Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Neuromuscular Medicine > Paraproteinemic Neuropathies > Flashcards

Paraproteinemic Neuropathies Flashcards

(78 cards)

Start Studying
1
Q
A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is a paraproteinaemic neuropathy?

A

Peripheral nerve injury caused by a monoclonal immunoglobulin (paraprotein) from a clonal B-cell or plasma cell disorder.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe the clinical spectrum of paraproteinaemic neuropathies.

A

Ranges from small-fiber sensory dysfunction to disabling sensorimotor deficits, acute to chronic, indolent to rapidly progressive.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Name the main haematological disorders associated with paraproteinaemic neuropathy.

A

MGUS, multiple myeloma, Waldenström macroglobulinaemia, non-Hodgkin lymphoma, POEMS syndrome, AL amyloidosis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What types of paraproteins exist?

A

Complete immunoglobulins (IgG, IgM, IgA) or free light chains (κ or λ).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Define MGUS.

A

Monoclonal gammopathy of undetermined significance: M-protein <3 g/dL, bone marrow plasma cells <10%, no end-organ damage.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the annual progression risk of MGUS to malignancy?

A

~1% per year to multiple myeloma or lymphoproliferative disorders.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the prevalence of paraproteins by age?

A

3–4% >50 y, up to 8–9% >90 y.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What proportion of idiopathic neuropathies have a paraprotein?

A

Approximately 10%.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which paraprotein class is most often causal in neuropathy?

A

IgM (31% develop neuropathy), vs 14% IgA, 6% IgG.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How does patient age affect the significance of a paraprotein?

A

<55 y: usually pathologic; >70 y: low-titre paraprotein with normal SFLC often incidental.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

List the antibodies associated with nerve injury.

A

Anti-MAG/SGPG, anti-ganglioside (GM1/GD1b), anti-disialosyl in CANOMAD.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How does deposition cause neuropathy?

A

Tissue deposition of misfolded light chains (AL amyloid) or IgM crystals leads to axonal degeneration.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe cytokine-mediated neuropathy.

A

VEGF-driven microangiopathy in POEMS; inflammatory vasculitis in cryoglobulinaemia.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is infiltrative nerve injury?

A

Direct invasion of nerves by malignant cells (neurolymphomatosis, Bing-Neel syndrome).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Give examples of ischaemic mechanisms.

A

Vasculitis (cryoglobulinaemia), hyperviscosity-related infarcts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

When does compressive neuropathy occur?

A

Extrinsic compression by plasmacytomas or amyloid deposits.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Name treatment-related neuropathies.

A

Bortezomib, thalidomide, vincristine, other neurotoxic chemotherapies.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

When should you investigate neuropathy for paraprotein?

A

Typical syndrome, unexplained neuropathy + paraprotein, haematological disorder + neuropathy, incidental paraprotein + symptoms.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the role of SPEP?

A

Quantifies M-protein if >0.5 g/L; low sensitivity for small clones.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Why use serum immunofixation?

A

Detects ≥0.1 g/L paraprotein, types Ig class; gold standard for detection.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What does urine immunofixation detect?

A

Bence Jones proteins (free light chains); sensitivity ~38%.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Interpret the SFLC κ:λ ratio.

A

Normal 0.26–1.65; ratio >1.65 or <0.26 suggests clonality (affected by renal function).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Why perform bone marrow biopsy?

