15018752330
发表时间:2015-11-18 浏览次数:606次
Introduction
Multifocal motor neuropathy (MMN) is an intriguing peripheral nerve disease with a prevalence of 1-2/100,000 adults. Several diagnostic criteria have been proposed, mainly summarizing the
slowly progressive, asymmetric weakness, with a striking predilection
for the upper extremities, whereas sensory fibers and upper motor neuron
involvement fail in the disease course. Although the detection of conduction block remains the
electrophysiological hallmark of the disease, it is important to
recognize that it may not be possible to demonstrate this finding even
after careful studies, because blocks may be activity-dependent, and the
site of pathology may be very proximal in the brachial plexus or nerve
root level.
The first papers defined conduction block as a 20-30% amplitude or area
reduction in the distal compound muscle action potential (CMAP) if the
CMAP duration did not exceed 15% greater than normal. Computer modeling
of conduction block and temporal dispersion in an animal model has
demonstrated that up to 50% area reduction of the proximal to distal
CMAP can be due entirely to interphase cancellation. Similar studies in
human have shown that distal CMAP duration and proximal CMAP duration
prolongation are important factors for the definition of conduction
block in the median nerve segment over the forearm: the shorter the
distal duration and proximal duration prolongation the less CMAP
amplitude reduction is needed to diagnose a conduction block. The association between MMN and immunoglobulin M (IgM) antiganglioside
GM1 (anti-GM1) antibodies have already been suggested in the literature,
however, the diagnostic accuracy of anti-GM1 testing in diagnosing MMN
is unclear. The literature reports the presence of anti-GM1 IgM
antibodies in between 30% and 80% of MMN patients.
Meanwhile, neuromuscular ultrasound is an easily applicable and safe
method for studying structural changes in peripheral nerves. Various
ultrasound studies have reported pathological ultrasound changes in MMN
patients, reporting consistently an asymmetric, inhomogenous increase of
the nerve cross-sectional area (CSA). Three studies have reported controversial findings on the correlation
between sonographic and electrophysiological results in MMN patients. In view of the severe functional disability of MMN patients, it remains
unknown that of these two methods could better highlight the functional
and clinical status of these patients.
The aim of this review is to provide a timely update on the role of the neuromuscular ultrasound in the diagnostic of the MMN.
Quantification of nerve ultrasound findings
Cross-sectional area reference values for peripheral nerves and brachial plexus have been already reported in the literature. The difficulty, however, to differentiate normal from a pathologic
heterogeneity of CSA changes in peripheral nerves, especially in cases
of immune-mediated neuropathies, remains an important limitation of the
neuromuscular ultrasound in clinical application. CSA enlargement can be
the result either of edema (usually accompanied by disturbed fascicular
echostructure) or hypertrophy (usually accompanied by preserved
fascisular echostructure).
Novel ultrasound measures, aiming to
quantify pathologic ultrasound changes of peripheral nerves in
immune-mediated polyneuropathies, have been recently introduced in the
literature:
(1) the intranerve CSA variability (for each nerve), defined as maximal
CSA/minimal CSA; (2) the internerve CSA variability (for each patient),
defined as nerve with maximal intranerve CSA variability/nerve with
minimal intranerve CSA variability; (3) the side to side difference
ratio of the intranerve CSA variability (for each nerve), defined as
side with maximal intranerve CSA variability/side with minimal
intranerve CSA variability; and (4) the intraplexus CSA variability
defined as maximal CSA of the brachial plexus/minimal CSA of the
brachial plexus [Table 1].
Using the intranerve CSA variability, the sonographer may
differentiate a focal (higher values) from diffuse (lower values) nerve
hypertrophy while the internerve CSA variability may reveal possible
distribution patterns of peripheral nerve impairment. On the other hand, the side to side difference ratio of the intranerve
CSA variability may be useful in detecting any lateralization of
pathologic changes and the intraplexus CSA variability in
differentiating focal (higher values) from diffuse (lower values)
brachial plexus hypertrophy.
