Rare manifestation of a c.290 C\u3eT, p.Gly97Glu VCP mutation

Introduction. The valosin-containing protein (VCP) regulates several distinct cellular processes. Consistent with this, VCP mutations manifest variable clinical phenotypes among and within families and are a diagnostic challenge. Methods. A 60-year-old man who played ice hockey into his 50’s was evaluated by electrodiagnostics, muscle biopsy, and molecular genetics. Results. With long-standing pes cavus and toe walking, our patient developed progressive weakness, cramps, memory loss, and paresthesias at age 52. An axonal sensorimotor neuropathy was found upon repeated testing at age 58. Neuropathic histopathology was present in the quadriceps, and exome sequencing revealed the VCP mutation c.290 C>T, p.Gly97Glu. Conclusions. Our patient reflects the clinical heterogeneity of VCP mutations, as his neurological localization is a spectrum between a lower motor neuron disorder and a hereditary axonal peripheral neuropathy such as CMT2. Our case demonstrates a rare manifestation of the c.290 C>T, pGly97Glu VCP mutation

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

T118M Variant of PMP22 Gene Presents with Painful Peripheral Neuropathy and Varying Charcot-Marie-Tooth Features: A Case Series and Review of the Literature

The clinical effect of T118M variant of the PMP22 gene has been controversial. Several studies have suggested that it may be autosomal recessive, partial loss of function, or a benign variant. Here we report three cases in further support that the T118M variant of the PMP22 gene is a partial loss of function variant. These three unrelated cases were heterozygotes with the T118M variant of the PMP22 gene. All three cases presented with painful peripheral neuropathy and varying degrees of Charcot-Marie-Tooth exam features. Electrophysiological studies revealed polyneuropathy with axonal and demyelinating features in one case, but there were minimal electrophysiological changes in the other two cases. We propose that the T118M variant can cause painful peripheral neuropathy, which may be an underrecognized feature of this variant

V144D Mutation of SPTLC1 Can Present with Both Painful and Painless Phenotypes in Hereditary Sensory and Autonomic Neuropathies Type I

Hereditary sensory and autonomic neuropathy type I (HSAN I) is an autosomal dominant disease characterized by distal sensory loss, pain insensitivity, and autonomic disturbances. The major underlying causes of HSAN I are point mutations in the SPTLC1 gene. Patients with mutations in the SPTLC1 genes typically exhibit dense sensory loss and incidence of lancinating pain. Although most of these mutations produce sensory loss, it is unclear which mutations would lead to the painful phenotype. In this case series, we report that the V144D mutation in SPTLC1 gene may relate to both painful and painless peripheral neuropathies. The unique clinical phenotype of this mutation may guide clinical workup and treatment for patients with painful and painless neuropathies

Coexistence of a T118MPMP22missense mutation and chromosome 17 (17p11.2-p12) deletion

