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the best combination of sensitivity and specificity27. normal parameters, which would enable a reliable dis
These criteria have since become the most widely used ease biomarker to be established, is difficult47. The over
in clinical research worldwide28, and their use is advis whelming consensus is that detection of demyelination
able in routine clinical practice, as the high sensitivity in semi-thin or ultra-thin sections is neither specific nor
minimizes the likelihood that the diagnosis of a treatable sensitive for CIDP48, particularly when attempting to
condition will be missed. distinguish CIDP from demyelinating hereditary poly
neuropathies49,50. Total T-cell and macrophage counts,
Cerebrospinal fluid analysis. Cerebrospinal fluid (CSF) which are markers of immune-mediated nerve damage,
protein levels are increased in most patients with CIDP. also have low sensitivity for CIDP diagnosis51,52, although
However, as protein levels can be normal in >50% of the presence of perivascular macrophage clusters has
atypical forms29, the precise global sensitivity of this been proposed as a valid criterion to differentiate inflam
marker is uncertain, although a figure as high as 95% matory neuropathy from other forms of neuropathy with
has been reported for typical forms30. However, a sub high sensitivity and specificity53. Some evidence suggests
stantial proportion of patients with diabetes — in par that other inflammatory markers, such as endoneurial
ticular, those with a longer disease duration — can have oedema or the activity of matrix metalloproteinase‑9
high levels of CSF protein31. Consequently, making a (MMP-9), in patients with diabetes and CIDP have
diagnosis of CIDP as opposed to another neuropathy higher diagnostic value54,55, but these studies were explor
in a patient with diabetes is challenging on the basis of atory, and the methods used are not widely available47.
CSF protein levels alone, although levels >1 g/l seem For peripheral neuropathology, the quality of the reports
to be exceptional in patients with diabetes unless they is highly dependent — more so than for other diagnostic
have CIDP18. Use of this value as a cut-off — which, for work-ups — on the availability of specialized laborato
similar reasons, has been proposed for distinguishing ries and expertise. The consensus among neuromuscular
between patients with Charcot–Marie–Tooth disease physicians is that a nerve biopsy is not needed for the
and those with Charcot–Marie–Tooth disease associated initial diagnosis of CIDP, as it is unlikely to provide a
with CIDP32 — might be helpful. conclusive answer. Nevertheless, the method might prove
helpful in cases of atypical CIDP48, for the exclusion of
Imaging. Various imaging techniques have been added differential diagnoses, and for further investigation when
to the diagnostic armamentarium for CIDP in the past patients do not respond to treatment.
15 years. Magnetic resonance neurography (MRN) might An alternative technique that has the potential to
aid the diagnosis of CIDP by enabling identification of aid diagnosis of CIDP is corneal confocal microscopy
nerve hypertrophy and/or hyperintensity33,34. Gadolinium (CCM), a noninvasive and rapid ophthalmological ima
enhancement on MRI, particularly in hypertrophied ging technique that can quantify axonal loss in a variety
nerve roots, might also contribute by indicating the pres of peripheral neuropathies56. CCM may be a viable surro
ence of an inflammatory process, as occurs in CIDP35. gate end point for early diagnosis of DSPN, stratification
Whether MRN might be useful for differentiating CIDP of patients with diabetes according to the severity of their
from other neuropathies in patients with diabetes is cur neuropathy, and assessment of response to treatment57,58.
rently unknown, particularly because several studies have In a cross-sectional study, patients with CIDP, multifocal
shown that MRN detects proximal lesions in patients with motor neuropathy, or neuropathy with MGUS (mono
DSPN36–38 — this observation raises doubts about the clonal gammopathy of undetermined significance) were
specificity of changes detected by MRN in patients with compared with healthy controls (in total, 182 patients
CIDP and diabetes, as opposed to diabetes alone. and controls were included). Reduced corneal nerve fibre
A study published in 2017 has shown that diffusion density, branch density and length were associated with
tensor imaging (DTI) MRN can identify nerve lesions Langerhans cell infiltration around corneal nerves (FIG. 1)
in patients with type 1 diabetes, reflecting proximal and and correlated with the degree of neurological deficits59.
distal nerve fibre pathology39. However, nerve abnormal Further longitudinal studies are required to determine
ities on DTI have also been described in CIDP40, and the utility of this technique for assessing progression of
further research is needed to determine whether the disease and response to treatment.
technique can distinguish between the two conditions.
