This monocentric prospective study of patient suffering from Amyotrophic lateral sclerosis (ALS) aims to evaluate the prognosis and diagnostic potential of both Neurofilament-Light (Nf-L) and ...neuroinflammatory biomarkers in serum and CSF. Candidate markers levels were measured using multiplex method in serum of 60 ALS patients, 94 healthy controls of 43 patients suffering from Inflammatory Peripheral Neuropathies (IPN). A comparative CSF analysis was performed for 20 ALS and 17 IPN patients. Among the altered biomarkers, CSF Nf-L level remains the best marker of ALS severity, while serum levels correlate strongly with disease progression. The combination of Nf-L and ICAM-1 concentrations in the CSF and IFN-γ concentration in the serum differentiate ALS patients from IPN patients with improved sensibility and specificity relative to individual biomarkers. A cutoff value of 0.49 for the fitted values of these 3 biomarkers discriminate ALS from IPN patients with a specificity of 100% (78.20-100%) and a sensibility of 85.71% (57.19-98.22%) with an AUC of 0.99 ± 0.01. The measure of Nf-L and neuroinflammatory biomarkers in CSF and serum can be useful biomarkers panel in the differential diagnosis of ALS.
Background
Fat infiltration in individual muscles of sporadic inclusion body myositis (sIBM) patients has rarely been assessed.
Methods
Sixteen sIBM patients were assessed using MRI of the thighs and ...lower legs (LL). The severity of fat infiltration, proximal‐to‐distal and side asymmetries, and the correlations with clinical and functional parameters were investigated.
Results
All the patients had fat‐infiltrated muscles, and thighs were more severely affected than LL. A proximal‐to‐distal gradient of fat infiltration was mainly observed for adductors, quadriceps, sartorius, and medial gastrocnemius muscles. A strong negative correlation was observed between the whole muscle fat fraction in the thighs and LL and the Inclusion Body Myositis Functional Rating Scale and Medical Research Council scores for the lower limbs.
Conclusions
Fat infiltration in individual muscles of sIBM patients is heterogeneous in terms of proximal‐to‐distal gradient and severity was correlated with clinical scores. These results should be considered for both natural history investigation and clinical trials.
In this preliminary study, our objective was to investigate the potential of high‐resolution anatomical imaging, diffusion tensor imaging (DTI) and conventional/inhomogeneous magnetization transfer ...imaging magnetization transfer (MT)/inhomogeneous magnetization transfer (ihMT) at 3 T, analyzed with template‐extracted regions of interest, to measure the atrophy and structural changes of white (WM) and gray (GM) matter spinal cord (SC) occurring in patients with amyotrophic lateral sclerosis (ALS). Ten patients with ALS and 20 age‐matched healthy controls were recruited. SC GM and WM areas were automatically segmented using dedicated templates. Atrophy indices were evaluated from T2*‐weighted images at each vertebral level from cervical C1 to C6. DTI and ihMT metrics were quantified within the corticospinal tract (CST), posterior sensory tract (PST) and anterior GM (aGM) horns at the C2 and C5 levels. Clinical disabilities of patients with ALS were evaluated using the Revised ALS Functional Rating Scale, upper motor neuron (UMN) and Medical Research Council scorings, and correlated with MR metrics. Compared with healthy controls, GM and WM atrophy was observed in patients with ALS, especially at lower cervical levels, where a strong correlation was also observed between GM atrophy and the UMN score (R = −0.75, p = 0.05 at C6). Interestingly, a significant decrease in ihMT ratio was found in all regions of interest (p < 0.0008), fractional anisotropy (FA) and MT ratios decreased significantly in CST, especially at C5 (p < 0.005), and λ// (axial diffusivity) decreased significantly in CST (p = 0.0004) and PST (p = 0.003) at C2. Strong correlations between MRI metrics and clinical scores were also found (0.47 < |R| < 0.87, p < 0.05). Altogether, these preliminary results suggest that high‐resolution anatomical imaging and ihMT imaging, in addition to DTI, are valuable for the characterization of SC tissue impairment in ALS. In this study, in addition to an important SC WM demyelination, we also observed, for the first time in ALS, impairments of cervical aGM.