A

Plasma cell percentage, clonality, Congo red for amyloid, cytogenetics (e.g., MYD88 L265P).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What is a cryoglobulin assay for?
Detects immunoglobulins that precipitate <37 °C; types I–III guide diagnosis.
26
When measure serum viscosity?
Suspected hyperviscosity (IgM WM); values >4 centipoise indicate risk.
27
Neurophysiological hallmark of anti-MAG neuropathy?
Uniform distal slowing, terminal latency index <0.25, no conduction blocks.
28
Neurophysiology in POEMS?
Demyelination in upper limbs, axonal loss in lower limbs, absent lower-limb SNAPs.
29
Neurophysiology in AL amyloid?
Small-fiber predominant; abnormal QSART/QST; possible mild conduction slowing.
30
Neurophysiology in MMN?
Conduction blocks in motor nerves, normal sensory studies.
31
What are typical CSF findings?
Elevated protein (>1 g/L in demyelinating cases; often >3 g/L in POEMS), acellular, flow cytometry if lymphoma suspected.
32
MRI uses in paraproteinaemic neuropathy?
Plexus/nerve root thickening (POEMS, neurolymphomatosis); leptomeningeal enhancement (Bing-Neel).
33
What does PET-CT show in neurolymphomatosis?
FDG uptake in infiltrated nerves (SUVmax >3.5) for neurolymphomatosis.
34
Which biopsy is first-line for amyloid?
Abdominal fat pad aspiration (75% sensitivity) stained with Congo red.
35
When is salivary gland or nerve biopsy needed?
If fat pad is negative but clinical suspicion for amyloid or lymphoma infiltration remains.
36
Anti-MAG pathophysiology?
IgM binding to MAG/SGPG on Schwann cells disrupts myelin, causing segmental demyelination (“dying-back”).
37
Anti-MAG clinical features?
Distal paresthesias, sensory ataxia, high-frequency tremor, late distal weakness.
38
How to diagnose anti-MAG neuropathy?
ELISA anti-MAG >70,000 BTU, uniform distal slowing on NCS, no conduction blocks.
39
Treatment of anti-MAG neuropathy?
Rituximab 375 mg/m² weekly ×4; emerging ibrutinib (BTK inhibitor).
40
Characteristics of non-MAG IgM demyelinating neuropathy?
Similar to anti-MAG but no known antigen; monitor if mild, treat clone if progressive.
41
MMN pathophysiology & features?
IgM anti-GM1/GD1b causes motor conduction block; presents with asymmetric distal weakness, cramps, fasciculations.
42
MMN treatment?
IVIg loading (2 g/kg) then maintenance (1 g/kg monthly); immunosuppression if refractory.
43
CANOMAD triad?
Chronic sensory ataxia, ophthalmoplegia, IgM anti-disialosyl antibodies.
44
CANOMAD pathophysiology?
IgM against GD1b/GT1b depletes gangliosides at nodes of Ranvier → sensory ganglionopathy.
45
CANOMAD diagnosis & treatment?
CSF high protein, anti-GD1b ELISA; IVIg for flares, rituximab ± cyclophosphamide maintenance.
46
How is IgM deposition disease diagnosed?
Nerve biopsy with electron microscopy showing endoneurial IgM crystals.
47
Describe Bing-Neel syndrome infiltration pattern.
Waldenström cells infiltrate leptomeninges, nerve roots, sometimes parenchyma.
48
Bing-Neel clinical & diagnostic features?
Headaches, seizures, cranial and peripheral neuropathies; MRI enhancement, CSF flow cytometry, MYD88 L265P.
49
Bing-Neel treatment?
Ibrutinib (560 mg daily), intrathecal methotrexate, CNS-penetrating chemo.
50
POEMS mandatory and additional criteria?
Mandatory: polyneuropathy + monoclonal λ plasma cell disorder; plus ≥1 major (Castleman’s, sclerotic lesions, VEGF >1000 pg/mL) and ≥1 minor (organomegaly, edema, endocrinopathy, skin changes, papilloedema, thrombocytosis/polycythaemia).
51
POEMS neuropathy pattern?
Subacute painful sensorimotor neuropathy, distal weakness > sensory, calf pain common.
52
POEMS diagnostics (VEGF, imaging)?
Serum VEGF >1000 pg/mL; MRI plexus/root thickening, pachymeningeal enhancement; skeletal survey for sclerotic lesions.
53
POEMS treatment?
