Objectives
To evaluate, in a prospective study, high-resolution ultrasound (HRUS) changes of nerve segments in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and their relationships ...with clinical and electrodiagnostic (EDX) characteristics.
Methods
Twenty-three consecutive patients with CIDP were included in a 3-year follow-up (FU) study. Each patient underwent neurologic examination, EDX and HRUS study. HRUS was performed on median, ulnar and peroneal nerves, yielding a total of 319 scanned nerve segments. INCAT and MRC-sum scores, motor nerve conduction velocity (NCV), compound muscle action potential (cMAP) amplitude, and nerve cross-sectional area (NCSA) were collected at baseline and at FU end, and were used for statistical analysis. Twenty-two healthy individuals, matched to patients for age and BMI, served as controls.
Results
NCSA was higher in patients than in controls (
p
< 0.0001) and showed significant direct correlation with disease severity, and inverse correlation with NCV and cMAP amplitude, both at baseline and at FU end. Disease duration, clinical scores and EDX were predictors of NCSA enlargement at both time points. During FU, NCSA increased in 51% of nerve segments (
p
= 0.006), in correlation with INCAT increase and with NCV and cMAP reduction. Considering EDX changes in subgroups that reflect the different types of nerve damage, NCSA significantly increased in those nerve segments that from normal EDX switched to prevalent myelinopathic EDX characteristics.
Conclusions
Peripheral nerve size tends to increase over time in patients with CIDP, in correlation with clinical and EDX changes, in particular in those nerve segments that undergo a predominantly demyelinating damage.
Aim
Study of intraepidermal nerve fiber density (IENFD) by skin biopsy represents a promising tool in the evaluation of patients with ATTRv polyneuropathy (ATTRv-PN). Herein, we retrospectively ...analyze intraepidermal innervation and quantitative sensory test (QST) data from an Italian cohort of Italian ATTRv-PN patients and asymptomatic carriers aimed to provide insights into early nerve pathological and functional changes in this disease.
Methods
IENFD and QST data of 14 ATTRv-PN patients and 14 asymptomatic carriers were retrospectively analyzed together with clinical and paraclinical data such as disease stage and severity, neuropathic pain scales, and sural SNAP amplitude.
Results
Given an estimated time to the predicted age of onset of symptomatic disease of 20.27 + / − 7.9 years, small nerve fiber loss seems to be unexpectedly early in carriers. Moreover, carriers showed skin denervation at the proximal (thigh) site, suggesting a non-length-dependent neuropathic process. IENFD at ankle correlated with disease severity and other paraclinical variables such as sural nerve potential amplitude and QST parameters. Patients at earlier stages of the disease did not show significant differences in ankle IENFD compared with asymptomatic carriers, but significant differences in terms of QST parameters, small fiber neuropathy symptoms, and neuropathic pain.
Conclusions
Skin biopsy can disclose an early non-length-dependent small fiber loss in ATTRv-PN and, together with QST, could provide a useful insight disease onset and progression.
Introduction
Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) remains a diagnostic challenge due to clinical, neurophysiological, and laboratory findings suggestive of other ...diagnoses, particularly chronic inflammatory demyelinating polyneuropathy (CIDP). In this cross-sectional prospective study, we aimed to investigate the utility of high-resolution ultrasonography of peripheral nerves as a diagnostic tool to differentiate ATTRv-PN from CIDP.
Methods
In 11 treatment-naive patients with genetically confirmed late-onset ATTRv-PN and 25 patients with CIDP, we collected clinical, electrodiagnostic, and high-resolution ultrasonography data of the peripheral nerves. In each patient, we used high-resolution ultrasonography to assess 26 nerve sites.
Results
Of the 11 patients with ATTRv-PN, two had electrodiagnostic study data compatible with a CIDP diagnosis. High-resolution ultrasonography showed that the cross-sectional area of the brachial plexus, median nerve at the axilla, arm, and forearm, ulnar nerve at the forearm, and peroneal nerve at the popliteal fossa were significantly smaller in the 11 ATTRv-PN patients than in CIDP patients. However, in the two patients with electrodiagnostic study data compatible with a CIDP diagnosis, high-resolution nerve ultrasonography data were comparable to those in patients with CIDP.
Conclusion
Although high-resolution ultrasonography of peripheral nerves provides reliable information in patients with ATTRv-PN, its usefulness as a standalone diagnostic tool to differentiate ATTRv-PN from CIDP might be limited.
Objectives
Immune-mediated necrotizing myopathy (IMNM) is the most severe idiopathic inflammatory myopathy (IIM) and early aggressive poly-immunotherapy is often required to reduce long-term ...disability. The aim of this study is to investigate muscle MRI in IMNM as outcome measure for disease activity, severity, progression, response to treatment, and to better characterize the pattern of muscle involvement.
Methods
This is a retrospective, observational, cross-sectional, and longitudinal study including 22 IMNM patients, divided into three groups based on timing of first MRI and if performed before or under treatment. T1 score and percentage of STIR positive muscles (STIR%) were considered and analyzed also in relation to demographic, clinical and laboratory characteristics.
Results
STIR% was higher in untreated patients and in those who performed MRI earlier (
p
= 0.001). Pelvic girdle and thighs were in general more affected than legs. T1 score was higher in patients with MRI performed later in disease course (
p
= 0.004) with a prevalent involvement of the lumbar paraspinal muscles,
gluteus medius
and
minimus
,
adductor magnus
and hamstrings. 22% of STIR positive muscles showed fat replacement progression at second MRI. Higher STIR% at baseline correlated with higher risk of fat replacement at follow-up (
p
= 0.003); higher T1 score correlated with clinical disability at follow-up, with late treatment start and delayed treatment with IVIG (
p
= 0.03).
Interpretation
Muscle MRI is a sensitive biomarker for monitoring disease activity and therapy response, especially when performed early in disease course and before treatment start, and could represent a supportive outcome measure and early prognostic index in IMNM.
Background and purpose
Cardiac involvement is observed in about 80% of subjects with myotonic dystrophy type 1 (DM1) and is mainly characterized by cardiac conduction and/or rhythm abnormalities ...(CCRAs), possibly leading to sudden cardiac death (SCD). Our objective was to investigate whether the gender difference may influence the cardiac involvement and SCD in DM1.
Methods
We analyzed prevalence and incidence of cardiological abnormalities in males versus females in 151 consecutive DM1 patients over a 35‐year follow‐up period.
Results
Fifty‐five patients, 35 males (62.5%) and 20 females (42.5%), developed some type of CCRA during the follow‐up period (mean 7.82 ± 6.21 years). CCRA overall, and specifically cardiac conduction abnormalities (CCAs), were significantly more frequent in males than in females (p = 0.043 and p = 0.031, respectively). CCRAs progressed in 16 males (45.7%) and six females (30%). Twenty‐four patients, 14 males (25.0%) and 10 females (21.3%), died during the follow‐up. Nine of them, six males (10.7%) and three females (6.4%), had SCD. After correction for Muscular Impairment Rating Scale progression, cytosine thymine‐guanine expansion, and follow‐up duration, a higher prevalence of CCAs was independently associated with male gender (p = 0.039), but independent association with gender was not detected for CCRAs overall, cardiac rhythm abnormalities, and SCD prevalence, even if prevalence was higher in males than females.
Conclusions
The overall risk of occurrence of CCAs in DM1 is significantly higher in males than females regardless of genetic background and disease severity and progression. Moreover, the data also suggest a similar impact for male gender for CCRAs overall, CCAs, and SCD even if not statistically significant.
The overall risk of cardiac abnormalities in myotonic dystrophy type 1 is significantly higher in males regardless of genetic background and disease severity and progression.
Introduction
Myasthenia gravis-inflammatory myopathy (MG-IM) association has been rarely reported as specific clinical entity characterized by variable myositis manifestations, ranging from ...subclinical to diffuse muscle involvement with characteristic distal upper limb weakness. Although, in view of this, it has been hypothesized that distal muscle weakness in MG-IM could be due to the muscle inflammation instead of a pure neuromuscular transmission impairment, a biopsy-proven myositis process of distal muscles of upper limbs has not yet been provided.
Methods
We report on clinical, immunological, and myopathological characterization of a novel case affected by MG-IM association showing the typical distal upper limb weakness, including muscle biopsy of a weak forearm muscle.
Results
Histological and immunohistochemical studies showed a marked inflammatory process on muscle biopsy of
extensor digitorum communis.
The patient, a 47-year-old man with 10-year history of anti-acetylcholine receptor (AChR) and anti-titin antibody-positive MG with thymoma, developed a progressive, diffuse, and non-fatigable weakness predominant in distal upper limb muscles, unresponsive to acetylcholinesterase inhibitors associated to myalgia and creatine kinase (CK) elevation.
Discussion
We provide the histopathological evidence of a prominent inflammatory process responsible of distal upper limb weakness in MG-IM association. Muscle biopsy does not reveal any typical histopathological feature of other nosologically definite inflammatory myopathy, leading MG-IM association to come close to the group of overlap-myositis (OM) with the myopathological features of non-specific myositis (NSM).
Objective
X-linked myopathy with excessive autophagy (XMEA) linked to the
VMA21
gene leads to autophagy failure with progressive vacuolation and atrophy of skeletal muscles. Current knowledge of this ...rare disease is limited. Our objective was to define the clinical, radiological, and natural history of XMEA.
Methods
We conducted a retrospective study collecting clinical, genetic, muscle imaging, and biopsy data of XMEA patients followed in France and reviewed the literature for additional cases.
Results
Eighteen males had genetically confirmed XMEA in France, carrying four different
VMA21
variants. Mean age at disease onset was 9.4 ± 9.9 (range 1–40) years. In 14/18 patients (77.8%), onset occurred during childhood (< 15 years); however in four patients, the disease started in adulthood. Patients had anterior and medial compartment thigh muscle weakness, distal contractures (56.3%), elevated CK levels (1287.9 ± 757.8 U/l) and autophagic vacuoles with sarcolemmal features on muscle histopathology. Muscle MRI (
n
= 10) showed a characteristic pattern of lower limb muscle involvement. In 11 patients, outcome measures were available for an average follow-up period of 10.6 ± 9.8 years and six of them show disease progression. Mean change of functional outcomes was 0.5 ± 1.2 points for Brooke and 2.2 ± 2.5 points for Vignos score, 7/16 patients (43.8%) needed a walking aid and 3/16 (18.8%) were wheelchair-bound (median age of 40 years old, range 39–48). The variant c.164-7 T > G was associated with a later onset of symptoms. Respiratory insufficiency was common (57.1%) but cardiac involvement rare (12.5%).
Interpretation
XMEA has variable age of onset, but a characteristic clinical, histopathological, and muscle imaging presentation, guiding the diagnosis. Although slowly, motor disability progresses with time, and relevant genotype–phenotype correlations will help design future clinical trials.
Introduction
Muscle ultrasound is a fast, non-invasive and cost-effective examination that can identify structural muscular changes by assessing muscle thickness and echointensity (EI) with a ...quantitative analysis (QMUS). To assess applicability and repeatability of QMUS, we evaluated patients with genetically confirmed facioscapulohumeral muscular dystrophy type 1 (FSHD1), comparing their muscle ultrasound characteristics with healthy controls and with those detected by MRI. We also evaluated relationships between QMUS and demographic and clinical characteristics.
Materials and methods
Thirteen patients were included in the study. Clinical assessment included MRC sum score, FSHD score and The Comprehensive Clinical Evaluation Form (CCEF). QMUS was performed with a linear transducer scanning bilaterally
pectoralis major
,
deltoid
,
rectus femoris
,
tibialis anterior
and
semimembranosus muscles
in patients and healthy subjects. For each muscle, we acquired three images, which were analysed calculating muscle EI by computer-assisted grey-scale analysis. QMUS analysis was compared with semiquantitative 1.5 T muscle MRI scale.
Results
All muscles in FSHD patients showed a significant increased echogenicity compared to the homologous muscles in healthy subjects. Older subjects and patients with higher FSHD score presented increased muscle EI.
Tibialis anterior
MRC showed a significant inverse correlation with EI. Higher median EI was found in muscles with more severe MRI fat replacement.
Conclusions
QMUS allows quantitative evaluation of muscle echogenicity, displaying a tight correlation with muscular alterations, clinical and MRI data. Although a confirmation on larger sample is needed, our research suggests a possible future application of QMUS in diagnosis and management of muscular disorders.
Background
Only a few studies have reported muscle imaging data on small cohorts of patients with myotonic dystrophy type 1 (DM1). We aimed to investigate the muscle involvement in a large cohort of ...patients in order to refine the pattern of muscle involvement, to better understand the pathophysiological mechanisms of muscle weakness, and to identify potential imaging biomarkers for disease activity and severity.
Methods
One hundred and thirty‐four DM1 patients underwent a cross‐sectional muscle magnetic resonance imaging (MRI) study. Short tau inversion recovery (STIR) and T1 sequences in the lower and upper body were analyzed. Fat replacement, muscle atrophy and STIR positivity were evaluated using three different scales. Correlations between MRI scores, clinical features and genetic background were investigated.
Results
The most frequent pattern of muscle involvement in T1 consisted of fat replacement of the tongue, sternocleidomastoideus, paraspinalis, gluteus minimus, distal quadriceps and gastrocnemius medialis. Degree of fat replacement at MRI correlated with clinical severity and disease duration, but not with CTG expansion. Fat replacement was also detected in milder/asymptomatic patients. More than 80% of patients had STIR‐positive signals in muscles. Most DM1 patients also showed a variable degree of muscle atrophy regardless of MRI signs of fat replacement. A subset of patients (20%) showed a ‘marbled’ muscle appearance.
Conclusions
Muscle MRI is a sensitive biomarker of disease severity alsofor the milder spectrum of disease. STIR hyperintensity seems to precede fat replacement in T1. Beyond fat replacement, STIR positivity, muscle atrophy and a ‘marbled’ appearance suggest further mechanisms of muscle wasting and weakness in DM1, representing additional outcome measures and therapeutic targets for forthcoming clinical trials.
We refined the pattern of muscle involvement in DM1 by upper and lower body muscle magnetic resonance imaging (MRI), identifying the most frequent pattern of fat replacement and confirming that muscle MRI is a sensitive biomarker of disease burden in DM1. We also observed: STIR‐positive muscles in 80% of patients preceding fat replacement, muscle atrophy in muscles unreplaced by fat, and progeroid muscle appearance supporting a premature muscle senescence. Our findings provide novel insights into the pathophysiological mechanisms of muscle wasting and weakness in DM1, and could represent additional outcome measures and therapeutic targets for forthcoming clinical trials.
Sixty-six patients with possible or probable MSA (multiple system atrophy) cerebellar type, personally observed between 2006 and 2018 were retrospectively reviewed. The time point of data collection ...was January 1, 2019. Forty-nine patients lost independent walking after a median time of 5 years (95% C. I. 4–6). Thirty-two patients were confined to wheelchair after a median time of 7 years (95% C. I. 7–8). Twenty-seven patients were deceased after a median time of 9 years (95% C. I. 8–10). A later onset predicted an earlier loss of independent walking (HR 1.07; 95% C.I. 1.03–1.11;
p
= 0.001). Higher UMSARS score predicted shorter time to loss of independent walking (HR 1.04; 95% C.I. 1.02–1.06;
p
= 0.001) and to wheelchair (HR 1.03; 95% C.I. 1.01–1.06;
p
= 0.021). No predictor of time to death was found.
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