Longitudinal Muscle Biopsies Reveal Inter- and Intra-Subject Variability in Cancer Cachexia: Paving the Way for Biopsy-Guided Tailored Treatment.

In the rapidly evolving landscape of cancer cachexia research, the development and refinement of diagnostic and predictive biomarkers constitute an ongoing challenge. This study aims to introduce longitudinal muscle biopsies as a potential framework for disease monitoring and treatment. The initial feasibility and safety assessment was performed for healthy mice and rats that received two consecutive muscle biopsies. The assessment was performed by utilizing three different tools. Subsequently, the protocol was also applied in leiomyosarcoma tumor-bearing rats. Longitudinal muscle biopsies proved to be a safe and feasible technique, especially in rat models. The application of this protocol to tumor-bearing rats further affirmed its tolerability and feasibility, while microscopic evaluation of the biopsies demonstrated varying levels of muscle atrophy with or without leukocyte infiltration. In this tumor model, sequential muscle biopsies confirmed the variability of the cancer cachexia evolution among subjects and at different time-points. Despite the abundance of promising cancer cachexia data during the past decade, the full potential of muscle biopsies is not being leveraged. Sequential muscle biopsies throughout the disease course represent a feasible and safe tool that can be utilized to guide precision treatment and monitor the response in cancer cachexia research.

Treatment of acquired transthyretin amyloidosis in domino liver transplantation.

BACKGROUND: Domino liver transplantation (DLT) has been commonly used during the last two decades to partly meet the high need for liver transplants. However, the recipients of grafts from patients with noncirrhotic inherited metabolic disorders may ultimately develop metabolic syndrome, and management is usually intricate, being complicated by the underlying initial disorder, other comorbidities, and post-transplantation conditions. CASE: We report here the management and the outcome in a patient with acquired transthyretin amyloidosis after DLT and significant comorbidities. Final treatment with a transthyretin gene silencing agent, patisiran, was well tolerated and resulted in remission of the aggravating neurological deficits in a follow-up period of 2 years. CONCLUSIONS: The case presented here supports the concept that patisiran can target the hepatocytes producing the mutated transthyretin in acquired transthyretin amyloidosis, as efficiently as in hereditary transthyretin amyloidosis (hATTR), and can be used to treat patients with transthyretin amyloidosis after DLT.

A Greek National Cross-Sectional Study on Myotonic Dystrophies.

Myotonic Dystrophies (DM, Dystrophia Myotonia) are autosomal dominant inherited myopathies with a high prevalence across different ethnic regions. Despite some differences, mainly due to the pattern of muscle involvement and the age of onset, both forms, DM1 and DM2, share many clinical and genetic similarities. In this study, we retrospectively analyzed the medical record files of 561 Greek patients, 434 with DM1 and 127 with DM2 diagnosed in two large academic centers between 1994-2020. The mean age at onset of symptoms was 26.2 ± 15.3 years in DM1 versus 44.4 ± 17.0 years in DM2 patients, while the delay of diagnosis was 10 and 7 years for DM1 and DM2 patients, respectively. Muscle weakness was the first symptom in both types, while myotonia was more frequent in DM1 patients. Multisystemic involvement was detected in the great majority of patients, with cataracts being one of the most common extramuscular manifestations, even in the early stages of disease expression. In conclusion, the present work, despite some limitations arising from the retrospective collection of data, is the first record of a large number of Greek patients with myotonic dystrophy and emphasizes the need for specialized neuromuscular centers that can provide genetic counseling and a multidisciplinary approach.

Clinical features and diagnostic tools in idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIMs) are rare autoimmune disorders affecting primarily muscles, but other organs can be involved. This review describes the clinical features, diagnosis and treatment for IIMs, namely polymyositis (PM), dermatomyositis (DM), sporadic inclusion body myositis (sIBM), immune-mediated necrotizing myopathy (IMNM), and myositis associated with antisynthetase syndrome (ASS). The diagnostic approach has been updated recently based on the discovery of circulating autoantibodies, which has enhanced the management of patients. Currently, validated classification criteria for IIMs allow clinical studies with well-defined sets of patients but diagnostic criteria to guide the care of individual patients in routine clinical practice are still missing. This review analyzes the clinical manifestations and laboratory findings of IIMs, discusses the efficiency of modern and standard methods employed in their workup, and delineates optimal practice for clinical care. Α multidisciplinary diagnostic approach that combines clinical, neurologic and rheumatologic examination, evaluation of electrophysiologic and morphologic muscle characteristics, and assessment of autoantibody immunoassays has been determined to be the preferred approach for effective management of patients with suspected IIMs.

A Novel Mutation of the Membrane Metallo-Endopeptidase Gene Related to Late-Onset Hereditary Polyneuropathy: Case Report and Review of the Literature.

