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Background and ObjectiveMyotonic dystrophy types 1 and 2 are progressive multisystem genetic disorders whose core clinical feature is myotonia. Mexiletine, an antagonist of voltage-gated sodium channels, is a recommended antimyotonic agent in the nondystrophic myotonias, but its use in myotonic dystrophy is limited because of lack of data regarding its long-term efficacy and safety profile.MethodsTo address this issue, this study retrospectively evaluated patients with myotonic dystrophy receiving mexiletine over a mean time period of 32.9 months (range 0.1–216 months).ResultsThis study demonstrated that 96% of patients reported some improvement in myotonia symptoms with mexiletine treatment. No clinically relevant cardiac adverse events were associated with the long-term use of mexiletine.ConclusionsThese findings support that mexiletine is both safe and effective when used long-term in myotonic dystrophy.Classification of EvidenceThis study provides Class IV evidence that mexiletine is a well-tolerated and effective treatment for myotonic dystrophy types 1 and 2.

Umhlatuzana rockshelter has an occupation sequence spanning the last 70,000 years. It is one of the few sites with deposits covering the Middle to Later Stone Age transition (~40,000–30,000 years BP) in southern Africa. Comprehending the site’s depositional history and occupation sequence is thus important for the broader understanding of the development of Homo sapiens’ behavior. The rockshelter was first excavated in the 1980s by Jonathan Kaplan. He suggested that the integrity of the late Middle Stone Age and Later Stone Age sediments was compromised by large-scale sediment movement. In 2018, we initiated a high-resolution geoarchaeological study of the site to clarify the site formation processes. Here, we present the results of the excavation and propose a revised stratigraphic division of the Pleistocene sequence based on field observations, sedimentological (particle size) analyses, and cluster analysis. The taphonomy of the site is assessed through phytolith and geochemical (pH, loss on ignition, stable carbon isotope) analyses. The results indicate a consistent sedimentological environment characterized by in situ weathering. The analysis of the piece-plotted finds demonstrates semihorizontal layering of archaeologically dense zones and more sterile ones. There was no indication of large-scale postdepositional sediment movement. We show that the low-density archaeological horizons in the upper part of the Pleistocene sequence are best explained by the changing patterns of sedimentation rate.

ObjectivesHereditary Transthyretin (ATTR) amyloidosis is a genetic disorder where insoluble amyloid fibrils deposit in heart, nerves and various musculoskeletal tissues. Early recognition of TTR-FAP is important as new genetic therapies become available.DesignWe present one confirmed and one clinical case of ATTR deposition in ligamentum flavum causing lumbar canal stenosis.SubjectsThe first case is a 44-year-old female with TTR 184S heterozygous mutation who developed urinary urgency and bilateral leg pain exacerbated by walking. Neurological examination was normal. MRI lumbar spine showed a disc bulge in combination with ligamentum flavum thickening at L2/3 causing stenosis of the vertebral canal. She had a laminectomy of the L2/3 level. Histopathological analysis of the surgical tissue was positive on Congo red staining for amyloid and immunohistochemically identified as TTR type. The second case is a 68-year-old man with TTR V122I heterozygous mutation. He presented with paraesthesia from the knees to dorsum of the feet. On examination, power was normal and he had a length dependent neuropathy. A CT myelogram demonstrated spondylosis at L4/5 and L3/4 from disc bulge and marked flaval hypertrophy causing canal stenosis. He was placed on the waitlist for L4-5 decompression but unfortunately died prior to surgery.ConclusionsIdentifying ATTR in surgical specimens may diagnose hereditary amyloidosis in otherwise asymptomatic patients and in the future, provide early access to effective therapies.

BackgroundABN immunoglobulin (Ig) guidelines advise routine FBC and U and E monitoring with every treatment episode and screening for IgA deficiency. AimsWe audited compliance in inflammatory neuropathy patients on longterm treatment in two UK Neurology departments. We looked for evidence of clinically relevant haematological or AKI Ig-related events.MethodsData was collected from Nov 2015 to Nov 2017. Accepted definitions for clinically and/or biochemically significant haemolysis, neutropenia, thrombocytopenia and AKI were used.Results1919 treatment episodes in 90 patients were analysed. Mean age (SD)=57.6 (14.4)years, 69.1% male, 74% CIDP (26% MMN), 94% IVIg (6% SCIg). Mean dose=1.57 (0.74) g/kg/month or 97.1 (37.3) g/infusion. No clinically significant episodes of haemolysis, neutropenia, thrombocytopenia or AKI occurred in relation to Ig treatment. An asymptomatic drop of >10 g/L Hb occurred in 68/1919 episodes in 38 individuals (3.5%); mean reduction 17.7 g/L, lowest Hb 99 g/L. Two patients with CRF (stage 3) received 28 (IV) and 104 (SC) infusions respectively without impact on eGFR. Two individuals with relative IgA deficiency (0.38 g/L, 0.4 g/L) received 16 infusions over 1.5 years without complications.ConclusionsNo clinically significant Ig-related events were identified in this representative cohort. We suggest annual screening or clinically indicated testing as safe and more appropriate in longterm IVIg use.

