A comparative study of CIDP in a cohort of HIV-infected and HIV-uninfected patients
K Moodley, FCN (South Africa) VB Patel, PhD (South Africa)
Department of Neurology, University of KwaZulu-Natal, Durban, South Africa
Table e-1: Characteristics of the 10 CIDP patients with Type 2 Diabetes Mellitus
M=male,F=female,I=Indian,B=black,IVIg=intravenous immunoglobulin,AZA=azathiaprine
Table e-2: Mean functional scores in the HIV-infected and HIV-uninfected categories
Functional Scores / median; IQR / median;IQR / PVPresentation
INCAT Score in UL / 3; 0-2 / 3;2-4 / 0.27
INCAT Score in LL / 4;0-4 / 3;2-4 / 0.02
ODSS Score in UL / 4.5;2-4 / 4;2-4 / 0.29
ODSS Score in LL / 5;4-6 / 4;3-5 / 0.06
6 months
INCAT Score in UL / 0;0-2 / 2;0-3,75 / 0.004
INCAT Score in LL / 1;0-3 / 3;1-4 / <0.0001
ODSS Score in UL / 1; 0-2 / 2 ;1-4 / 0.0004
ODSS Score in LL / 2; 0-2 / 3;0-5 / 0.0002
12 months
INCAT Score in UL / 0;0-1 / 1;0-3 / 0.0005
INCAT Score in LL / 0.5;0-2 / 3;1-4 / <0.0001
ONLS Score in UL / 0;0-2 / 3;0-5 / <0.0001
ONLS Score in LL / 1;0-3 / 3;1-5 / 0.0002
18 months
INCAT Score in UL / 0;0-1,5 / 1.5;0-1,5 / <0.0001
INCAT Score in LL / 0;0-2 / 2,1-4 / <0.0001
ODSS Score in UL / 0;0-1 / 2;1-5 / 0.0001
ODSS Score in LL / 0.63;0-2 / 3;1-5 / <0.0001
IVIG=intravenous immunoglobulin, INCAT= Inflammatory Neuropathy Cause and Treatment Scale, ODSS=Overall disability Sum Score, UL=Upper Limb, LL=Lower Limb
Table e-4: Characteristics of patients requiring combination therapy in the HIV-infected category
Patient / Duration of Disease (months) / On ARVs at presentation / CD4 count at presentation / Viral load at presentation / Denervation on EMG1 / 12 / Yes / 610 / undetectable / 2+
2 / 24 / Yes / 960 / undetectable / 2+
3 / 9 / Yes / 766 / undetectable / 1+
4 / 10 / yes / 1226 / undetectable / 2+
5 / 12 / Yes / 812 / undetectable / 3+
Figure-1: Time to respond to first line therapy
Figure e-2: Time to Remission in the HIV-infected and HIV-uninfected categories
Management Protocol for CIDP in the Neurology Department at IALCH
The current management protocol for CIDP in our unit is corticosteroids as first line therapy for all patients regardless of their HIV status. IVIG is only used if corticosteroids are contraindicated. Combination therapy or other immunosuppressant therapy (including IVIG) is added for the following reasons:
1)if patients do not respond to first line treatment in the first 3 to 6 months,
2)if they continue to deteriorate on first line monotherapy,
3)if they have side effects to treatment and if they develop corticosteroid dependence and require a corticosteroid sparing agent.
Definitions:
Corticosteroid responsiveness:
Objective clinical improvement within 3-6 months to corticosteroids at a dose of 1mg/kg/day.
IVIG responsiveness:
Clinical improvement within 3-6 months of IVIG therapy administered monthly for 3-6 months, the first course given for 5 days at a dose of 0.4g/kg/day and thereafter a 0,4g/kg infusion over one day every month.
Remission:
Maintenance of the best clinical response (that is being relapse free with no clinical progression of disease or deterioration of functional scores) on lowest possible dose of therapy or no treatment at all.
Lack of efficacy:
No clinical improvement within 3-6 months or deterioration within the first 3 months of therapy.
EFNS/PNS Electrodiagnostic criteria1
(1) Definite: at least one of the following:
(a) Motor distal latencyprolongation ≥50% above ULN in two nerves (excluding median neuropathy at the wrist from carpal tunnel syndrome), or,
(b) Reduction of motor conduction velocity ≥30% below LLN in two nerves, or
(c) Prolongation of F-wave latency ≥30% above ULN in two nerves (≥50% if amplitude of distal negative peak CMAP <80% of LLN values), or
(d) Absence of F-waves in two nerves if these nerves have distal negative peak CMAP amplitudes ≥20% of LLN + ≥1 other demyelinating parameter in ≥ 1 other nerve, or
(e) Partial motor conduction block: ≥50% amplitude reduction of the proximal negative peak CMAP relative to distal, if distal negative peak CMAP ≥ 20% of LLN, in two nerves, or in one nerve + ≥1 other demyelinating parameter in ≥1 other nerve, or
(f) Abnormal temporal dispersion (>30% duration increase between the proximal and distal negative peak CMAP) in ≥2 nerves, or
(g) Distal CMAP duration (interval between onset of the first negative peak and return to baseline of the last negative peak) increase in ≥1 nerve (median ≥ 6.6 ms, ulnar ≥ 6.7 ms, peroneal ≥ 7.6 ms, tibial ≥ 8.8 ms) + ≥1 other demyelinating parameter in ≥1 other nerve
(2) Probable: ≥30% amplitude reduction of the proximal negative peak CMAP relative to distal, excluding the posterior tibial nerve, if distal negative peak CMAP ≥20% of LLN, in two nerves, or in one nerve + ≥1 other demyelinating parameter in ≥1 other nerve
(3) Possible: As in (1) but in only one nerve
To apply these criteria, the median, ulnar (stimulated below the elbow), peroneal (stimulated below the fibular head), and tibial nerves on one side are tested.