Local radiotherapy for ≤2 lesions; disseminated disease: autologous HSCT, lenalidomide + dexamethasone, daratumumab in trials.
54
When does multiple myeloma cause neuropathy?
Rare (<3%); usually secondary to cryoglobulinaemia, amyloid, therapy, or compression.
55
Stages of AL amyloid neuropathy?
1) Small-fiber + carpal tunnel; 2) Autonomic dysfunction; 3) Cardiac/renal failure.
56
AL amyloidosis biopsy sites & staining?
Fat pad (75%), labial salivary gland (86%), nerve if needed; Congo red → apple-green birefringence; mass spectrometry for typing.
57
AL amyloid treatment?
HSCT if eligible; bortezomib SC + dexamethasone; tafamidis for concurrent ATTRv.
58
Neurolymphomatosis clinical patterns?
Type 1 painful asymmetric mononeuritis multiplex (68%), Type 2 CIDP-like symmetric polyneuropathy (34%).
59
Neurolymphomatosis imaging & biopsy?
MRI nerve/plexus enhancement (80%), PET-CT SUVmax>3.5; nerve biopsy shows perivascular CD20+ infiltrates.
60
Neurolymphomatosis treatment?
R-CHOP + intrathecal cytarabine/methotrexate; CAR-T for refractory cases.
61
Cryoglobulinaemia types & features?
Type I monoclonal (IgM>IgG) – hyperviscosity, skin necrosis, small-fiber neuropathy; Type II mixed – vasculitis, HCV; Type III polyclonal – CTD/infection.
62
Cryoglobulinaemia management?
Cold avoidance, plasmapheresis, rituximab, corticosteroids, treat underlying disease.
63
Hyperviscosity syndrome features & management?
Mucosal bleeding, visual/hearing changes, ataxia, stroke; treat with emergency plasma exchange then clone-directed therapy.
64
Key electrodiagnostic distinctions: CIDP vs anti-MAG vs POEMS?
CIDP: conduction blocks/dispersion; anti-MAG: uniform distal slowing, no blocks; POEMS: proximal demyelination + distal axonal loss.
65
Why is serum immunofixation mandatory in neuropathy work-up?
SPEP and SFLC miss up to 20% of small paraprotein clones; immunofixation detects ≥0.1 g/L.
66
Which neurological markers should you monitor?
INCAT or QMT scores q3–6 mo, quantitative sensory testing for small fibers.
67
Which haematological markers should you monitor?
M-protein level, SFLC ratio, VEGF in POEMS, cryocrit in cryoglobulinaemia.
68
Give examples of emerging BTK inhibitor uses.
Ibrutinib in anti-MAG and Bing-Neel; zanubrutinib in Bing-Neel (NCT04116437).
69
What is the “MAGic Tremor” mnemonic?
Anti-MAG neuropathy presents with distal sensory loss + high-frequency tremor.
70
What does the POEMS mnemonic stand for?
Peripheral neuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes.
71
What pitfall relates to MGUS by age?
Paraprotein in <55 y likely pathologic; in >70 y with low titre and normal SFLC often incidental.
72
What are the red-flag features for AL amyloid neuropathy?
Non-diabetic autonomic dysfunction + carpal tunnel syndrome → early biopsy.
73
How do you calculate the terminal latency index (TLI)?
TLI = distance to muscle (mm) ÷ (motor conduction velocity × distal latency). A TLI <0.25 suggests anti-MAG.
74
What three factors define high‐risk MGUS in the Mayo Clinic model?
Non-IgG isotype, M-protein ≥15 g/L, abnormal SFLC ratio outside 0.26–1.65.
75
What NT-proBNP cutoff stratifies cardiac stage in AL amyloidosis?
NT-proBNP >1,800 ng/L defines stage III disease (worse prognosis).
76
Describe the apple-green birefringence of amyloid on biopsy.
Congo-red–stained tissue under polarized light shows apple-green glow due to β-pleated sheets.
77
MRI features of POEMS neuropathy?
Brachial/lumbosacral plexus thickening, diffuse nerve root enhancement, pachymeningeal enhancement.
78
How do you distinguish temporal dispersion from conduction block on NCS?
Temporal dispersion = prolonged, broadened CMAP without ≥50% amplitude drop; conduction block = ≥50% drop in proximal vs distal CMAP amplitude.

Neuromuscular Medicine (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions