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.
Abstract Introduction Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease characterized by myotonia and progressive muscular weakness and atrophy. The aim of this study was to ...investigate the usefulness of longitudinal muscle MRI in detecting disease activity and progression in DM1, and to better characterize muscle edema, fat replacement and atrophy overtime. Materials and methods This is a prospective, observational, longitudinal study including 25 DM1 patients that performed at least two muscle MRIs. Demographic and genetic characteristics were recorded. Muscular Impairment Rating Scale (MIRS) and MRC score were performed within 3 months from MRIs at baseline (BL) and at follow-up (FU). We analysed 32 muscles of lower body (LB) and 17 muscles of upper body (UB) by T1 and STIR sequences. T1-, STIR- and atrophy scores and their variations were evaluated. Correlations between MRIs’ scores and demographic, clinical and genetic characteristics were analysed. Results Eighty (80%) of patients showed fat replacement progression at FU. The median T1 score progression (ΔT1-score) was 1.3% per year in LB and 0.5% per year in UB. The rate of fat replacement progression was not homogenous, stratifying patients from non-progressors to fast progressors (> 3% ΔT1-score per year). Half of the STIR-positive muscles at BL showed T1-score progression at FU. Two patients with normal MRI at baseline only showed STIR-positive muscle at FU, marking the disease activity onset. STIR positivity at baseline correlated with fat replacement progression (ΔT1-score; p < 0.0001) and clinical worsening at FU (ΔMRC-score; p < 0.0001). Sixty-five (65%) of patients showed STIR- and fat replacement-independent muscle atrophy progression, more evident in UB. Conclusions Muscle MRI represents a sensitive biomarker of disease activity, severity, and progression in DM1. STIR alterations precede fat replacement and identify patients with a higher risk of disease progression, while T1-sequences reveal atrophy and fat replacement progression before clinical worsening.
Objective
To test the complement inhibitor eculizumab in the treatment of MG exacerbation during therapy with the immune-checkpoint inhibitor (ICI) pembrolizumab, avoiding its discontinuation, which ...could be detrimental to oncologic course.
Methods
A 76-year-old male with non-thymomatous generalized anti-AchR + MG (MGFA class IVB), during treatment with pembrolizumab for colorectal cancer, developed a severe myasthenic exacerbation, refractory to steroids and IvIg. Eculizumab was started, without pembrolizumab discontinuation. The patient was prospectively followed using MGFA, MG Activities of Daily Living (MG-ADL), Quantitative MG (QMG), MG Composite (MGC), and MG Quality of Life 15 (MG-QOL-15).
Results
After an 18-week follow-up, the patient presented a progressive improvement in scores on all scales, achieving a MGFA class IIIB. The percentage improvement was 40% in MG-ADL, 36% in MG Composite, and about 30% in QMG. Bulbar symptoms improved by about 70% in MG-ADL and MG Composite and 40% in QMG. Eculizumab was well tolerated and pembrolizumab regularly continued, with a good control of cancer progression.
Discussion
Eculizumab potentially offers a mechanism-based treatment of MG in patients under anti-programmed cell death protein 1 (PD-1) agents, without interfering with their mechanism of action and avoiding their discontinuation. Larger case series deserve to be evaluated.
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.
Introduction
Mitochondrial alterations are a common finding in muscle biopsy of sporadic inclusion body myositis (s-IBM) and polymyositis with mitochondrial pathology (PM-Mito). Both disorders ...generally have poor treatment response. Nevertheless, mitochondrial myopathology has been rarely reported in dermatomyositis (DM) outside areas of perifascicular atrophy and a relationship with therapeutic outcome is not established.
Methods
We report on clinical, immunological, radiological, and myopathological findings of a case of severe, treatment-refractory anti-Mi-2-positive DM.
Results
A 77-year-old woman developed anti-Mi-2 DM with severe diffuse muscle weakness associated with abundant mitochondrial abnormalities at muscle biopsy, beside the typical features of inflammatory myopathy. The patient was poorly responsive to multiple-line therapies and finally anti-JAK (anti-Janus activated kinase) was administered, leading to partial clinical improvement.
Discussion
Given the usual satisfactory treatment response and favorable outcome of anti-Mi-2 DM, we suppose that mitochondrial dysfunction on muscle biopsy could represent a marker of disease severity in DM, predicting a worse response to treatment and a poor clinical outcome. JAK-inhibitors could represent a good treatment option in refractory anti-Mi-2 DM with mitochondrial abnormalities.
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).
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.
