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Recent studies suggest that Th2 cells play a key role in the pathology of secondary lymphedema by elaborating cytokines such as IL4 and IL13. The aim of this study was to test the efficacy of QBX258, a monoclonal IL4/IL13 neutralizing antibody, in women with breast cancer–related lymphedema (BCRL). We enrolled nine women with unilateral stage I/II BCRL and treated them once monthly with intravenous infusions of QBX258 for 4 months. We measured limb volumes, bioimpedance, and skin tonometry, and analyzed the quality of life (QOL) using a validated lymphedema questionnaire (Upper Limb Lymphedema 27, ULL-27) before treatment, immediately after treatment, and 4 months following treatment withdrawal. We also obtained 5 mm skin biopsies from the normal and lymphedematous limbs before and after treatment. Treatment was well-tolerated; however, one patient with a history of cellulitis developed cellulitis during the trial and was excluded from further analysis. We found no differences in limb volumes or bioimpedance measurements after drug treatment. However, QBX258 treatment improved skin stiffness (p < 0.001) and improved QOL measurements (Physical p < 0.05, Social p = 0.01). These improvements returned to baseline after treatment withdrawal. Histologically, treatment decreased epidermal thickness, the number of proliferating keratinocytes, type III collagen deposition, infiltration of mast cells, and the expression of Th2-inducing cytokines in the lymphedematous skin. Our limited study suggests that immunotherapy against Th2 cytokines may improve skin changes and QOL of women with BCRL. This treatment appears to be less effective for decreasing limb volumes; however, additional studies are needed.

To date, little is known about the usefulness of ultra-high frequency ultrasound (UHF-US, 50–70 MHz) in clinical practice for the diagnosis of dysimmune neuropathies. We present a prospective study aimed at comparing UHF-US alterations of nerves and fascicles in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), distal CIDP (d-CIDP) and anti-MAG neuropathy and their relationships with clinical and electrodiagnostic (EDX) features. 28 patients were included (twelve CIDP, 6 d-CIDP and 10 anti-MAG) and ten healthy controls. Each patient underwent neurological examination, EDX and UHF-US study of median and ulnar nerves bilaterally. UHF-US was reliable in differentiating immune neuropathies from controls when using mean and/or segmental nerve and/or fascicle cross-sectional area (CSA); furthermore, fascicle ratio (fascicle/nerve CSA) was a reliable factor for differentiating d-CIDP from other types of polyneuropathies. The fascicle CSA appears to be more increased in CIDP and its variant than in anti-MAG neuropathy. UHF-US offers information beyond simple nerve CSA and allows for a better characterization of the different forms of dysimmune neuropathies.

Introduction/aims Chronic inflammatory demyelinating polyneuropathy (CIDP) and its variants are characterized by nerve enlargement (NE), particularly in the proximal segments of the median nerve (MN) and cervical roots, as assessed by ultrasound (US). NE is typically moderate and seldom exceeds double the normal size of the cross‐sectional area (CSA). Furthermore, limited knowledge exists regarding the changes in the internal structure of nerves evaluated with high‐frequency ultrasound. This study describes three cases of significant CIDP‐NE assessed with an ultra‐high‐frequency probe (UHF‐US; 33 MHz) showing how changes in US‐nerve images may guide treatment choice. Methods Three patients diagnosed with multifocal CIDP and followed for several years in our department were studied. Clinical evaluations, electrodiagnostic studies (EDX), laboratory analyses, and UHF‐US of the nerves were performed. Results Nerve conduction studies (NCS) revealed severe demyelinating neuropathy with conduction blocks, reduced motor conduction velocities (MCV) in all cases, and secondary axonal degeneration in two cases. Ultrasound showed NE in the roots and nerves, with altered echogenicity and modification of internal nerve structure. A second‐line treatment was successfully started in three patients. Discussion UHF‐US allows for the evaluation of structural changes in the nerve. NE and alterations in internal structure can be considered ultrasound markers of disease severity, guiding therapeutic decisions. This study highlights the potential of ultra‐high frequency ultrasound (28–33 MHz) to detect internal structural changes in enlarged nerves in multifocal CIDP. In three patients, altered echogenicity and fascicular architecture were associated with severe electrophysiological findings and guided treatment escalation. These findings support the role of UHF‐US as a tool to monitor disease severity and tailor therapy.

Thymoma is a tumor originating from thymic gland, frequently manifesting with paraneoplastic neurological disorders. Its association with paraneoplastic dysautonomia is relatively uncommon. Here, we describe the challenging case of a 71 year-old female who developed subacute autonomic failure with digestive pseudo-obstruction, dysphagia, urinary tract dysfunction and orthostatic hypotension complicating an underlying extrapyramidal syndrome that had started 3 months before hospital admission. Autonomic symptoms had 2-month course and acutely worsened just before and during hospitalization. Combination of severe dysautonomia and parkinsonism mimicked rapidly progressing multiple system atrophy. However, diagnostic exams showed thymic tumor with positive anti-Hu antibodies on both serum and cerebrospinal fluid. Complete response of dysautonomia to immunoglobulins followed by thymectomy confirmed the diagnosis of anti-Hu-related paraneoplastic neurological syndrome. With regards to extrapyramidal symptoms, despite previous descriptions of paraneoplastic parkinsonism caused by other antineuronal antibodies, in our case no relation between anti-Hu and parkinsonism could be identified. A literature review of published reports describing anti-Hu positivity in thymic neoplasms highlighted that a definite autonomic disease due to anti-Hu antibodies is extremely rare in patients with thymoma but without myasthenia gravis, with only one case published so far.