Finally, ultrasound imaging has indicated that cross- Distinguishing CIDP
sectional nerve area enlargement is present in DSPN41,42 The challenge of determining whether a patient has CIDP
and CIDP43,44, and an association between nerve size and is greatest in patients with diabetes, because these indi
CIDP disease status has been reported45. Future stud viduals can have neurological deficits that resemble CIDP
ies might determine whether CIDP and DSPN can be phenotypes but are caused by other neuropathies. These
differentiated according to sites and patterns of nerve neuropathies can include the typical diabetic neuropathy,
size abnormalities. or the atypical inflammatory neuropathies. Here, we dis
cuss the features of these conditions, and how they can
Neuropathology. Early reports of CIDP emphasized be distinguished from CIDP in patients with diabetes.
the value of nerve biopsy findings46, but the relevance
of histology is currently a matter of debate among spe DSPN. DSPN is characterized by early involvement
cialists. As nerve biopsy is an invasive procedure, sam of small fibres, which leads to pain and dysaesthe
ples from healthy controls are rare, so establishing the sias1,4,60,61, and later involvement of large fibres, which
a b c
Figure 2 | Histopathological features in CIDP. a | Staining against CD3 with diaminobenzidine (DAB) reveals perivascular
T-cell infiltrates (brown) in the sural nerve of a patient with chronic inflammatory demyelinatingNature Reviews | Neurology
polyradiculoneuropathy
(CIDP); cell nuclei are counterstained with haematoxylin and appear blue (magnification 200x). b | In the endoneurium,
large numbers of CD68‑positive foamy macrophages can be seen with DAB staining (brown; magnification 200x).
c | Semi-thin nerve sections in CIDP reveal a large degree of myelin loss as well as thinning of the myelin (toluidine blue
staining, magnification 400x).
a diagnosis of CIDP, derived from characteristic fea universal feature, and sensory symptoms and weight
tures of CIDP, and elements that contradict a diagnosis loss are common. Panplexopathy is also common, as
of CIDP, derived from the characteristics of the axonal is contralateral spreading. Concurrent lumbosacral
neuropathy of DSPN (TABLE 1). or thoracic involvement occurs in 25% of cases. CSF
protein levels are mildly raised, and electrophysiology
Diabetic radiculoplexus neuropathies. Diabetic indicates axonal rather than demyelinating involvement.
radiculoplexus neuropathy (also known as dia Abnormal MRI findings, including increased T2 signals,
betic amyotrophy, Bruns–Garland syndrome or nerve hypertrophy and, in rare cases, contrast enhance
diabetic polyradiculoneuropathy) typically involves the ment, are common. As in the case of DLRPN, the disease
lumbosacral plexus80–82 or, less frequently, the cervical course is monophasic.
plexus, and usually occurs in middle-aged to elderly Diabetic radiculoplexus neuropathies can be difficult
men with type 2 diabetes83. The life-long incidence to distinguish from CIDP, particularly given the proxi
among patients with type 2 diabetes is ~1%84. Diabetic mal motor weakness and possible bilateral involvement.
lumbosacral radiculoplexus neuropathy (DLRPN) pre However, the acute presentation and the prominence of
sents with extreme unilateral thigh pain with weak pain in diabetic radiculoplexus neuropathy is not typical
ness, starting proximally and monolaterally, and often of CIDP, and is sufficient to enable a correct diagnosis. In
extending distally and contralaterally. Pain and sensory addition, the conduction slowing that can be observed
symptoms occur early, and weakness and muscle wasting in diabetic radiculoplexus neuropathy is not sufficient to
are long-term features of the condition. Weight loss is meet the stringent criteria for CIDP87.