The advent of next generation sequencing has revolutionized diagnostic approaches to hereditary polyneuropathies. Recently, mutations on the membrane metallo-endopeptidase (MME) gene, encoding neprilysin, have been related to the development of late-onset Charcot-Marie-Tooth disease type 2 (CMT2). Here, we report the first Greek patient presenting with a slowly progressive late-onset axonal polyneuropathy and a novel, likely pathogenic, heterozygous variant in the MME gene. In addition, we have performed a systematic review of all published case reports of patients with MME mutations. The results of the studies show that MME variants can be inherited as both fully penetrant autosomal-recessive and incompletely penetrant autosomal-dominant traits. A number of heterozygous variants characterized as incompletely penetrant impose an increased risk of developing a CMT2-like phenotype late in life, identical to the case study described here. Greater mutation numbers in different populations and mutation-specific functional studies will be essential to identify the pathogenicity and inheritance of more MME variants.

Trichinosis Imitating an Inflammatory Systematic Disease.

Trichinellosis (trichinosis) is a parasitic infection caused by nematodes of the genus Trichinella. Pigs are the most common source of human infection. We describe a case of a 47-year-old woman presented with a wide range of intermittent symptoms including prolonged fever, dry cough, diarrhea, rash, myalgias and arthralgias. The patient was attended by physicians with various medical specialties such as dermatologists, rheumatologists and allergiologists, but they did not establish a certain diagnosis because of the gradual onset of symptoms, raising the suspicion of a systematic disease. After extensive work up, the diagnosis of trichinosis was established with femoral muscle biopsy compatible with inflammatory myopathy of parasitic etiology with trichinosis to be the predominant diagnosis. Despite the significant delay of diagnosis for almost three months, patient was treated successfully with no further complications. Trichinellosis is a food-borne treatable infection. Preventive measures include community education especially in zones where parasite prevalence is increased, improvement of farming and cooking techniques.

Variant transthyretin amyloidosis (ATTRv) polyneuropathy in Greece: a broad overview with a focus on non-endemic unexplored regions of the country.

Comprehensive data on variant transthyretin amyloidosis polyneuropathy (ATTRv-PN) in Greece are lacking. We presently provide an overview of ATTRv-PN in Greece, focusing on unexplored non-endemic regions of the country. In total, we identified 57 cases of ATTRv-PN diagnosed over the past 25 years, including 30 from the island of Crete, an apparent endemic region. Patients carried 10 different TTR mutations (C10R; P24S; V30M; R34G; R34T; I68L; A81T; E89Q; E89K and V94A). Carriers of the common V30M mutation constituted 54.3 % of the cohort. A known founder effect for the V30M mutation was present on the island of Crete. Non-endemic cases identified outside the island of Crete are presently reported in more detail. The age of onset ranged from 25 to 77 years, with a mean of 51.1 years. A mean diagnostic delay of 3.2 years was observed. V30M patients had earlier onset and less cardiac involvement than patients carrying other mutations. Genotype-phenotype correlations were largely consistent with published data. We conclude that, with the exception of the Cretan cluster, ATTRv-PN is not endemic in the Greek population. This makes timely diagnosis more challenging, yet absolutely essential given the availability of therapies that can alter the long-term course of the disease.

Automatic Electrodiagnosis of Carpal Tunnel Syndrome Using Machine Learning.

Recent literature has revealed a long discussion about the importance and necessity of nerve conduction studies in carpal tunnel syndrome management. The purpose of this study was to investigate the possibility of automatic detection, based on electrodiagnostic features, for the median nerve mononeuropathy and decision making about carpal tunnel syndrome. The study included 38 volunteers, examined prospectively. The purpose was to investigate the possibility of automatically detecting the median nerve mononeuropathy based on common electrodiagnostic criteria, used in everyday clinical practice, as well as new features selected based on physiology and mathematics. Machine learning techniques were used to combine the examined characteristics for a stable and accurate diagnosis. Automatic electrodiagnosis reached an accuracy of 95% compared to the standard neurophysiological diagnosis of the physicians with nerve conduction studies and 89% compared to the clinical diagnosis. The results show that the automatic detection of carpal tunnel syndrome is possible and can be employed in decision making, excluding human error. It is also shown that the novel features investigated can be used for the detection of the syndrome, complementary to the commonly used ones, increasing the accuracy of the method.

Sjögren Syndrome Associated with Inflammatory Muscle Diseases.

