in PN after several months.
What systemic treatment is necessary for POEMS patients with more than three bone lesions or plasma cells on bone marrow biopsy?
Autologous hematopoietic stem cell transplantation (HSCT). This can achieve 94% 5 yr survival but can take up to 3 years for max neurologic improvement.
What percentage of AL amyloidosis cases is the lambda light chain responsible for?
75%-80% of cases.
What percentage of AL-amyloidosis cases experience neuropathy?
One-third of cases experience neuropathy.
What percentage of AL-amyloidosis cases involve bilateral carpal tunnel syndrome?
Up to 21% of cases.
What type of neuropathy is associated with AL-amyloidosis?
Axonal, length-dependent neuropathy with sensory predominance.
In rare cases, what type of neuropathy can AL-amyloidosis manifest as?
Demyelinating neuropathy, similar to CIDP.
What are the 2 main red flags for AL-amyloidosis as the etiology to a CIDP like presentation?
Refractoriness to usual treatment and evident dysautonomia (dysautonomia is very rare in CIDP).
What are the main nerve fibers involved initially at the onset of peripheral neuropathy in AL-amyloidosis?
Involvement of small, unmyelinated fibers causing burning pain, thermo-algesic hypoesthesia, and/or dysautonomia. Large fiber involvement comes later.
What are less common patterns of peripheral neuropathy in AL-amyloidosis (less than PN) ?
1) Cranial nerve involvement
2) Mononeuritis multiplex
3) Lower limb radiculoplexopathy due to amyloidoma.
4) CIDP
What percentage of patients with wild-type ATTR cardiac amyloidosis have monoclonal gammopathy?
20% of patients with wild-type ATTR cardiac amyloidosis have monoclonal gammopathy (which is sometimes AL amyloidosis!).
Main biopsy sites for amyloid deposition?
Abdominal fat, bone marrow, salivary glands, and/or lips.
What are determining factors for favorable outcomes in AL-amyloidosis?
Early diagnosis and treatment. For this reason it is considered a ‘therapeutic emergency.’
What is neurolymphomatosis?
Invasion of malignant lymphoid cells in peripheral or central nervous systems.
What condition can myelomas lead to, affecting the spinal nerves?
Leptomeningeal myelomatosis, causing radiculopathy or cauda equina syndrome.
What is the most common pattern of neuropathy distribution in neurolymphomatosis?
Multiple mononeuropathies.
What other forms of neurolymphomatous neuropathy presentation are described besides multiple mononeuropathies?
Brachial Plexopathy
LS plexopathy
Cranial Neuropathy
Radiculopathy
What is the eponym of the condition where there is neoplastic infiltration of the nervous system in Waldenstrom’s macroglobulinemia?
Bing-Neel syndrome.
This commonly affects the CNS and can affect proximal nerve roots/cranial nerves.
What is the confirmatory diagnosis method for neurolymphomatosis?
Nerve biopsy - but be careful bc it can be patchy.
How can biopsy accuracy for neurolymphomatosis be improved?
Guided by MRI or PET-CT.
What diagnostic method helps identify clonal lymphocytes in cerebrospinal fluid in neurolymphomatosis patients?
Flow cytometry.
What mutation in CSF cytometry is highly suggestive of neurolymphomatosis?
MYD88 mutation. This is also common in Bing-Neel syndrome.
What should raise suspicion for neurolymphomatosis?
Presence of M-protein in patients with multiple mononeuropathy, plexopathy, or radiculopathy.
What type of neuropathy is associated with peripheral nerve involvement in cryoglobulinemia?
Distal sensory-motor neuropathy, symmetrical or mononeuritis multiplex pattern.
What symptoms are significant in peripheral nerve involvement in cryoglobulinemia?
Sensory symptoms and significant pain in distal limbs.