Results
Currently, 6 studies (evaluating a total of 55 cases) of nerve sonography in MMN patients have been published [Table 2]. The first description of pathological ultrasound findings in MMN was published by Beekman et al. In this report, the authors documented at least one anatomical site with pathological hypertrophy of the median or ulnar or radial nerves and/or brachial plexus in 90% of the cases. The authors concluded that the neuromuscular ultrasound may allow the detection of pathological signs to a greater extent than nerve conduction tests in MMN. In a later study of 12 MMN patients, nerve hypertrophy was documented in the median (forearm), ulnar (Guyons' canal, forearm, elbow, upper arm) and tibial nerve (ankle), but not in brachial plexus, when compared to controls [Figure 1] and [Figure 2].
Considering the morphology of peripheral nerve hypertrophy (focal vs. diffuse), Padua et al. have reported the inhomogenous CSA enlargement, mainly of the median, ulnar and fibular nerve in a small group of MMN patients. A second study on two MMN patients not only confirmed the focal type of CSA enlargement, but also documented the significant lateralization of ultrasound findings. Another MMN study has documented a focal type of CSA enlargement in the median nerve, when compared with controls. In addition, the higher values of the internerve CSA variability and "side to side difference ratio of the intranerve CSA variability'' of the median, ulnar and fibular nerve, were attributed by the authors to the possible striking predilection of MMN to certain peripheral nerves and the asymmetry of findings respectively.
A possible explanation for the CSA enlargement in MMN cases could derive
from pathological studies at sites of conduction blocks. According to
these studies, perivascular areas contain scattered demyelinated axons,
which are often surrounded by small onion bulb formations. These onion bulb formation may lead to a consecutive CSA enlargement of
the nerve. In addition, pathological CSA changes are usually detected
at several proximal and distal sites in the anatomic course of the
peripheral nerves in MMN patients. This finding may reflect the
immune-mediated patchy multifocal demyelination occurring along the
motor nerve fibers in this type of immune-mediated injury.
Another important aspect in the field of sonography in MMN is the
possible use of this method for identifying nerve conduction blocks. The
localization of the nerve conduction block is often difficult to be
identified in the nerve conduction studies (NCS), especially when
dealing with proximal parts of the nerves. By overlooking the
electrophysiological hallmark of the disease, delay in the diagnosis and
therefore delayed treatment can occur. Beekman et al. documented pathological ultrasound findings not only at sites with
electrophysiological impairment, but also at sites with normal
functioning in NCS. An absolute correlation between site of nerve
hypertrophy and site of conduction block has been reported only in one
case in the literature.
Another study on 12 MMN patients showed a significant correlation
between sonographic and electrophysiological findings only between the
CMAP and CSA of the median nerve at the upper arm.
Systematic prospective studies on the sensitivity of ultrasound in
detecting focal immune-mediated nerve lesions fail in the literature.
An
interesting point of future study is the applicability of the nerve
ultrasound as screening method for immune-therapy in dysimmune
neuropathies. Nerve ultrasound and NCS failed to highlight functional
disability in post-Guillain-Barré syndrome and chronic inflammatory
demyelinating polyneuropathy patients in the literature. In a later study on MMN patients, neither sonography nor
electrophysiology correlated with the Medical Research Council sum
score, Rasch-built Overall Disability Scale score or Rasch-built fatigue
severity scale. These studies have shown that the already known ultrasound biomarkers
(CSA, echogenity, intranerve CSA variability) are not able to highlight
the effectivity of immune-therapy.
Conclusion
To summarize, the currently available ultrasound studies show that
mainly a focal type of asymmetrical peripheral nerve enlargement is
expected in MMN. Nerve ultrasound findings seem to show no significant
correlation to electrophysiological findings at most anatomical sites.
In addition, prospective studies on the applicability of ultrasound as
screening method of immune-therapy fail in the literature, while various
retrospective studies failed to highlight any significant correlation
between ultrasound findings and functional disability.