common, and can be substantial. Upper-limb involve
ment can occur. DLRPN can also occur in a painless Vasculitic multiple mononeuropathies. Vasculitic
form, which is considered by some to be a ‘diabetic multiple mononeuropathy (also called mononeuritis
CIDP’, given that its onset is symmetrical and slower multiplex), which does not resemble the radiculoplexus
than that of DLRPN, and that the symptoms are more neuropathies, can occur in diabetes91. This condition
widespread and frequently involve the upper limbs85,86. presents with painful mononeuropathies that manifest
In a study of 23 patients with slowly progressive, pain in succession over days to weeks. The distinction of vas
less, symmetrical, motor-predominant neuropathy, culitic multiple mononeuropathies from CIDP is usually
nerve biopsy demonstrated a reduction in myelinated straightforward owing to the mononeuropathic pattern
fibre density with epineurial vessel wall inflammation and the acute and painful presentation, which are not
and microvasculitis87, similar to that seen in the typical features of CIDP.
painful form88,89. In both the painless and painful forms,
CSF protein levels are raised and electrophysiology can CIDP presenting as acute inflammatory neuropathy.
reveal mild conduction slowing. The disease course is The progressive course of CIDP distinguishes the condi
monophasic, and patients recover without treatment, tion from the acute inflammatory polyneuropathies, or
although the condition can last for up to 18 months80,82 Guillain–Barré syndrome, in which the nadir is reached
and recovery can take up to 3 years90. Multiple s tudies by week 4. However, ~15% of patients with CIDP can
have suggested that DLRPN has an autoimmune experience an acute onset that is indistinguishable from
basis, as indicated by the microvasculitis that has been that of Guillain–Barré syndrome92, although the subse
demonstrated pathologically88,89. quent relapsing or progressive course confirms the diag
Diabetic cervical radiculoplexus neuropathy nosis of CIDP93. The absence of a preceding infection,
(DCRPN) has similar characteristics to DLRPN 82. facial weakness, dysautonomia or a need for mechan
Onset is acute in most patients, pain is the presenting ical ventilation indicate CIDP, as does the presence of
symptom in >60% of patients, weakness is an almost sensory signs92,93.
Table 1 | Selected features of DSPN, CIDP and CIDP in patients with diabetes
Feature DSPN CIDP CIDP in patients with diabetes
Clinical • Early small-fibre involvement, pain, • Symmetrical proximal and distal muscle • Features of CIDP without diabetes
presentation dysaesthesia, numbness weakness, sensory loss to large-fibre • Older patients
• If autonomic neuropathy: tachycardia, modalities (vibration and proprioception) • Short duration of diabetes
orthostatic hypotension, gastroparesis, and reduced or absent reflexes9 • Good glycaemic control76
constipation, diarrhoea, erectile • Often greater motor than sensory deficits
dysfunction, neurogenic bladder and • Rapid progression over months (at least
sudomotor dysfunction1–4,60,61,157,158 8 weeks)
• Progression over years • Subgroups: focal and multifocal
asymmetric presentation, distal forms,
pure motor forms and pure sensory forms
Diagnostics • Electrophysiology: sensorimotor • Electrophysiology: high-sensitivity and • Electrophysiology: NCV to <70% of the
polyneuropathy, mild slowing of NCV high-specificity EFNS–PNS criteria met LLN, distal motor latency >150% of the
with normal latencies74,75 • Increased CSF protein levels are common ULN, and conduction block >50%, all in
• CSF protein levels might be slightly • MRN and ultrasound might be multiple nerves, highly specific; distal