A high‐resolution, multi‐parametric magnetic resonance (MR) protocol, including diffusion tensor imaging and inhomogeneous magnetization transfer imaging, was combined with an atlas‐based analysis using dedicated spinal cord templates to evaluate region‐specific impairments of the cervical spinal cord in amyotrophic lateral sclerosis (ALS). The preliminary results suggested that this high‐resolution, multi‐parametric MR protocol is valuable for the characterization of spinal cord tissue impairment in ALS. More particularly, evidence for important white matter demyelination and impairment of cervical anterior gray matter, reported for the first time in ALS, was observed.
Background
Conduction blocks (CB) are the diagnostic hallmark of multifocal motor neuropathy (MMN). Conventional nerve conduction studies cannot detect CB above Erb's point. Our purpose was to ...compare the performance of the motor evoked potential with triple stimulation technique (MEP‐TST) and MRI in the detection of abnormalities of the brachial plexus.
Methods
Examinations were performed on 26 patients with MMN (11 definite, 6 probable, 9 possible), of whom 7 had no CB.
Results
MEP‐TST detected proximal CB in 19/26 patients. Plexus MRI showed T2 hyperintensity in 18/26 patients, with nerve enlargement in 14/18. A combination of both techniques increased the detection rate of brachial plexus abnormalities to 96% of patients (25/26).
Conclusions
MEP‐TST and MRI have high sensitivities for detecting brachial plexus abnormalities. A combination of the two techniques increases the detection rate of supportive criteria for the diagnosis of MMN.
Background and purpose
Biallelic variants in SORD have been reported as one of the main recessive causes for hereditary peripheral neuropathies such as Charcot–Marie–Tooth disease type 2 (CMT2) and ...distal hereditary motor neuropathy (dHMN) resulting in lower limb (LL) weakness and muscular atrophy. In this study, phenotype and genotype landscapes of SORD‐related peripheral neuropathies were described in a French and Swiss cohort. Serum sorbitol dosages were used to classify SORD variants.
Methods
Patients followed at neuromuscular reference centres in France and Switzerland were ascertained. Sanger sequencing and next generation sequencing were performed to sequence SORD, and mass spectrometry was used to measure patients' serum sorbitol.
Results
Thirty patients had SORD peripheral neuropathy associating LL weakness with muscular atrophy, foot deformities (87%), and sometimes proximal LL weakness (20%) or distal upper limb weakness (50%). Eighteen had dHMN, nine had CMT2, and three had intermediate CMT. Most of them had a mild or moderate disease severity. Sixteen carried a homozygous c.757delG (p.Ala253Glnfs*27) variant, and 11 carried compound heterozygous variants, among which four variants were not yet reported: c.403C > G, c.379G > A, c.68_100 + 1dup, and c.850dup. Two unrelated patients with different origins carried a homozygous c.458C > A variant, and one patient carried a new homozygous c.786 + 5G > A variant. Mean serum sorbitol levels were 17.01 mg/L ± 8.9 SD for patients carrying SORD variants.
Conclusions
This SORD‐inherited peripheral neuropathy cohort of 30 patients showed homogeneous clinical presentation and systematically elevated sorbitol levels (22‐fold) compared to controls, with both diagnostic and potential therapeutic implications.
ABSTRACT
Introduction
We propose a motor unit number index (MUNIX) global sum score in amyotrophic lateral sclerosis (ALS) to estimate the loss of functional motor units.
Methods
MUNIX was assessed ...for 18 ALS patients and 17 healthy controls in 7 muscles: the abductor pollicis brevis (APB), abductor digiti minimi (ADM), tibialis anterior (TA), deltoid, trapezius, submental complex, and orbicularis oris.
Results
MUNIX was significantly lower in ALS patients than in healthy controls for the APB, ADM, TA, and trapezius muscles. The MUNIX sum score of 4 muscles (ADM + APB + trapezius + TA) was lower in ALS patients (P = 0.01) and was correlated with clinical scores.
