Mumps encephalitis with akinesia and mutism

Measles‐rubella‐mumps vaccination is routine in many countries, but the mumps vaccine remains voluntary and is not covered by insurance in Japan. A 5‐year‐old Japanese boy who had not received the mumps vaccine was affected by mumps parotitis. Several days later, he presented with various neurological abnormalities, including akinesia, mutism, dysphagia, and uncontrolled respiratory disorder. Mumps encephalitis was diagnosed. Despite steroid pulse and immunoglobulin treatment, the disease progressed. Magnetic resonance imaging showed necrotic changes in bilateral basal ganglia, midbrain, and hypothalamus. At 1 year follow up, he was bedridden and required enteral feeding through a gastric fistula and tracheostomy. Mumps vaccination should be made routine as soon as possible in Japan, because mumps encephalitis carries the risk of severe sequelae.     

A new cell‐free bandage‐type artificial skin for cutaneous wounds

Engineered skin substitutes are widely used in skin wound management. However, no currently available products satisfy all the criteria of usability in emergency situations, easy handling, and minimal scar formation. To overcome these shortcomings, we designed a cell‐free bandage‐type artificial skin, named “VitriBand” (VB), using adhesive film dressing, silicone‐coated polyethylene terephthalate film, and collagen xerogel membrane defined as a dried collagen vitrigel membrane without free water. We analyzed its advantages over in‐line products by comparing VB with hydrocolloid dressing and collagen sponge. For evaluation, mice inflicted with full‐thickness skin defects were treated with VB, hydrocolloid dressing, and collagen sponge. A plastic film group treated only with adhesive film dressing and silicone‐coated polyethylene terephthalate film, and a no treatment group were also compared. VB promoted epithelization while inhibiting the emergence of myofibroblasts and inflammation in the regenerating tissue more effectively than the plastic film, hydrocolloid dressing, and collagen sponge products. We have succeeded in establishing a cell‐free bandage‐type artificial skin that could serve as a promising first‐line medical biomaterial for emergency treatment of skin injuries in various medical situations.     

Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open‐label,phase 3 trial

Genotype 2 hepatitis C virus (HCV) accounts for up to 30% of chronic HCV infections in Japan. The standard of care for patients with genotype 2 HCV – peginterferon and ribavirin for 24 weeks – is poorly tolerated, especially among older patients and those with advanced liver disease. We conducted a phase 3, open‐label study to assess the efficacy and safety of an all‐oral combination of the NS5B polymerase inhibitor sofosbuvir and ribavirin in patients with chronic genotype 2 HCV infection in Japan. We enrolled 90 treatment‐naïve and 63 previously treated patients at 20 sites in Japan. All patients received sofosbuvir 400 mg plus ribavirin (weight‐based dosing) for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after therapy (SVR12). Of the 153 patients enrolled and treated, 60% had HCV genotype 2a, 11% had cirrhosis, and 22% were over the aged 65 or older. Overall, 148 patients (97%) achieved SVR12. Of the 90 treatment‐naïve patients, 88 (98%) achieved SVR12, and of the 63 previously treated patients, 60 (95%) achieved SVR12. The rate of SVR12 was 94% in patients with cirrhosis and in those aged 65 and older. No patients discontinued study treatment due to adverse events. The most common adverse events were nasopharyngitis, anaemia and headache. Twelve weeks of sofosbuvir and ribavirin resulted in high rates of SVR12 in treatment‐naïve and previously treated patients with chronic genotype 2 HCV infection. The treatment was safe and well tolerated by patients, including the elderly and those with cirrhosis.     

Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice

Prolyl endopeptidase (PREP) has been implicated in neuronal functions. Here we report that hypothalamic PREP is predominantly expressed in the ventromedial nucleus (VMH), where it regulates glucose-induced neuronal activation. PREP knockdown mice (Prep^gt/gt) exhibited glucose intolerance, decreased fasting insulin, increased fasting glucagon levels, and reduced glucose-induced insulin secretion compared with wild-type controls. Consistent with this, central infusion of a specific PREP inhibitor, {"type":"entrez-protein","attrs":{"text":"S17092","term_id":"94591","term_text":"pir||S17092"}}S17092, impaired glucose tolerance and decreased insulin levels in wild-type mice. Arguing further for a central mode of action of PREP, isolated pancreatic islets showed no difference in glucose-induced insulin release between Prep^gt/gt and wild-type mice. Furthermore, hyperinsulinemic euglycemic clamp studies showed no difference between Prep^gt/gt and wild-type control mice. Central PREP regulation of insulin and glucagon secretion appears to be mediated by the autonomic nervous system because Prep^gt/gt mice have elevated sympathetic outflow and norepinephrine levels in the pancreas, and propranolol treatment reversed glucose intolerance in these mice. Finally, re-expression of PREP by bilateral VMH injection of adeno-associated virus–PREP reversed the glucose-intolerant phenotype of the Prep^gt/gt mice. Taken together, our results unmask a previously unknown player in central regulation of glucose metabolism and pancreatic function.Prolyl endopeptidase (PREP; EC 3.4.21.26) is a highly conserved enzyme (1). In humans and rodents it is highly expressed in the brain (2), including the cortex, striatum, hypothalamus, hippocampus, and amygdala (3–6). The physiological role of PREP remains elusive (7). Many studies have focused on the putative effect of PREP on neuropeptide levels because this enzyme could function to cleave virtually all neuropeptides shorter than 30 amino acids that contain an internal proline residue (8).However, much of our understanding of this enzyme is based on in vitro data. Because PREP’s putative targets regulate a large number of signaling pathways, PREP has the capacity to regulate a variety of cellular tasks.To gain a better understanding of the role of PREP in the hypothalamus, we analyzed the effect of PREP knockdown on hypothalamic mechanisms including glucose and energy metabolism.     

Early awareness of cerebrospinal fluid hypovolemia after craniotomy for microsurgical aneurysmal clipping

Background

Mild cerebrospinal fluid (CSF) hypovolemia is a well-known clinical entity, but critical CSF hypovolemia that can cause transtentorial herniation is an unusual and rare clinical entity that occurs after craniotomy. We investigated CSF hypovolemia after microsurgical aneurysmal clipping for subarachnoid hemorrhage (SAH).

Method

This study included 144 consecutive patients with SAH. Lumbar drainage (LD) was inserted after general anesthesia or postoperatively as a standard perioperative protocol. CSF hypovolemia diagnosis was based on three criteria.

Results

Eleven patients (7.6 %) were diagnosed with CSF hypovolemia according to diagnostic criteria in a postoperative range of 0–8 days. In all patients, signs or symptoms of CSF hypovolemia improved within 24 hours by clamping LD and using the Trendelenburg position.

Conclusions

As a cause of acute clinical deterioration after aneurysmal clipping, CSF hypovolemia is likely under-recognized, and may actually be misdiagnosed as vasospasm or brain swelling. We should always take the etiology of CSF hypovolemia into consideration, and especially pay attention in patients with pneumocephalus and subdural fluid collection alongside brain sag on computed tomography. These patients are at higher risk developing of pressure gradients between their cranial and spinal compartments, and therefore, brain sagging after LD, than after ventricular drainage. We should be vigilant to strictly manage LD so as not to produce high pressure gradients.