Clinical utility of anti-cytosolic 5\u27-nucleotidase 1A antibody in idiopathic inflammatory myopathies

OBJECTIVE: To define the clinicopathologic features and diagnostic utility associated with anti-cytosolic 5\u27-nucleotidase 1A (NT5C1A) antibody seropositivity in idiopathic inflammatory myopathies (IIMs). METHODS: Anti-NT5C1A antibody status was clinically tested between 2014 and 2019 in the Washington University neuromuscular clinical laboratory. Using clinicopathologic information available for 593 patients, we classified them as inclusion body myositis (IBM), dermatomyositis, antisynthetase syndrome, immune-mediated necrotizing myopathy (IMNM), nonspecific myositis, or noninflammatory muscle diseases. RESULTS: Of 593 patients, anti-NT5C1A antibody was found in 159/249 (64%) IBM, 11/53 (21%) dermatomyositis, 7/27 (26%) antisynthetase syndrome, 9/76 (12%) IMNM, 20/84 (24%) nonspecific myositis, and 6/104 (6%) noninflammatory muscle diseases patients. Among patients with IBM, anti-NT5C1A antibody seropositive patients had more cytochrome oxidase-negative fibers compared with anti-NT5C1A antibody seronegative patients. Among 14 IBM patients initially negative for anti-NT5C1A antibody, three patients (21%) converted to positive. Anti-NT5C1A antibody seropositivity did not correlate with malignancy, interstitial lung disease, response to treatments in dermatomyositis, antisynthetase syndrome, and IMNM, or survival in IIMs. INTERPRETATION: Anti-NT5C1A antibody is associated with IBM. However, the seropositivity can also be seen in non-IBM IIMs and it does not correlate with any prognostic factors or survival

Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS

Intravenous Immunoglobulin Treatment in Multifocal Motor Neuropathy

# The Author(s) 2010. This article is published with open access at Springerlink.com Introduction Multifocal motor neuropathy (MMN) is characterized by asymmetric weakness of limbs and the electrophysiological finding of conduction block in motor nerves. Conduction block is the inability of nerves to propagate action potentials and is probably caused b

Intensive Teenage Activity Is Associated With Greater Muscle Hyperintensity on T1W Magnetic Resonance Imaging in Adults With Dysferlinopathy

Practice of sports during childhood or adolescence correlates with an earlier onset and more rapidly progressing phenotype in dysferlinopathies. To determine if this correlation relates to greater muscle pathology that persists into adulthood, we investigated the effect of exercise on the degree of muscle fatty replacement measured using muscle MRI. We reviewed pelvic, thigh and leg T1W MRI scans from 160 patients with genetically confirmed dysferlinopathy from the Jain Foundation International clinical outcomes study in dysferlinopathy. Two independent assessors used the Lamminen-Mercuri visual scale to score degree of fat replacement in each muscle. Exercise intensity for each individual was defined as no activity, minimal, moderate, or intensive activity by using metabolic equivalents and patient reported frequency of sports undertaken between the ages of 10 and 18. We used ANCOVA and linear modeling to compare the mean Lamminen-Mercuri score for the pelvis, thigh, and leg between exercise groups, controlling for age at assessment and symptom duration. Intensive exercisers showed greater fatty replacement in the muscles of the pelvis than moderate exercisers, but no significant differences of the thigh or leg. Within the pelvis, Psoas was the muscle most strongly associated with this exercise effect. In patients with a short symptom duration of <15 years there was a trend toward greater fatty replacement in the muscles of the thigh. These findings define key muscles involved in the exercise-phenotype effect that has previously been observed only clinically in dysferlinopathy and support recommendations that pre-symptomatic patients should avoid very intensive exercise

Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study

Background Late-onset Pompe disease is characterized by progressive skeletal myopathy followed by respiratory muscle weakness, typically leading to loss of ambulation and respiratory failure. In this population, enzyme replacement therapy (ERT) with alglucosidase alfa has been shown to stabilize respiratory function and improve mobility and muscle strength. Muscle pathology and glycogen clearance from skeletal muscle in treatment-naïve adults after ERT have not been extensively examined. Methods This exploratory, open-label, multicenter study evaluated glycogen clearance in muscle tissue samples collected pre- and post- alglucosidase alfa treatment in treatment-naïve adults with late-onset Pompe disease. The primary endpoint was the quantitative reduction in percent tissue area occupied by glycogen in muscle biopsies from baseline to 6 months. Secondary endpoints included qualitative histologic assessment of tissue glycogen distribution, secondary pathology changes, assessment of magnetic resonance images (MRIs) for intact muscle and fatty replacement, and functional assessments. Results Sixteen patients completed the study. After 6 months of ERT, the percent tissue area occupied by glycogen in quadriceps and deltoid muscles decreased in 10 and 8 patients, respectively. No changes were detected on MRI from baseline to 6 months. A majority of patients showed improvements on functional assessments after 6 months of treatment. All treatment-related adverse events were mild or moderate. Conclusions This exploratory study provides novel insights into the histopathologic effects of ERT in late-onset Pompe disease patients. Ultrastructural examination of muscle biopsies demonstrated reduced lysosomal glycogen after ERT. Findings are consistent with stabilization of disease by ERT in treatment-naïve patients with late-onset Pompe disease

Task-related enhancement in corticomotor excitability during haptic sensing with the contra- or ipsilateral hand in young and senior adults

<p>Abstract</p> <p>Background</p> <p>Haptic sensing with the fingers represents a unique class of manipulative actions, engaging motor, somatosensory and associative areas of the cortex while requiring only minimal forces and relatively simple movement patterns. Using transcranial magnetic stimulation (TMS), we investigated task-related changes in motor evoked potential (MEP) amplitude associated with unimanual haptic sensing in two related experiments. In Experiment I, we contrasted changes in the excitability of the hemisphere controlling the task hand in young and old adults under two trial conditions, i.e. when participants either touched a fine grating (<it>smooth trials</it>) or touched a coarse grating to detect its groove orientation (<it>grating trials</it>). In Experiment II, the same contrast between tasks was performed but with TMS applied over the hemisphere controlling the resting hand, while also addressing hemispheric (right vs. left) and age differences.</p> <p>Results</p> <p>In Experiment I, a main effect of <it>trial type </it>on MEP amplitude was detected (p = 0.001), MEPs in the task hand being ~50% larger during grating than smooth trials. No interaction with age was detected. Similar results were found for Experiment II, <it>trial type </it>having a large effect on MEP amplitude in the resting hand (p < 0.001) owing to selective increase in MEP size (~2.6 times greater) for grating trials. No interactions with age or side (right vs. left) were detected.</p> <p>Conclusions</p> <p>Collectively, these results indicate that adding a haptic component to a simple unilateral finger action can elicit robust corticomotor facilitation not only in the working hemisphere but also in the opposite hemisphere. The fact that this facilitation seems well preserved with age, when task difficulty is adjusted, has some potential clinical implications.</p

Differential modulation of corticospinal excitability during haptic sensing of 2-D patterns vs. textures

<p>Abstract</p> <p>Background</p> <p>Recently, we showed a selective enhancement in corticospinal excitability when participants actively discriminated raised 2-D symbols with the index finger. This extra-facilitation likely reflected activation in the premotor and dorsal prefrontal cortices modulating motor cortical activity during attention to haptic sensing. However, this parieto-frontal network appears to be finely modulated depending upon whether haptic sensing is directed towards material or geometric properties. To examine this issue, we contrasted changes in corticospinal excitability when young adults (n = 18) were engaged in either a roughness discrimination on two gratings with different spatial periods, or a 2-D pattern discrimination of the relative offset in the alignment of a row of small circles in the upward or downward direction.</p> <p>Results</p> <p>A significant effect of task conditions was detected on motor evoked potential amplitudes, reflecting the observation that corticospinal facilitation was, on average, ~18% greater in the pattern discrimination than in the roughness discrimination.</p> <p>Conclusions</p> <p>This differential modulation of corticospinal excitability during haptic sensing of 2-D patterns vs. roughness is consistent with the existence of preferred activation of a visuo-haptic cortical dorsal stream network including frontal motor areas during spatial vs. intensive processing of surface properties in the haptic system.</p