Wahyu Cahyo Nugroho, 2020, “Analisa Pengaruh Perbaikan Sambungan Las Sudut T Tunggal Pada Handguard Dan Footring Dengan Tabung LPG 3 Kg Terhadap Sifat Mekanis Dan Biaya Produksi Pengelasan”, Laporan Skripsi Teknik Mesin Fakultas Teknik Universitas Pancasakti Tegal 2020. Pengujian dan pemeriksaan didalam industri logam, permesinan dan manufaktur dapat dibagi dalam dua kelas, yaitu pengujian dan pemeriksaan untuk keperluan pembuat dan pengujian serta pemeriksaan untuk keperluan pemakai. Pengujian dan pemeriksaan konstruksi las pada handguard dan footringdengan tabung LPG 3 kg memberikan penjelasan mengenai jaminan mutu produk dan konstruksi las yang dimana syarat utamanya merupakan kekuatan las yaitu kekuatan tarik dan tekan. Pada pengujian ini dilakukan pengujian merusak terhadap model dari konstruksi atau pada spesimen uji yang telah dilas sampai terjadi kerusakan pada spesimen uji tersebut. Objek pengujian penelitian ini dilakukan pada sambungan las handguard dan footringdengan tabung LPG 3 kg . Handguard dan Footringmerupakan baja canai panas untuk konstruksi umum JIS G 3101 SS42, tebal 2,5 sampai 3 mm yang disuplai dari PT Krakatau Steelsesuai dengan SNI 07-0722-1989. Kode G pada kode bahan diambil dari standar JIS (Japanese Industrial Standards) yaitu standar baja yang digiling pada temperatur panas (hot rolled steel sheet) khusus digunakan untuk handguard dan footring yang dilas dengan las busur dengan elektroda RD 2.6 E 6013. Pengujian dilakukan dengan cara pengujian tarik sesuai dengan SNI 07-0408-1989 dan pengujian bending/lengkung tekan sesuai dengan SNI 07-0410-1989. Hasil pengujian sambungan las pada handguard dan footring dengan arus 165 A (sesuai industri logam) didapatkan kekuatan tarik rata-rata sebesar 38,893 N/mm². Pada pengujian tekan/ bendingrata-rata sebesar 35,64 N/mm²hingga sudut 180° tidak terjadi adanya pengaruh retakan las (no defeet), serta biaya las perbulan Rp 629.211,33. Metode dalam penelitian ini adalah dengan mengobservasi salah satu sentra industri pengelasan tabung LPG 3 kg di kecamatan Bulakamba kabupaten Brebes dan melakukan variasi pengelasan arus yang digunakan saat pengelasan handguard dan footring tabung LPG 3 kg untuk menemui hasil las yang terbaik dan sesuai standar pengelasan serta biaya produksi pengelasan. Hasil dari penelitian ini menunjukan pada pengelasan handguard dan footring tabung LPG 3 kg dengan arus las 70 A kekuatan tarik rata-rata yaitu 80,77 N/mm² dan kekuatan lengkung rata-rata yaitu 51,56 N/mm², serta biaya las perbulan Rp 266.938,14, arus las 80 A kekuatan tarik rata-rata yaitu 121,25 N/mm² dan kekuatan lengkung rata-rata yaitu 75,71 N/mm², serta biaya las perbulan Rp 305.072,16, arus las 90 A kekuatan tarik rata-rata yaitu 163,25 N/mm² dan kekuatan lengkung rata-rata yaitu 102,93 N/mm², serta biaya las perbulan Rp 345.606,24. Kata kunci : Handguard dan Footring, elektroda RD 2.6 E 6013, arus las, Kekuatan tarik, kekuatan tekan, dan biaya produksi pengelasan

Options in Treating Trigeminal Neuralgia: Experience With 195 Patients.

OBJECTIVE: For patients with medically unresponsive trigeminal neuralgia (TN), surgical options include microvascular decompression (MVD), radiofrequency rhizotomy (RF), and stereotactic radiosurgery (SRS). In an attempt to identify the risks and benefits and cost inherent with each of the three modalities, we performed a retrospective review of our experience with 195 cases of TN treated over the past 15 years. METHODS: Since 2001, 195 patients with previously untreated TN were managed: with MVD in 79, RF in 36, and SRS in 80. All patients reported herein underwent preoperative MRI. Women outnumbered men 122/73 (p=0.045). Follow-up after surgery was 32±46months. RESULTS: The patients qualifying for MVD were generally healthier and younger, with a mean age±SD of 57±14, compared to those undergoing RF (75±15) or SRS (73±13, p CONCLUSION: MVD for TN is the treatment least likely to fail or require additional treatment. Patients who underwent MVD were younger than those undergoing RF or SRS. The highest rate of recurrence of TN was encountered in patients undergoing RF (64%). Facial numbness was least likely to occur with MVD (16%) compared to RF and SRS (50% and 36% respectively)

