Citations

AbstractThe porphyrias are a group of disorders characterized by defects in the heme biosynthesis pathway. Many present with skin findings including photosensitivity, bullae, hypertrichosis, and scarring. Systemic symptoms may include abdominal pain, neuropsychiatric changes, anemia, and liver disease. With advances in DNA analysis, researchers are discovering the underlying genetic causes of the porphyrias, enabling family members to be tested for genetic mutations. Here we present a comprehensive review of porphyria focusing on those with cutaneous manifestations. In Part I, we have included the epidemiology, pathogenesis, presentation, diagnosis, and histopathology. Treatment and management options will be discussed in Part II.

The decision to treat a patient with therapeutic apheresis depends on multiple factors, such as what does the patient most likely have, is the diagnosis amenable to apheresis treatment, what is the harm‐versus‐benefit ratio of apheresis treatment in this patient, and what are the internal and external issues associated with receiving apheresis treatment? The “ G uidelines on the U se of T herapeutic A pheresis in C linical P ractice— E vidence‐based A pproach from the Writing C ommittee of the A merican S ociety for A pheresis” addresses these issues and helps aid in clinical decision making. The development and application of these G uidelines as well as potential new applications will be discussed in this article.

Polymyalgia rheumatica (PMR) is a common inflammatory condition that often affects people over the age of 50 years. Characteristic symptoms are shoulder and hip girdle pain and prolonged morning stiffness. Markers of inflammation are often elevated. Clinicians are often faced with the challenge of distinguishing PMR from other conditions, particularly rheumatoid arthritis and spondyloarthropathy that can mimic symptoms of PMR in older people. Additionally, there is an association between PMR and giant cell arteritis, a common large-vessel vasculitis which also affects people over the age of 50 years. Imaging of the large vessels in asymptomatic patients with PMR often reveals findings of subclinical vasculitis. Presently, there are no tests that are specific for the diagnosis of PMR and clinicians rely on a combination of history, physical examination, laboratory tests and imaging studies to make a diagnosis. A recent undertaking by the European League Against Rheumatism/American College of Rheumatology has led to the publication of provisional classification criteria of PMR. Ultrasonography, which is being increasingly used by rheumatologists, can greatly aid in the diagnosis of PMR and often shows changes of synovitis and tenosynovitis. Treatment consists of low doses of glucocorticoids which are associated with morbidity. Evaluation of newer biologic therapies targeting inflammatory cytokines is underway. Despite treatment, relapses are common.

Objective To highlight the occurrence of spontaneous cerebrospinal fluid ( CSF ) leak in the setting of K lippel– T renaunay– W eber syndrome ( KTWS ). Background KTWS is a congenital multicomponent disorder of angiogenesis plus limb asymmetry. The cause of spontaneous CSF leaks often remains unknown, but the notion of a pre‐existing dural weakness related to a disorder of connective tissue matrix is gaining momentum. Report of Cases and Methods Two women with KTWS developed spontaneous CSF leaks. Each underwent extensive head and spine imaging studies. One patient underwent surgery to treat the CSF leak and later an epidural blood patch upon partial recurrence of her symptoms. The other patient, who had intermittent CSF leak, developed cerebral venous thrombosis requiring several months of anticoagulation therapy. Both patients have histories of visceral bleeding: gastrointestinal in 1 patient and genitourinary in the other. Results The predominant site of vascular anomaly was the left lower limb in 1 patient and the right upper limb in the other, while the involved limb was larger in 1 patient and smaller in the other. Each patient presented with orthostatic headaches. One had additional choreiform movements and cognitive difficulties that responded to the treatment of the leak. Head magnetic resonance imaging in both patients showed diffuse pachymeningeal enhancement and evidence of sinking of the brain. Computed tomography myelography in 1 patient disclosed the site of the leak; and she underwent surgery to treat the leak, and later an epidural blood patch upon partial recurrence of her symptoms to which she responded well. The other patient had intermittent leak with history of long remission and was reluctant to go through invasive diagnostic or therapeutic measures. Conclusion The occurrence of an uncommon disorder (spontaneous CSF leak) in the setting of a rare congenital disorder in 2 unrelated patients is intriguing. Whether this represents coincidence or a link is not clear but deserves further observations and investigation.

