Prospective and cross-sectional multicentre cohort study nerve sonography in polyneuropathy

A polyneuropathy is a prevalent disorder of the peripheral nerves, that has a
wide spectrum of underlying pathology. The starting point of diagnosing a
polyneuropathy, is to classify it as either axonal or demyelinating The
potential causes and treatments differ among axonal and demyelinating
polyneuropathies. The differentiation between axonal and demyelinating
polyneuropathies is at present based on clinical features and electrodiagnostic
studies. However, this diagnostic sensitivity of clinical and electrodiagnostic
findings is poor due to coinciding clinical presentations of the various
polyneuropathy subtypes and the modest discriminating power (sensitivity and
specificity) of electrodiagnostic studies. High resolution sonography (HRUS) of
the peripheral nervous system may have an additive value in this
discrimination. It evaluates nerve parameters different from electrodiagnostic
studies and has recently established its place in the diagnostic guidelines of
mononeuropathies. Current literature suggests, that in demyelinating
polyneuropathies HRUS reveals more abnormalities as compared to axonal
polyneuropathies. It was never studied, whether HRUS is of additional value to
clinical and electrodiagnostic parameters in discriminating axonal from
demyelinating polyneuropathy. Such a finding would have practical implications
for polyneuropathy diagnosis, and is the main objective of this study.

1.The first objective is to determine the nature and spatial distribution of
sonographic abnormalities in demyelinating and axonal polyneuropathies of
different etiologies.

2.On the basis of the findings in objective 1, we define a standardized HRUS
research protocol that has the highest discriminative value between
demyelinating and axonal polyneuropathies.

3.To determine whether this standardized HRUS protocol is of additional value
to clinical and electrodiagnostic parameters in discriminating axonal from
demyelinating polyneuropathies in a consecutive group of patients suspected of
polyneuropathy. If HRUS is of additional value, a prediction rule for
demyelinating polyneuropathy will be defined.

4.To evaluate whether the additive value of this prediction rule holds true in
common neurological practice, it is validated in a new cohort of consecutive
patients suspected of polyneuropathy.

To study objective 1, nerve sonography will be performed in clearly defined,
hereditary and acquired, demyelinating (chronic inflammatory demyelinating
polyneuropathy, Charcot-Marie-Tooth type 1, multifocal motor neuropathy (MMN),
hereditary neuropathy with liability to pressure palsies and anti-Mag
associated polyneuropathy) and axonal (chronic idiopathic axonal
polyneuropathy, spinal muscular atrophy, vasculitis associated polyneuropathy)
polyneuropathies. It will encompass extensive sonographic measurement in
multiple nerves in both arms and legs. Various sonographic parameters will be
evaluated (e.g. nerve and fascicle size, vascularisation). This study results
in a description of the nature and distribution of the sonographic
abnormalities for each of the investigated polyneuropathies.

To investigate objective 2, the demonstrated nature and spatial distribution of
the sonographic abnormalities will be further categorized. By selecting the
parameters and nerves with the highest discriminating power between axonal and
demyelinating polyneuropathies, the extensive HRUS protocol will be reduced to
a standardized HRUS protocol.

To evaluate objective 3, a group of consecutive patients clinically suspected
of a polyneuropathy (derivation set) will undergo clinical and
electrodiagnostic evaluation, as well as the standardized HRUS protocol. We
will determine whether this standardized HRUS protocol is of additional value
to clinical and electrodiagnostic parameters in discriminating axonal from
demyelinating polyneuropathies Since there is no gold standard for
polyneuropathy diagnosis, we will apply the use of consensus diagnosis as
outcome variable. Consensus diagnosis is based on combined clinical information
consisting of clinical presentation and course, treatment response in treated
cases, results from electrodiagnostic studies, analysis from blood and CSF,
nerve biopsy, family history and DNA analysis. If HRUS is of additional value,
a prediction rule for demyelinating polyneuropathy will be defined.

Finally, to study objective 4, the prediction rule will be tested in a
validation set in a prospective multicentre cohort study of consecutive
patients clinically suspected for polyneuropathy. Consensus diagnosis is used
as outcome variable, as mentioned under objective 3.

Clinical examination, laboratory results and electrodiagnostic studies are part
of the standard clinical evaluation of patients clinically suspected for
polyneuropathy. A short history and neurologic examination are standardized.
Nerve sonography is the only additional burden that is required for the purpose
of this study. This has proven to be safe, reliable, effective, non-invasive
and is usually well tolerated.