elevated31 helpful in some cases for detecting compound muscle action potential
heterogeneously thickened and dispersion83,87–89
hyperintense nerves • CSF: not specific to distinguish from
• Sural nerve biopsy might be helpful DSPN, but levels >1 g/l are unusual in
in some cases for demonstrating diabetes32,159
inflammatory features47 • Sural nerve biopsy might be helpful
in some cases for demonstrating the
inflammatory features of CIDP47
Histology • Myelinated fibre loss • Demyelination and remyelination (onion • Epineurial perivascular T‑cell infiltrates
• Reduction in unmyelinated axon bulb formation) • Immunoreactivity for matrix
density and diameter • Endoneurial oedema and epineurial metalloproteinase‑9 (REF. 55)
• Increase in unassociated Schwann cell perivascular T‑cell infiltrates51,54
profile density
• Endoneurial microangiopathy (luminal
narrowing, endothelial cell hyperplasia
and hypertrophy, pericyte cell loss and
basement membrane thickening160–171)
Treatment • Symptomatic • Intravenous immunglobulin or • Corticosteroids to be avoided
• Improvement of glycaemic control corticosteroids as first-line therapy • Iintravenous immunoglobulin as first-line
might limit progression in type 1 • Plasma exchange118 therapy
diabetes, but has no effect in type 2 • Cyclophosphamide131,132 or rituximab133 • Plasma exchange118
diabetes in refractory disease • Cyclophosphamide131,132 or rituximab133
• No evidence to support use of in refractory disease
immunotherapy
CIDP, chronic inflammatory demyelinating neuropathy; CSF, cerebrospinal fluid; DSPN, distal symmetric peripheral neuropathy; EFNS–PNS, European Federation
of Neurological Societies–Peripheral Nerve Society; LLN, lower limit of normal; MRN, magnetic resonance neurography; NCV, nerve conduction velocity;
ULN, upper limit of normal.
APC Apoptosis
Schwann
T cell Macrophage cell
C5b–9
IFN-γ
TNF P0 P2 MBP
T cell TH1
IL-4
IL-6 Non-compact myelin
IL-10 Extracellular
TGF-β
Antibodies
B cell TH2
Intracellular
MAG Cx32 GLP
Figure 3 | Current model of immunopathogenesis in CIDP. The immune response in chronic inflammatory
Nature Reviewscells
demyelinating polyneuropathy (CIDP) involves cellular and humoral immune responses. Antigen-presenting | Neurology
(APCs),
such as dendritic cells or macrophages, activate autoreactive T cells. These T cells can cross the blood–nerve barrier
(BNB) to enter the peripheral nerve, a process mediated in part by chemokines, cellular adhesion molecules and
metalloproteinases (orange circles). In addition, T cells can activate B lymphocytes via secretion of cytokines, such as IL‑4
and IL‑6. Within the PNS, T cells are re‑exposed to the target antigen by local APCs (a macrophage is depicted), thereby
reactivating these cells and driving clonal expansion within the peripheral nerve. CD4+ T cells can differentiated into
T-helper 1 (TH1) cells, which, once activated by APCs, release pro-inflammatory cytokines and drive the inflammatory
process, or TH2 cells, which control and mitigate inflammation by secreting anti-inflammatory mediators. Macrophages
are predominantly activated by TH1 cells, and exhibit increased phagocytic activity, produce cytokines and release toxic
mediators, such as nitric oxide, that can directly damage Schwann cells and contribute to axonal damage. In addition,
pro-inflammatory cytokines, such as tumour necrosis factor (TNF) or IFNγ, are locally produced by B cells, and contribute
to demyelination and axonal damage. Antibodies can mediate demyelination by antibody-dependent cellular
cytotoxicity, can block epitopes that are functionally relevant to nerve conduction, and can activate the complement
system via the classical pathway, yielding pro-inflammatory mediators and the lytic C5b–9 terminal complex.