OBJECTIVES: Sjögren's syndrome (SS) is a chronic autoimmune inflammatory disorder characterized by diminished lacrimal and salivary gland function that may affect multiple organ systems. The association of SS with inflammatory myopathies (IM), a group of diseases characterized by chronic inflammation of striated muscle and skin has been infrequently described. METHODS: We present two cases diagnosed with SS who developed IM. We have also conducted a review of the English literature to depict all available clinical evidence on the clinical association of SS with IM. RESULTS: Two female patients diagnosed with SS developed polymyositis (PM) and inclusion body myositis (IBM) respectively. The literature review identified 24 cases with coexistence of the two autoimmune conditions (SS and IM). Twenty-two patients were females and two males. Eight patients were diagnosed with IBM, 15 were diagnosed with PM and 1 with dermatomyositis. All patients had biopsy proven IM. CONCLUSIONS: There is evidence of clinical association of primary SS and IM especially with IBM and PM. Patients with SS and symptoms of muscle weakness should be investigated for associated IM.

Thrombosis and recanalization of straight sinus.

We describe a case of a 14-year-old boy who presented to the emergency department with nausea, vomiting, headache, and mental status changes. Noncontrast computed tomography scan of the brain in the emergency department revealed bilateral thalamic and striatocapsular infarcts. The patient was diagnosed with possible thrombosis of the thalamostriate veins, which was confirmed with urgent magnetic resonance venography (MRV). Magnetic resonance venography revealed that the thrombosis was extended to the straight sinus and the internal cerebral veins. Thrombosis of the straight sinus in children results in a rare stroke with inconsistent clinical manifestations, depending on collateral venous circulation of the thrombosed sinus. The diagnosis is quite difficult, especially when symptoms are nonspecific and variable. Timely diagnosis, based on the decision of performing emergency magnetic resonance imaging and MRV, followed by the administration of anticoagulation therapy may reverse this condition as in our patient who made an excellent recovery.

Patient compliance with SSRIs and gabapentin in painful diabetic neuropathy.

BACKGROUND: Anticonvulsants are widely used for treatment of painful diabetic neuropathy. Selective serotonin reuptake inhibitors (SSRIs) are not first-line drugs but are commonly prescribed medicines for chronic pain. The majority of patients are hesitant to use these drug groups, thus their compliance remains an issue. OBJECTIVE: To compare patient compliance and the effectiveness of 2 SSRIs (paroxetine or citalopram) and 1 anticonvulsant (gabapentin) in patients with painful diabetic neuropathy. METHODS: This was a 6 months prospective trial in 101 patients with painful diabetic neuropathy and minimum score of 2 on a pain intensity scale ranging of 0 to 4. Compliance was assessed with patient interviews and pill counts. Adverse events, early discontinuation or satisfaction with treatment were also evaluated. RESULTS: Patients receiving SSRIs reported greater satisfaction and fewer concerns of the side-effects with their treatment (P<0.05) compared with the patients taking gabapentin. There was statistically significant better mood in the SSRI group (P<0.05). Overall, 43.5% of those taking SSRIs noticed no effect on the pain control, 50% felt better, and 6.5% felt worse. Among the patients taking gabapentin, 51% felt better, 40.5% noticed no effect, and 8.5% felt worse. Finally, on the pill count, more patients on SSRIs (93.5%) than on gabapentin (82.9%) were taking over the 75% of their medication (P<0.05). CONCLUSIONS: The lack of negative effects on quality of life, the better compliance, and the comparable efficiency of SSRIs suggest that these drugs may be considered as alternative to gabapentin in painful diabetic neuropathy.

A two-stage method for MUAP classification based on EMG decomposition.

A method for the extraction and classification of individual motor unit action potentials (MUAPs) from needle electromyographic signals is presented. The proposed method automatically decomposes MUAPs and classifies them into normal, neuropathic or myopathic using a two-stage feature-based classifier. The method consists of four steps: (i) preprocessing of EMG recordings, (ii) MUAP clustering and detection of superimposed MUAPs, (iii) feature extraction and (iv) MUAP classification using a two-stage classifier. The proposed method employs Radial Basis Function Artificial Neural Networks and decision trees. It requires minimal use of tuned parameters and is able to provide interpretation for the classification decisions. The approach has been validated on real EMG recordings and an annotated collection of MUAPs. The success rate for MUAP clustering is 96%, while the accuracy for MUAP classification is about 89%.

Lumbar nerve root avulsions with secondary ipsilateral hip dysplasia in a child.

We report on an 8-year-old child with avulsions of the left L3, L4 and L5 nerve roots and traumatic meningoceles that were not associated with lumbar spine or pelvic girdle fractures. The patient had a history of a road traffic accident. Plain radiographs of the pelvis revealed left hip dysplasia. The magnetic resonance imaging findings of the lumbar spine are illustrated. The pathogenesis of lumbar nerve root avulsions and their association with ipsilateral hip dysplasia are discussed.