A neuropathy-associated kinesin KIF1A mutation hyper-stabilizes the motor-neck interaction during the ATPase cycle

The mechanochemical coupling of ATPase hydrolysis and conformational dynamics in kinesin motors facilitates intramolecular interaction cycles between the kinesin motor and neck domains, which are essential for microtubule-based motility. Here, we characterized a charge-inverting KIF1A-E239K mutant that we identified in a family with axonal-type Charcot-Marie-Tooth disease and also in 24 cases in human neuropathies including spastic paraplegia and hereditary sensory and autonomic neuropathy. We show that Glu239 in the beta 7 strand is a key residue of the motor domain that regulates the motor-neck interaction. Expression of the KIF1A-E239K mutation has decreased ability to complement Kif1a(+/-) neurons, and significantly decreases ATPase activity and microtubule gliding velocity. X-ray crystallography shows that this mutation causes an excess positive charge on beta 7, which may electrostatically interact with a negative charge on the neck. Quantitative mass spectrometric analysis supports that the mutation hyper-stabilizes the motor-neck interaction at the late ATP hydrolysis stage. Thus, the negative charge of Glu239 dynamically regulates the kinesin motor-neck interaction, promoting release of the neck from the motor domain upon ATP hydrolysis

Survey of the functional priorities in patients with disability due to neuromuscular disorders

<p><b>Title:</b> Survey of the functional priorities in patients with disability due to neuromuscular disorders.</p> <p><b>Objective:</b> This study attempts to determine the functional priorities for patients with neuromuscular disorders.</p> <p><b>Methods:</b> A survey asking about functional priorities with respect to activities of daily living, ankle foot orthotic design, and assistive device design, was distributed to patients with neuromuscular disorders to assess the needs of patients from their perspectives. Descriptive statistics were used to analyse answers.</p> <p><b>Results:</b> A total of 171 subjects with neuromuscular disorders responded to the questionnaire. Of the respondents with weakness in both the upper and lower extremities, 45% stated that if they had to choose between correction of one or the other, they would prefer that of their lower extremities. Activities that patients most frequently wanted to gain independence with were mobility and transfers (46%), followed by toilet use and hygiene (32%). The most popular control mechanism of an assistive device was voice activation (35%).</p> <p><b>Conclusion:</b> This study assessed the functional priorities of those with neuromuscular disorders. Although such individuals can experience a range of weakness in the upper and/or lower extremities, common functional priorities were reported: independence with mobility, transfers, toilet use and hygiene. Knowledge of these priorities will help guide development of assistive devices that will restore function in the future.Implications for Rehabilitation</p><p>    Neuromuscular Disorders</p><p> • Neuromuscular disorders result in disabling weakness; there are few cures and many are unable to carry out activities of daily living.</p><p> • Information that would be helpful in determining functional priorities is limited.</p><p> • In a survey of 171 patients with neuromuscular disorders, functional priorities included mobility and transfers (46%), followed by toilet use and hygiene (32%).</p><p> • Of the respondents with weakness in both the upper and lower extremities, 45% stated that if they had to choose between correction of one or the other, they would prefer that of their lower extremities.</p><p> • If an assistive device were to be created to help those with neuromuscular disorders, the most popular control mechanism would be voice activation (35%).</p><p></p> <p>    Neuromuscular Disorders</p> <p> • Neuromuscular disorders result in disabling weakness; there are few cures and many are unable to carry out activities of daily living.</p> <p> • Information that would be helpful in determining functional priorities is limited.</p> <p> • In a survey of 171 patients with neuromuscular disorders, functional priorities included mobility and transfers (46%), followed by toilet use and hygiene (32%).</p> <p> • Of the respondents with weakness in both the upper and lower extremities, 45% stated that if they had to choose between correction of one or the other, they would prefer that of their lower extremities.</p> <p> • If an assistive device were to be created to help those with neuromuscular disorders, the most popular control mechanism would be voice activation (35%).</p