Termination of the inflammatory response is mediated, in part, by macrophages through induction of T-cell apoptosis
and release of anti-inflammatory cytokines, such as IL‑10 and transforming growth factor (TGF)-β. Myelin proteins, such
as P0, P2, myelin basic protein (MBP), myelin-associated glycoprotein (MAG), connexin 32 (Cx32) and glucagon-like
peptide (GLP), are putative target antigens in CIDP.
follow‑up of patients in this trial and in a previous retro were also observed with pulse therapy111. Long-term
spective study suggest that corticosteroids induce a treatment with any of these corticosteroids requires
higher remission rate and longer remission times than regular monitoring. For IVIg treatment, dosage require
IVIg109,110. Consequently, cautious use of corticosteroids ments are variable, and should be titrated to the minimal
might be considered, even for patients with diabetes and effective dose in each case. Treatment withdrawal trials
mild disease. should be considered at regular intervals112; trials can be
Options for corticosteroid therapy are oral attempted yearly, although the frequency depends on
dexamethasone pulse treatment, intravenous methyl individual patients’ circumstances.
prednisolone, or a daily oral regime of prednisolone. Response rates to treatment for CIDP are compa
Current evidence indicates that pulse therapy provides rable between patients with and without diabetes15,113.
faster onset of benefit and has a better safety profile than However, the benefit in patients with diabetes might
the other options111: pulse therapy has been associated be limited by underlying DSPN85. Indeed, more-severe
with significantly lower rates of sleeplessness and moon baseline axonal loss predicts a poor treatment response114.
facies. In a comparison of pulse therapy with daily oral Efforts to identify electrophysiological predictors of
regimens, a significantly lower risk of weight gain >3 kg treatment response in CIDP initially yielded negative
and a near-significant reduced risk of raised blood sugar results115, although a report published in 2015 suggested
All participants had experienced proximal and dis analysis has suggested that untreated patients even
tal limb weakness for 4–12 months before their initial tually improve to a similar degree to those receiving
examination, and all were treated with IVIg. Neuropathy IVIg or plasma exchange148. Furthermore, the clinical
Impairment Scores improved for 14 patients (87.5%), descriptions of some patients who responded to treat
and mean summated conduction velocities improved in ment imply that they had CIDP rather than DLRPN149.
the upper and lower limbs, although motor and sensory Descriptions of the same treatment being ineffective also
axonal loss progressed. contradict the positive findings150. Owing to these uncer
The largest study to date is a retrospective compara tainties, no evidence base supports any treatment for
tive analysis of 134 patients with CIDP: 67 with diabetes diabetic radiculoplexus neuropathies, particularly con
and 67 without diabetes113. In this analysis, the diagnosis sidering that corticosteroids impair glycaemic c ontrol in
of CIDP was based on expert opinion and use of diagnos this population151.
tic criteria that did not include electrophysiological meas Distinguishing CIDP from microvasculitis can be dif
ures145, and were previously found to be highly specific ficult87, but in practice, patients for whom either diagno
but less sensitive than the EFNS–PNS criteria for CIDP27. sis is reasonable should be considered to have CIDP and
Assessment of response was based on a combination of treated accordingly. A proportion of patients with clini
physician and patient evaluations, including the Toronto cally typical CIDP without diabetes do not fulfil electro
Clinical Neuropathy Score (TCNS). Patients with CIDP physiological criteria for demyelination27,145, so denying
and diabetes had significantly higher TCNSs and a these patients treatment is inappropriate. Furthermore,
greater extent of proximal weakness than those without the technical expertise required for an adequate diag
diabetes, but significantly fewer of these patients received nostic neuropathology report greatly limits the use of
treatment (57% versus 93%, P <0.0001). No overall dif nerve biopsies in this urgent setting, so the clinical and
ference was seen in the responses to treatment with electrophysiological findings are often relied on to make
IVIg, corticosteroids, plasma exchange, azathioprine or a therapeutic decision. Nevertheless, the possibility of
mycophenolate mofetil, although the patients with dia monophasic disease must be kept in mind to avoid
betes were less likely to respond to IVIg (52%, compared unnecessary overtreatment and therapeutic escalation152.
