Acute spontaneous intracranial epidural haematoma and disseminated intravascular coagulation in a paediatric sickle cell patient.

An African American teenage boy during an acute sickle cell crisis spontaneously developed acute bifrontal epidural haematomas (EDHs) in addition to disseminated intravascular coagulation (DIC). The successfully evacuated EDH reaccumulated postoperatively. After multiple transfusions, the patient underwent repeat surgery. Subsequent maximal medical therapy was unable to significantly improve the patient's neurological status, and due to family wishes, care was withdrawn. EDH are the most common emergent neurosurgical complication of sickle cell disease (SCD). Twenty-two such cases have been previously reported. We present one further complicated by DIC leading to reaccumulation of the patient's EDH. An understanding of the mechanisms of EDH formation in SCD and their associated radiological findings could help clinicians identify when a patient is at high risk of EDH formation and thus offer the potential for early intervention prior to the development of an emergency.

Transection of Omohyoid Muscle as an Aid During Vagus Nerve Stimulator Implantation.

BACKGROUND: Exposure of the carotid sheath during vagus nerve stimulator (VNS) implantation is usually straightforward but can be difficult for patients with a large body habitus. In addition, the exposure must be done with care if the surgeon wants to keep the vagus nerve in situ without using retractors that might impair access. OBJECTIVE: We describe the use of the omohyoid muscle as a landmark for the jugular vein and report how transection of the omohyoid can facilitate rapid and wide exposure of the carotid sheath. METHODS: We review the records of 59 consecutive patients undergoing VNS implantation from 2009-2015 and describe our technique incorporating omohyoid transection. We also summarize complications such as postoperative hoarseness, cough, dysphagia, or wound issues. RESULTS: Forty-two of the 59 patients (29 adults and 13 children) underwent omohyoid transection during implantation. In all cases, the carotid sheath and jugular vein were immediately visible after transection. One patient developed permanent hoarseness and coughing due to left vocal cord paresis, requiring further surgery. This result was most likely due to manipulation of the vagus nerve rather than division of the omohyoid muscle. CONCLUSION: Omohyoid transection provides excellent exposure of the carotid sheath during VNS implantation.

Anterior Gray Matter Pituicytic Heterotopia with Monomorphic Anterior Pituitary Cells: A Variant of Nonsecretory Pituitary Adenoma Neuronal Choristoma? Report of a Rare Case and Review of the Literature.

BACKGROUND: Mixed tumors of adenomatous and neuronal cells in the sellar region are an uncommon finding. The origins of these heterogeneous tumors are unknown, and management remains unsettled. We report a very rare case of anterior gray matter pituicytic heterotopia with monomorphic anterior pituitary cells that likely represents a variant of nonsecreting pituitary adenoma neuronal choristoma (PANCH) with no ganglion cells. We also review the current literature for the various clinical presentations of PANCH. CASE DESCRIPTION: A 49-year-old female complaining of headache, blurred vision, and hair loss was found to have a nonsecretory sellar mass with compression of the optic chiasm on magnetic resonance imaging (MRI). The mass was excised via a transsphenoidal procedure. Histological analysis of tissue sections revealed heterotopic gray matter with reactive gliosis without ganglion cells or Herring bodies. Only 1 smear exhibited characteristics of a pituitary adenoma. CONCLUSIONS: The overall findings were most consistent with a variant of PANCH. At a postoperative follow-up of 4.5 years, there was resolution of visual symptoms, and the residual sellar mass was stable on MRI. Neuronal choristoma is hypothesized to originate from embryonal pituitary or hypothalamus, or by differentiation from pituitary adenoma cells. Surgery is the cornerstone of management, and the clinical course appears to be similar to that of nonfunctioning pituitary adenoma in reported cases.

Intracranial calcified pseudocyst reaction to a shunt catheter.