No doubt exists that information technology is emerging as a key resource in the purchasing process. Concurrently, buyer-supplier relationships are changing. The purpose of this research is to determine if there is a relationship between the use of information technology and buyer-supplier relationships. A brief review of the literature on the use of information technology in purchasing is provided. Next, the nature of buyer-supplier relationships is discussed. Triangulation-involving field interviews followed by a mail survey-was used to collect data and attempt to answer the three research questions. The three questions were the following. (1) What is the relationship between the use of information technology and frequency of information shared between buyers and suppliers? (2) What is the relationship between the use of information technology and the richness of information shared between buyers and suppliers? (3) What is the relationship between the use of information technology and buyer-supplier trust? Information technology is defined in terms of automated purchasing systems, supplier links via electronic data interchange, information systems and computer-to-computer links with key suppliers. The research results suggest that three of the different types of information technology were significantly related to the frequency of information shared among buyers. Two of the different types of information technology were significantly related to the richness of information shared. However, only one of the types of information technology appears to be significantly related to trust among buyers and suppliers.

Background Observational data suggest intravenous immunoglobulin (IVIg) increases risk of thromboembolic events (TEE). Traditional vascular risk factors influence individual risk but the pro-coagulant mechanism of IVIg is not understood. Aims To ascertain frequency of and risk factors for arterial (ATE) and venous thromboembolic events (VTE) in neuromuscular patients receiving regular IVIg. Methods Diagnosis, dose, frequency, vascular risk factors, pre and post-treatment IgG levels and plasma viscosity were recorded by retrospective casenote review. Results 112 patients received a mean (S.D) dose of 1.6 (1.2)g/kg/month, range:0.2–6.5 g/kg/month; at a mean (S.D.) interval of 4.4 (3.0) weeks, range:1–18 weeks for CIDP (58.9%), MMN (36.6%), sensory neuropathy/neuronopathy (3.7%) and myositis (0.9%). Twelve TEEs were documented during the 30 month study period (January ‘14-June ‘16); 6 MIs, 2 CVAs, and individual occurrences of TIA, DVT, PE, SVC obstruction due to central line thrombosis. TEE incidence (95% C.I.)=53.6 (30.9, 91.3)/1000 patient-years; ATE incidence=35.7 (18.2, 68.9)/1000 patient-years; VTE=22.3 (9.6–51.2)/1000 patient-years. Age (p=0.005) and QRISK2 score (p=0.01) were higher in those who had an event. There was no difference in dose/kg/month (p=0.66), or dose/g/day (p=0.28). Conclusions TEE incidence in this cohort was higher than population-based rates (TEE=7.6–7.7/1000; ATE=4.4–6.5/1000 and VTE=1.2/1000 patient-years). This analysis suggests reduction of daily dose or rate of infusion does little to mediate risk.

We report a 63 year old lady with decreased visual acuity, no wrinkles and difficulty sucking drinks through a straw. Neurological examination revealed bilateral lower motor neuron facial weakness. There was normal tone and power in the limbs and pinprick, temperature and proprioception were intact but vibration sensation was absent to the level of the sternum. Gait was normal but there was mild clumsiness of the hands. No prior family history of neurological disease was known. Electrophysiology revealed normal sensory action potentials. Ophthalmological examination prompted the diagnosis of hereditary gelsolin amyloidosis which is recognized by the triad of corneal lattice dystrophy, progressive cranial neuropathy and cutis laxa. This was confirmed on finding a heterozygous D241N Gelsolin mutation. The unusual pattern of dissociated vibration and proprioceptive loss has been described in this condition with histopathological amyloid deposition providing eloquent demonstration of the involved anatomy. We present this rare case as an interesting and educational lesson in spinal cord anatomy.

Introduction Hereditary transthyretin-related amyloidosis (ATTR) is a genetically heterogenous disease which may present with a predominant peripheral and autonomic neuropathy, a cardiac myopathy, or with both neurological and cardiac involvement. The V122I variant has a frequency of 3–4% in African Americans and causes 11% of cardiomyopathy in this population. Isolated cardiomyopathy is the typical presentation. Methods Here we present the clinical, electrophysiological, nuclear imaging and histological findings of an unusual case of V122I ATTR. Results A 64 year old Jamaican man presented with cardiac failure. Cardiac MR revealed an infiltrative cardiomyopathy; abdominal fat aspirate confirmed the presence of amyloid and a homozygous V122I mutation in the transthyretin gene were identified. He also described positive sensory symptoms in his feet and general, non-specific weakness; NCS showed length-dependant axonal neuropathy and EMG demonstrated some myopathic features. Amyloid deposits were seen on sural nerve and vastus lateralis biopsies. The patient is being treated with diflunasil, an oral agent with in vitro evidence for TTR stabilization. Conclusion Symptomatic neuropathy or myopathy with morphological confirmation of tissue amyloid deposition has not been previously described with this mutation. The presence of extracardiac amyloidosis impacted on diagnostic and treatment options in this case.