Introduction: The purpose of this study was to evaluate the most commonly used preoperative assessment tools for patients undergoing surgical treatment for secondary upper extremity lymphedema. Methods: This was a prospective cohort study performed at a tertiary cancer center specializing in the treatment of secondary lymphedema. Lymphedema evaluation included limb volume measurements, bio-impedance, indocyanine green lymphography, lymphoscintigraphy, magnetic resonance angiography, lymphedema life impact scale (LLIS) and upper limb lymphedema 27 (ULL-27) questionnaires. Results: 118 patients were evaluated. Limb circumference underestimated lymphedema compared to limb volume. Bioimpedance (L-Dex) scores highly correlated with limb volume excess (r2 = 0.714, p < 0.001). L-Dex scores were highly sensitive and had a high positive predictive value for diagnosing lymphedema in patients with a volume excess of 10% or more. ICG was highly sensitive in identifying lymphedema. Lymphoscintigraphy had an overall low sensitivity and specificity for the diagnosis of lymphedema. MRA was highly sensitive in diagnosing lymphedema and adipose hypertrophy as well as useful in identifying axillary vein obstruction and occult metastasis. Patients with minimal limb volume difference still demonstrated significantly impaired quality of life. Conclusion: Preoperative assessment of lymphedema is complex and requires multimodal assessment. MRA, L-Dex, ICG, and PROMs are all valuable components of preoperative assessment.

Background Facioscapulohumeral dystrophy (FSHD) and Myasthenia Gravis (MG) are well‐known rare neuromuscular diseases of respectively genetic and acquired origin. Among muscular dystrophies, the co‐occurrence of MG with FSHD is the most common, representing a non‐negligible “double trouble”. Here, we aim to describe a series of patients with coexistence of these two rare disorders and combine this with a review of the literature to identify common elements which might provide useful clues when evaluating a FSHD patient with uncommon clinical presentation compatible with MG. Methods We retrospectively collected demographic, clinical, and laboratory data of patients affected by both FSHD and MG followed at the Nice University Center, and we performed a review of the literature. Results We identified 10 patients in our cohort, 7 females. All patients have a D4Z4 4qA allele of 7–10 RU, a disease onset > 45 years and a mean FSHD score of 9.6 ± 2 at the last evaluation. The mean age of onset of MG was 68.5 ± 7.6 years; all patients presented with anti‐AChR antibodies and without thymic pathology, and MG appeared in all but two patients after FSHD. We identified 9 case reports in the literature. All of them presented with AChR positivity. The majority of them presented with a late and very late onset MG and without thymic pathology. Conclusions Our results underline the need for careful clinical evaluation to identify uncommon features, especially in elderly FSHD patients carrying a D4Z4 4qA allele of 7–10 RU to exclude the coexistence of other treatable neuromuscular conditions.

Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is a progressive neuromuscular disorder with no approved treatments. Identifying reliable biomarkers is critical to monitor disease severity, activity, and progression. Interleukin-6 (IL-6) has been proposed as a candidate biomarker, but longitudinal validation is limited. We analyzed pooled data from two prospective longitudinal cohorts: CTRN-FSHD France (NCT04038138) and Cytokine FSHD (NCT04694456), each comprising 30 genetically confirmed ambulant FSHD1 patients. Serum IL-6 levels and clinical assessments were collected at baseline (M0), 12 months (M12), and 18 months (M18); whole-body muscle MRI (T1-weighted and STIR sequences) was obtained at M0 and M12. Associations between IL-6 levels and clinical severity scores, functional measures, and MRI-derived muscle composition were evaluated. Serum IL-6 levels correlated significantly with clinical severity metrics, including Clinical Severity Score, 6-Minute Walk Test, Manual Muscle Testing, and Motor Function Measure Domain 1 at all time points. Higher IL-6 levels were associated with increased muscle fat infiltration and free water content compatible with muscle edema on MRI. Longitudinal analyses showed that increases in IL-6 over 12 months were significantly correlated with changes in T1 (fat infiltration) and STIR (muscle edema) composite scores, reflecting structural and inflammatory disease progression. These findings validate IL-6 as a biomarker of FSHD1 severity and underscore its potential as an activity and progression biomarker. The correlation between IL-6, clinical scores, and MRI-based muscle composition changes highlights its potential utility for monitoring disease evolution and evaluating therapeutic responses in FSHD1 patients.

A 56-year-old immunocompetent male developed brainstem encephalitis complicating Ramsay Hunt syndrome. The disease had a slowly progressing course of months after the triggering infection, much longer than previously reported. Furthermore, magnetic resonance imaging, physical-chemical, and cell count analyses on cerebrospinal fluid were normal, whereas polymerase chain reaction for varicella zoster virus DNA was positive. The simultaneous negativity of both imaging and basic CSF exams is very rare, although possible event which confirms the irreplaceable role of viral screening on CSF. A systematic review of similar reports with highlights on the unusual aspects of our case is also presented.

NMR spectroscopy plays a major role in the determination of the structures and dynamics of proteins and other biological macromolecules. Chemical shifts are the most readily and accurately measurable NMR parameters, and they reflect with great specificity the conformations of native and nonnative states of proteins. We show, using 11 examples of proteins representative of the major structural classes and containing up to 123 residues, that it is possible to use chemical shifts as structural restraints in combination with a conventional molecular mechanics force field to determine the conformations of proteins at a resolution of 2 Å or better. This strategy should be widely applicable and, subject to further development, will enable quantitative structural analysis to be carried out to address a range of complex biological problems not accessible to current structural techniques.