Inclusion body myositis-health-related quality of life and care situation during phases of the "patience journey" in Germany: results from a qualitative study.

BACKGROUND: To understand the health-related quality of life (HRQoL) in inclusion body myositis (IBM) from a holistic perspective on the background of a complex care situation. The focus was on how the patient journey may be structured over the course of this rare disease. METHODS: An exploratory qualitative study was performed via in-depth semi-structured interviews. Seven patients (males n = 5) with 2011 European Neuromuscular Centre (ENMC) IBM criteria from the German IBM patient registry were interviewed for this study. The dynamic network approach of resilience and the throughput-model of health services research were used to structure the qualitative analysis. RESULTS: Our results suggest that IBM patients experience the holistic HRQoL and care situation typically in four phases: (1) uncertainty about physical vulnerability until diagnosis, (2) promising treatment approaches, (3) self-management and dyadic coping, (4) weak body, busy mind and caregiver burden. The homophonous in-vivo code "patience journey" describes the frequently reported emotional perspective of the patient journey. Although the overarching theme of perceived social support varied throughout these phases, a reliable patient-partner-dyad may lead to improved HRQoL in the long-term. CONCLUSIONS: New hypotheses for future quantitative research were generated to better understand the IBM patients' burden in the long term. The identified relevance of social support emphasizes the patients' need to handle IBM as manageable in medical settings. During exhausting phases of IBM progression, more effective care elements for patients and their partners could disclose varying needs. Strengthening multi-professional healthcare services via individualised informational, practical, or emotional support could improve HRQoL, especially since there is no curative treatment available so far.

Long-term follow-up in patients with CCFDN syndrome.

OBJECTIVE: We describe the 10-year follow-up in a cohort of 16 patients with genetically confirmed congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) syndrome, providing new insights in the clinical course of the disease. METHODS: We performed a detailed clinical and paraclinical characterization and 10-year follow-up study in 16 patients with molecularly defined CCFDN syndrome, illustrating that CCFDN is a severe disabling disorder. RESULTS: All patients initially presented with congenital cataracts along with strabismus, facial dysmorphism, short stature, and demyelinating neuropathy. In all patients, paresis of small hand muscles and foot extensors worsened with disease progression, while ataxia scores remained stable or improved. Nerve conduction velocity was normal in early infancy up to 18 months, decreased to approximately 20 m/s around age 10 years, and then remained stable; distal motor latency was prolonged. Sensory nerve conduction velocities were slowed, and initially of normal amplitude. With disease progression, both sensory and motor nerves showed reduction of amplitudes indicating axonal loss. In 6 patients, acute severe proximal weakness and myalgia after febrile infections, along with rhabdomyolysis, myoglobinuria, and hyperCKemia, led to a less favorable outcome and permanent loss of ambulation in 3 patients. CONCLUSIONS: CCFDN should be classified as a recessive demyelinating sensory-motor neuropathy, and axonal loss is a major determinant of long-term outcomes and disability. Patients benefit from early and ongoing physiotherapy, and should be thoroughly counseled regarding virus-triggered rhabdomyolysis and the risk of malignant hyperthermia. Whether supplementation with liposoluble vitamins results in a therapeutic benefit should be evaluated in further studies.

Evaluation of the therapeutic potential of carbonic anhydrase inhibitors in two animal models of dystrophin deficient muscular dystrophy.

Duchenne Muscular Dystrophy is an inherited muscle degeneration disease for which there is still no efficient treatment. However, compounds active on the disease may already exist among approved drugs but are difficult to identify in the absence of cellular models. We used the Caenorhabditis elegans animal model to screen a collection of 1000 already approved compounds. Two of the most active hits obtained were methazolamide and dichlorphenamide, carbonic anhydrase inhibitors widely used in human therapy. In C. elegans, these drugs were shown to interact with CAH-4, a putative carbonic anhydrase. The therapeutic efficacy of these compounds was further validated in long-term experiments on mdx mice, the mouse model of Duchenne Muscular Dystrophy. Mice were treated for 120 days with food containing methazolamide or dichlorphenamide at two doses each. Musculus tibialis anterior and diaphragm muscles were histologically analyzed and isometric muscle force was measured in M. extensor digitorum longus. Both substances increased the tetanic muscle force in the treated M. extensor digitorum longus muscle group, dichlorphenamide increased the force significantly by 30%, but both drugs failed to increase resistance of muscle fibres to eccentric contractions. Histological analysis revealed a reduction of centrally nucleated fibers in M. tibialis anterior and diaphragm in the treated groups. These studies further demonstrated that a C. elegans-based screen coupled with a mouse model validation strategy can lead to the identification of potential pharmacological agents for rare diseases.