Discussion
The global MUNIX sum score proposed in this study estimates the loss of lower motor neurons in several body regions, including the trapezius, and is correlated with clinical impairment in ALS patients. Muscle Nerve 56: 202–206, 2017
ABSTRACT
Introduction: There is uncertainty as to whether the Guillain‐Barré syndrome (GBS) subtypes, acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy ...(AMAN), can be diagnosed electrophysiologically. Methods: We prospectively included 58 GBS patients. Electrodiagnostic testing (EDX) was performed at means of 5 and 33 days after disease onset. Two traditional and one recent criteria sets were used to classify studies as demyelinating or axonal. Results were correlated with anti‐ganglioside antibodies and reversible conduction failure (RCF). Results: No classification shifts were observed, but more patients were classified as axonal with recent criteria. RCF and anti‐ganglioside antibodies were present in both subtypes, more frequently in the axonal subtype. Discussion: Serial EDX has no effect on GBS subtype proportions. The absence of exclusive correlation with RCF and anti‐ganglioside antibodies may challenge the concept of demyelinating and axonal GBS subtypes based upon electrophysiological criteria. Frequent RCF indicates that nodal/paranodal alterations may represent the main pathophysiology. Muscle Nerve 58: 23–28, 2018.
•Motor unit number index can provide information on the prognosis of the disease at the first visit in ALS patients.•Motor unit number index score declines faster than the ALS functional rating scale ...and vital capacity.•A motor unit number index score greater than 378 at the patient’s first visit predicts survival beyond one year with a sensitivity of 82% and a specificity of 56%.
To evaluate the associations between motor unit number index (MUNIX) and disease progression and prognosis in amyotrophic lateral sclerosis (ALS) in a large-scale longitudinal study.
MUNIX was performed at the patient's first visit, at 3, 6, and 12 months in 4 muscles. MUNIX data from the patients were compared with those from 38 age-matched healthy controls. Clinical data included the revised ALS functional rating scale (ALSFRS-R), the forced vital capacity (FVC), and the survival of the patients.
Eighty-two patients were included at baseline, 62 were evaluated at three months, 48 at six months, and 33 at twelve months. MUNIX score was lower in ALS patients compared to controls. At baseline, MUNIX was correlated with ALSFRS-R and FVC. Motor unit size index (MUSIX) was correlated with patient survival. Longitudinal analyses showed that MUNIX decline was greater than ALSFRS-R decline at each evaluation. A baseline MUNIX score greater than 378 predicted survival over the 12-month period with a sensitivity of 82% and a specificity of 56%.
This longitudinal study suggests that MUNIX could be an early quantitative marker of disease progression and prognosis in ALS.
MUNIX might be considered as potential indicator for monitoring disease progression.
Introduction
In peripheral neuropathies with antibodies against Myelin Associated Glycoprotein (MAG), an IgM monoclonal gammopathy recognizes a specific epitope called Human Natural Killer 1 (HNK1) ...shared by NK lymphocytes and several components of the peripheral nerve myelin. Recently an ELISA test has been developed to detect antibodies against HNK1 epitope. Objectives were to determine the usefulness of this assay in the management of anti-MAG neuropathy.
Methods
Anti-HNK1 antibodies were assessed with the GanglioCombi™ MAG ELISA test (Buhlmann) in 41 anti-MAG neuropathies and in 118 controls: 34 chronic inflammatory demyelinating polyradiculoneuropathies, 3 Miller Fisher syndromes, 12 sensory neuronopathies, 63 length-dependent axonal sensory polyneuropathies, 6 healthy controls. Anti-HNK1 antibody was tested before and 1 year after rituximab therapy in seven patients with anti-MAG neuropathy.
Results
Anti-HNK1 antibodies were positive in 40/41 anti-MAG neuropathies, and in 1/118 controls (sensitivity 98%, specificity 99%). Only considering controls with IgM paraprotein, specificity was 96% (23/24). In anti-MAG neuropathies, anti-HNK1 titre was correlated with sensory deficiency evaluated with the INCAT sensory sum score (
r
= 0.4,
p
= 0.01) and with disability evaluated with the Rasch-built Overall Disability Scale (
r
=
-
0.4,
p
= 0.01) and Overall Neuropathy Limitation Scale (
r
= 0.4,
p
= 0.02). Anti-HNK1 titres were not related to age, disease duration, atypical clinical features and anti-MAG antibodies titres. Anti-MAG titres were not associated with disease severity. Anti-HNK1 titres were decreased by 18% 1 year after rituximab treatment.
Conclusions
Anti-HNK1 antibodies have good sensitivity and specificity for the diagnosis of anti-MAG neuropathy. Interestingly, anti-HNK1 titres are related to the disease severity and decrease after rituximab infusions.
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