AbstractIntrathecal drug delivery systems (IDDSs) are used to treat resistant pain states as well as intractable spasticity via medication delivery into the spinal fluid. Risks associated with implantation of these devices include infection, bleeding, intrathecal granuloma formation, and neurologic sequelae similar to other neuraxial procedures. Intrathecal catheter placement creates the additional risk of persistent spinal fluid leak, which can lead to postdural puncture headaches as well as seroma formation and may require subsequent surgical exploration or explantation. This retrospective case series examines 3 patients at a single institution with persistent spinal fluid leak after IDDS placement (and explantation in one case) resulting in headache and/or seroma formation that were treated with epidural fibrin glue.Three patients underwent IDDS implantation with baclofen for spasticity. In 1 patient, a cerebral spinal fluid leak developed at 1‐week postoperatively. After several unsuccessful epidural blood patches and surgical exploration with a catheter revision, she was ultimately treated successfully with a fibrin glue patch. The second patient received an IDDS and did well until a seroma developed 1 year later. He was likewise treated with an epidural fibrin glue patch after 2 failed blood patches. In a third patient, a spinal fluid leak developed after explantation of an IDDS and was treated with an epidural fibrin glue patch as initial therapy.

ABSTRACTIntroductionAll descriptions of the Lambert–Eaton syndrome are based on symptomatic patients. We incidentally encountered electromyographic evidence of this syndrome in a patient being studied for another reason. The patient had controlled hypothyroidism and smoked for 9 pack‐years but never had symptoms of weakness or had evidence of cancer. Methods: Detailed electrophysiological and serological evaluations were undertaken in this study. Results: Neuromuscular transmission tests were consistent with a presynaptic disorder. Autoantibodies specific for P/Q‐type voltage‐gated calcium channels (VGCC) were detected in the serum and persisted throughout 7 years of follow‐up. Multiple IgG markers of thyrogastric autoimmunity also were detected. Conclusions: This demonstration of asymptomatic Lambert–Eaton syndrome persisting for 8 years provided novel insight into the natural history of the disorder. It is plausible that patients with a subclinical syndrome would have abrupt neuromuscular decompensation when challenged with medications that compromise the safety factor for synaptic transmission. Muscle Nerve 49: 764–767, 2014

AbstractBackground & AimsC‐Jun N‐terminal kinase (JNK) activation is pivotal in the development of nonalcoholic steatohepatitis (NASH). Mixed lineage kinase 3 (MLK) 3 is one of the mitogen activated protein kinase kinase kinase (MAP3K) that mediates JNK activation in the liver. Despite this concept, the role of MLK3 in modulating liver injury during nutrient excess has not been explored. Our aim was to determine if MLK3 deficient mice were protected against high fat high carbohydrate (HFHC) diet‐induced NASH.MethodsWe employed eight‐week‐old Mlk3−/− male C57BL/6J mice, and wild type (WT) mice C57BL/6J as controls. Mice were fed a HFHC or a chow diet adlib for 16 weeks.ResultsHepatic JNK activating phosphorylation was readily absent in the Mlk3−/− mice fed the HFHC diet, but not in WT mice. This inhibition of JNK activation was hepatoprotective. Despite a comparable increase in weight gain, hepatic steatosis by histological examination and hepatic triglyceride quantification was reduced in HFHC diet‐fed Mlk3−/− mice compared with WT mice. In addition, compared with the WT mice, HFHC diet‐fed Mlk3−/− mice had significantly attenuated liver injury as manifested by reduced ALT levels, hepatocyte apoptosis, markers of hepatic inflammation and indices of hepatic fibrogenesis.ConclusionOur results suggest that loss of MLK3 in mice is protective against HFHC diet‐induced NASH, in a weight‐independent fashion, through attenuation of JNK activation. MLK3 is a potential therapeutic target for the treatment of human NASH.

ObjectiveTo examine the impact of body mass index, as a measure of obesity, on the surgical outcomes of cystectomy.MethodsThe American College of Surgeons National Surgical Quality Improvement Program database was used to acquire data on 1293 cystectomies carried out from 2005 to 2011. Patients were divided into two groups: body mass index <30 kg/m2 and ≥30 kg/m2. A propensity score‐matched analysis of perioperative outcomes was carried out.ResultsA total of 869 patients had a body mass index <30, whereas 424 had a body mass index ≥30. Unadjusted comparisons showed higher rates of superficial surgical site infections (8.7% vs 5.3%, P = 0.04), renal insufficiency (4.0% vs 1.7%, P = 0.01) and increased operative times (365.7 min vs 338.6 min, P = 0.0004) in the obese patients, but interestingly lower rates of pneumonia (2.4% vs 4.8, P = 0.03) and cerebral vascular accidents (0.0% vs 0.9%, P = 0.05). However, the latter two observations might be explained by more tobacco use among non‐obese patients (26.6 mean pack‐years vs 20.0 mean pack‐years, P = 0.004). Notably, no differences in 30‐day mortality were noted. After adjusting for preoperative demographic and clinical data using propensity score‐matching methods, there were no observed differences between the two cohorts except for operative time (P = 0.04).ConclusionsObesity is not independently associated with an increased risk of perioperative complications or 30‐day mortality after cystectomy.