with 87% for patients without diabetes, P <0.0001). In
the whole cohort, only a shorter duration of neuropathy Vasculitic multiple mononeuropathy. If vasculitic mul
had a favourable influence on response; age, the pres tiple mononeuropathy is suspected, an exhaustive diag
ence or duration of diabetes, the severity of neuropathy, nostic work‑up for vasculitic neuropathy is indicated,
and the degree of axonal loss had no impact. Besides its and if the work‑up is negative, nerve biopsy — preferably
retrospective design, this study was limited by the fact to sample a clinically affected sensory nerve — should
that validated functional scales for evaluation of CIDP, be performed for pathological confirmation of vasculitic
such as the Overall Neuropathy Limitations Scale and multiple mononeuropathy. Patients with and without
the Inflammatory Rasch-Built Overall Disability Score, diabetes should receive identical treatment for proven
were not used, the possibility that cases of DLRPN were or probable vasculitic multiple mononeuropathy, which
misclassified as CIDP because electrophysiology was is the same as the treatment for nonsystemic vasculitic
not mandatory for diagnosis, and the possibility of neuropathy without diabetes153.
selection bias owing to the relatively low treatment rate
among patients with CIDP and diabetes. Also of note, the Conclusions and practice implications
response rate among the 67 patients with CIDP without The most common neuropathy in patient with diabetes
diabetes — selected from a cohort of 1,950 people with is DSPN, but other neuropathies — including radiculo
CIDP to be age-matched and sex-matched to the patients plexus neuropathies, vasculitic multiple mononeuro
with diabetes — was higher than that reported in a pre pathies and CIDP — can occur and must be diagnosed
vious therapeutic trial146, but was comparable to the rate because they require different treatment approaches.
reported for treatment-naive patients with CIDP147. DLRPN and DCRPN are generally easy to recognize,
although they can be painless and extensive, making
Managing other inflammatory neuropathies their identification more difficult. The course of these
Radiculoplexus neuropathies. Treatments for painful conditions is monophasic, and the prognosis is generally
DLRPN and DCRPN are mainly symptomatic. No evi favourable.
dence currently indicates a benefit of immunotherapy CIDP is the most treatable neuropathy that can occur
for these conditions in diabetes83, and trials might be in diabetes. The frequency of CIDP among patients with
difficult to conduct owing to the heterogeneity of the diabetes remains controversial, but the rapidly progres
presentation. For patients who have extreme pain that sive disability caused by CIDP warrants awareness among
is refractory to analgesics, intravenous steroids could be health-care professionals of the association and the
considered in selected cases, but do not seem to hasten potential for immunomodulatory therapy. The diagnosis
recovery of strength83. Small case series, including fewer of CIDP in diabetes is primarily made clinically, and elec
than 20 patients in total, have suggested that IVIg is trophysiological measurements in CIDP with diabetes
beneficial, but no evidence has been generated in ran are less straightforward than in CIDP without diabetes.
domized controlled trials83. Similarly, case series indicate Nevertheless, currently recommended cut-offs for demy
that plasma exchange is beneficial, but these studies also elination remain highly specific for CIDP in patients with
included fewer than 20 patients in total. Comparative diabetes9. No diagnostic criteria offer perfect sensitivity,
however, and even when criteria are not fulfilled, a high rate to IVIg in patients with CIDP is uncertain, but this
clinical suspicion of CIDP warrants a treatment trial, treatment remains the most appropriate first-line ther
especially if the neuropathy is disabling. In the absence apy, particularly because it avoids the risk of worsening
of widely available, adequately interpreted nerve his glycaemic control that is associated with corticosteroids.