As the
main uncertainties regarding the diagnostic criteria of MMN are steadily
resolved, new challenges continuously arise on how to acquire the best
static and dynamic imaging of the relevant nerve structures in this type
of immune-mediated disease, aiming to provide a complementary and
holistic approach to nerve impairment. The first nerve ultrasound
studies on MMN have shown that ultrasound seems to be a reliable and
easily applicable method to detect pathological structural changes in
peripheral nerves. The quantification of ultrasound changes and
highlighting the distribution patterns of pathological findings remains a
challenging aspect of future study. The recently proposed measurements
in the literature may help to achieve this goal, but multicentre
prospective validation is needed.
References
1.Mahdi-Rogers M, Hughes RA. Epidemiology of chronic inflammatory neuropathies in southeast England. Eur J Neurol 2014;21:28-33.
2.Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. 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;15:295-301.
3.Nodera H, Bostock H, Izumi Y, Nakamura K, Urushihara R, Sakamoto T, Murase N, Shimazu H, Kusunoki S, Kaji R. Activity-dependent conduction block in multifocal motor neuropathy: magnetic fatigue test. Neurology 2006;67:280-7.
4.Pakiam AS, Parry GJ. Multifocal motor neuropathy without overt conduction block. Muscle Nerve 1998;21:243-5.
5.Delmont E, Azulay JP, Giorgi R, Attarian S, Verschueren A, Uzenot D, Pouget J. Multifocal motor neuropathy with and without conduction block: A single entity? Neurology 2006;67:592-6.
6.Beekman R, van den Berg LH, Franssen H, Visser LH, van Asseldonk JT, Wokke JH. Ultrasonography shows extensive nerve enlargements in multifocal motor neuropathy. Neurology 2005;65:305-7.
7.Padua L, Martinoli C, Pazzaglia C, Lucchetta M, Granata G, Erra C, Briani C. Intra-and internerve cross-sectional area variability: New ultrasound measures. Muscle Nerve 2012;45:730-3.
8.Kerasnoudis A. Correlation of sonographic and electrophysiological findings in a patient with multifocal motor neuropathy. J Neuroimaging 2014;24:305-7.
9.Kerasnoudis A, Klasing A, Behrendt V, Gold R, Yoon MS. Intra-and internerve cross-sectional area variability: New ultrasound measures. Muscle Nerve 2013;47:146-7.
10.Kerasnoudis A, Pitarokoili K, Behrendt V, Gold R, Yoon MS. Multifocal motor neuropathy: correlation of nerve ultrasound, electrophysiological and clinical findings. J Peripher Nerv Syst 2014;19:165-74.
11.Kerasnoudis A, Yoon MS. The role of neuromuscular ultrasound in the diagnostic of immune-mediated neuropathies. In: Brown MO, Budd BA, editors. Advances in Neuropathy Research. New York: Nova Science Publishers; 2013. p. 119-33.
12.Kerasnoudis A, Pitarokoili K. Ulnar nerve reference values for cross-sectional area, intranerve cross sectional area variability and side to sid difference ratio. Rheumatol Int 2014;34:551-2.
13.Kerasnoudis A, Pitarokoili K, Behrendt V, Gold R, Yoon MS. Cross sectional area reference values for sonography of peripheral nerves and brachial plexus. Clin Neurophysiol 2013;124:1881-8.
14.Zaidman CM, Harms MB, Pestronk A. Ultrasound of inherited vs. acquired demyelinating polyneuropathies. J Neurol 2013;260:3115-21.
15.Kaji R, Oka N, Tsuji T, Mezaki T, Nishio T, Akiguchi I, Kimura J. Pathological findings at the site of conduction block in multifocal motor neuropathy. Ann Neurol 1993;33:152-8.
16.Kerasnoudis A, Pitarokoili K, Behrendt V, Gold R, Yoon MS. Correlation of nerve ultrasound, electrophysiological and clinical findings in chronic inflammatory demyelinating polyneuropathy. J Neuroimaging 2014. doi: 10.1111/jon. 12079.
17.Kerasnoudis A, Pitarokoili K, Behrendt V, Gold R, Yoon MS. Correlation of nerve ultrasound, electrophysiological, and clinical findings in post Guillain-Barré syndrome. J Peripher Nerv Syst 2013;18:232-40.