If criteria are not fulfilled, the same nerves are tested at the other side, and/or the ulnar and median nerves are stimulated bilaterally at the axilla and at Erbs point.
Motor conduction block is not considered in the ulnar nerve across the elbow and at least 50% amplitude reduction between Erbs point and the wrist is required for probable conduction block. Temperatures should be maintained to at least 33 degrees C at the palm and 30 degrees C at the external malleolus (good practice points).
CMAP, compound muscle action potential; ULN, upper limit of normal values; LLN, lower limit of normal values.
(1) Inclusion criteria(a) Typical CIDP chronically progressive, stepwise, or recurrent symmetric proximal and distal weakness and sensory dysfunction of all extremities, developing over at least 2 months; cranial nerves may be affected; and absent or reduced tendon reflexes in all extremities
(b) Atypical CIDP (still considered CIDP but with different features):
One of the following, but otherwise as in (a) (tendon reflexes may be normal in unaffected limbs):
i)Predominantly distal (distal acquired demyelinating symmetric) or multifocal acquired demyelinating sensory and motor neuropathy (MADSAM),
ii)Lewis–Sumner syndrome
iii)Pure motor or Pure sensory
(2) Exclusion criteria
Borrelia burgdorferi infection (Lyme disease),
diphtheria,
drug or toxin exposure
Hereditary demyelinating neuropathy
Prominent sphincter disturbance
Diagnosis of multifocal motor neuropathy
IgM monoclonal gammopathy with high titre antibodies to myelin-associated glycoprotein
Other causes for a demyelinating neuropathy including POEMS syndrome,
osteosclerotic myeloma,diabetic and non-diabetic lumbosacral radiculoplexus neuropathy.
PNS lymphoma and amyloidosis
EFNS/PNS Clinical Criteria 1
EFNS/PNS Supportive Criteria 1
1. Elevated CSF protein with leukocyte count <10/mm3 (level A recommendation)
INCAT Disability Scale 2
Arm disability
0No upper limb problems
1Symptoms, in one or both arms, not affecting the ability to perform any of the following functions: doing all zips and buttons; washing or brushing hair; using a knife and fork together; handing small coins
2Symptoms, in one arm or both arms, affecting but not preventing any of the above mentioned functions
3Symptoms, in one arm or both arms, preventing one or two of the above mentioned functions
4Symptoms, in one arm or both arms, preventing three or all of the functions listed, but some purposeful movements still possible
5Inability to use either arm for any purposeful movement
Leg disability
0Walking not affected
1Walking affected, but walks independently outdoors
2Usually uses unilateral support (stick, single crutch, one arm) to walk outdoors
3Usually uses bilateral support (sticks, crutches, frame, two arms) to walk outdoors
4Usually uses wheelchair to travel outdoors, but able to stand and walk a few steps
with help
5Restricted to wheelchair, unable to stand and walk a few steps with help
Overall disability results fromsum of arm and leg disability scores
Overall Disability Sum Score (ODSS) 3
Arm disability scale – function assessed as; not affected, affected but not prevented, or,prevented – in respect of the following:
Dressing upper part of body (excluding buttons/zips)
Washing and brushing hair
Turning a key in a lock
Using knife and fork (/spoon—applicable if the patient never uses knife and fork)
Doing/undoing buttons and zips
Arm graded as:
0 = Normal
1 = Minor symptoms or signs in one or both arms but not affecting any of the functions listed
2 = Moderate symptoms or signs in one or both arms affecting but not preventing any of the functions listed
3 = Severe symptoms or signs in one or both arms preventing at least one but not all functions listed
4 = Severe symptoms or signs in both arms preventing all functions listed but some purposeful movements still possible
5 = Severe symptoms and signs in both arms preventing all purposeful movements
Leg disability scale – assessed as; ‘yes’, ‘no’,or,’ Not applicable’
Do you have any problem with your walking?
Do you use a walking aid?
How do you usually get around for about 10 metres?
Without aid
With one stick or crutch or holding to someone’s arm
With two sticks or crutches or one stick or crutch and holding to someone’s arm
With a wheelchair
If you use a wheelchair, can you stand and walk a few steps with help?
If you are restricted to bed most of the time, are you able to make some
purposeful movements?
Leg grade
0 = Walking is not affected
1 = Walking is affected but does not look abnormal
2 = Walks independently but gait looks abnormal
3 = Usually uses unilateral support to walk 10 metres (25 feet) (stick, single crutch, one arm)
4 = Usually uses bilateral support to walk 10 metres (25 feet) (sticks, crutches, two arms)
5 = Usually uses wheelchair to travel 10 metres (25 feet)
6 = Restricted to wheelchair, unable to stand and walk few steps with help but able to make some purposeful leg movements
7 = Restricted to wheelchair or bed most of the day, preventing all purposeful movements of the legs (eg, unable to reposition legs in bed)
Overall disability sum score = arm disability scale (range 0–5) + leg disability scale (range 0–7); overall range: 0 (no signs of disability) to 12 (maximum disability).
For the arm disability scale: allocate one arm grade only by completing the function checklist. Indicate whether each function is “affected,” “affected but not prevented,” or “prevented.”
For the leg disability scale: Allocate one leg grade only by completing the functional questions.
References:
- Joint Task Force of the E, the PNS. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society--First Revision. J Peripher Nerv Syst 2010;15:1-9.
- Hughes R, Bensa S, Willison H, et al. Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol 2001;50:195-201
- Merkies ISJ , Clinimetric evaluation of a new overall disability scale in immune mediated neuropathies, JNNP, 2002;72:596-601