tology, this approach seems to be a pragmatic way to In future, a biomarker for CIDP might provide the
prevent patients missing out on effective treatment. To much-needed diagnostic certainty required for earlier
avoid unnecessarily prolonged immunotherapy, regular intervention, especially in patients with diabetes, for
monitoring, followed by reduction and withdrawal of whom diagnostic confirmation could be more helpful
treatment if necessary, is highly advisable, particularly in and earlier intervention more beneficial. Novel anti
patients with diabetes, because these individuals have an bodies against nodal proteins have been identified in
elevated risk of thromboembolism. The frequency of the CIDP in the past few years154–156, and these discoveries
treatment review can be decided on a case‑by-case basis, provide encouragement with regard to biomarker identi
but should be at least yearly. fication, although the antibodies identified apply only to
Response rates to treatment for CIDP seem to be a small proportion of patients with CIDP. Histology per
similar in patients with and without diabetes, although formed on skin and nerve biopsy samples is one imaging
underlying DSPN will limit the response, and full nor biomarker approach, but is impractical in routine clinical
malization of function and strength might not occur. practice55. Corneal confocal microscopy might be use
Nevertheless, neurologists should not be deterred from ful for identifying corneal axonal loss and infiltration of
attempting and escalating treatment as they would for Langerhans cells in CIDP59, but longitudinal studies are
patients with CIDP without diabetes. Treatment rates required to assess the effects of CIDP therapy on these
for CIDP in patients with diabetes are low113, indicating markers. In the meantime, increased awareness, detailed
that these individuals are frequently denied potentially and repeated clinical evaluation, adequate interpretation
effective treatment. Early treatment is advisable because of electrophysiology, and appropriate and timely con
delaying immunotherapy can reduce its effectiveness. sideration of therapeutic options remain essential in the
Whether the presence of diabetes reduces the response routine care of patients with CIDP and diabetes.
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endoneurial microvessels and sural nerve pathology Y.A.R., B.C.K and R.M. researched data for and wrote the H.-P.H. has received fees for consulting, speaking and serving
in diabetic neuropathy. Neurology 37, 20–28 article. All authors made substantial contributions to discus- on steering committees from Baxelta, CSL Behring, Kedrion,
(1987). sion of the content and reviewed and/or edited the Novartis, Octapharma and LfB. R.A.M. has received honor
168. Malik, R. A. et al. Microangiopathy in human manuscript before submission. aria for speaking or consultancy from Pfizer, Lilly and
diabetic neuropathy: relationship between capillary Novo Nordisk.
abnormalities and the severity of neuropathy. Competing interests statement
Diabetologia 32, 92–102 (1989). Y.A.R. has received speaker and/or consultancy honoraria Publisher’s note
169. Malik, R. A. et al. Endoneurial capillary from CSL Behring, LfB, Grifols, BPL, Octapharma and Springer Nature remains neutral with regard to jurisdictional
abnormalities in mild human diabetic neuropathy. Kedrion, has received educational sponsorships from LfB, claims in published maps and institutional affiliations.
J. Neurol. Neurosurg. Psychiatry 55, 557–561 CSL Behring and Baxter, and has obtained research grants
(1992). from CSL Behring and LfB. M.S. has received honoraria for Review criteria
170. Said, G., Goulon-Goeau, C., Slama, G. & consulting or lecturing and travel expenses for attending A search for original English-language, full-text articles was
Tchobroutsky, G. Severe early-onset polyneuropathy meetings from Biogen Idec, Genzyme, Novartis, Sanofi performed in PubMed using the search terms “chronic inflam-
in insulin-dependent diabetes mellitus. A clinical and Aventis, UCB, Grifols and TEVA, and has received financial matory demyelinating polyneuropathy”, “CIDP”, “demyelinat-
pathological study. N. Engl. J. Med. 326, 1257–1263 support for research from Bayer Health Care and UCB. B.C.K. ing neuropathy”, “diabetes”, “diabetic neuropathy”, “diabetic
(1992). has received honoraria for lecturing, travel expenses for proximal amyotrophy”, “diabetic cervical radiculoplexus
171. Dyck, P. J. et al. Capillary number and percentage attending meetings, and financial support for research from neuropathy” and “diabetic lumbar radiculoplexus neuro
closed in human diabetic sural nerve. Proc. Natl Acad. Bayer Health Care, Biogen, Genzyme/Sanofi Aventis, Grifols, pathy”. The reference lists of identified papers were searched
Sci. USA 82, 2513–2517 (1985). Merck Serono, Mitsubishi Europe, Novartis, Roche, Talecris for further relevant articles.