A 9-year-old boy with spina bifida, Chiari II malformation, and hydrocephalus presented with signs of increased intracranial pressure consistent with a shunt malfunction. Radiological investigations revealed an intracranial calcified lesion along the ventricular catheter. A shunt tap revealed a translucent milky white fluid. The patient underwent a ventriculostomy and, eventually, a shunt revision. Pathology findings were consistent with the formation of dystrophic calcification and a pseudocyst around the shunt catheter. Postoperatively, the patient returned to his neurological baseline. This is, to the best of the authors' knowledge, the first report of an intracranial calcified pseudocyst in a patient with normal renal function.

Effect of antioxidant treatment on spinal GABA neurons in a neuropathic pain model in the mouse.

One feature of neuropathic pain is a reduced spinal gamma-aminobutyric acid (GABA)-ergic inhibitory function. However, the mechanisms behind this attenuation remain to be elucidated. This study investigated the involvement of reactive oxygen species in the spinal GABA neuron loss and reduced GABA neuron excitability in spinal nerve ligation (SNL) model of neuropathic pain in mice. The importance of spinal GABAergic inhibition in neuropathic pain was tested by examining the effects of intrathecally administered GABA receptor agonists and antagonists in SNL and naïve mice, respectively. The effects of SNL and antioxidant treatment on GABA neuron loss and functional changes were examined in transgenic GAD67-enhanced green fluorescent protein positive (EGFP+) mice. GABA receptor agonists transiently reversed mechanical hypersensitivity of the hind paw in SNL mice. On the other hand, GABA receptor antagonists made naïve mice mechanically hypersensitive. Stereological analysis showed that the numbers of enhanced green fluorescent protein positive (EGFP+) GABA neurons were significantly decreased in the lateral superficial laminae (I-II) on the ipsilateral L5 spinal cord after SNL. Repeated antioxidant treatments significantly reduced the pain behaviors and prevented the reduction in EGFP+ GABA neurons. The response rate of the tonic firing GABA neurons recorded from SNL mice increased with antioxidant treatment, whereas no change was seen in those recorded from naïve mice, which suggested that oxidative stress impaired some spinal GABA neuron activity in the neuropathic pain condition. Together the data suggest that neuropathic pain, at least partially, is attributed to oxidative stress, which induces both a GABA neuron loss and dysfunction of surviving GABA neurons.

Indium 111 diethylenetriamine pentaacetic acid scintigraphy in the identification and management of intrathecal pump malfunction.

BACKGROUND: Intrathecal drug-delivery systems have become widely used tools in the management of refractory chronic pain and spasticity. Because increasing numbers of patients are using these systems, rehabilitation specialists frequently are the initial care providers who identify clinical signs and symptoms indicating possible complications relating to the implanted system. Identification of a pump malfunction often presents a diagnostic challenge. Distinguishing among progression of disease, new organic problems, and/or drug-device complications is critical. The use of nuclear medicine indium 111 diethylenetriamine pentaacetic acid (DTPA) studies represents a highly effective, straightforward, minimally invasive way to assess implant function and drug distribution. OBJECTIVE: To identify patients with suspected intrathecal pump malfunction and to determine whether the use of indium 111 DTPA is effective in identifying the source of failure. DESIGN: A retrospective review was performed from 2011 to 2012. SETTING: The study was performed at Georgia Health Sciences University. PATIENTS: The 23 selected patients had implanted devices for either spasticity or pain and were experiencing symptoms of a possible pump malfunction despite normal radiographic imaging. Twenty-four scintigraphic studies were performed, with malfunction documented in 19 patients. METHODS: A standard refill technique was used to inject 0.3 mL of indium 111 DTPA into the pump reservoir. Radionuclide images were reviewed at varying time points up to 48 hours after injection. The extent of radionuclide progression from the pump reservoir to the intrathecal space was evaluated. In cases in which a problem with the implant was identified, correlation with operative findings is described. RESULTS: Normal results of studies ultimately correlated with other clinical issues and confirmed an alternative etiology for the clinical changes noted. In studies with abnormal results, several patterns of failure were identified: restriction of the radionuclide to the pump reservoir, extravasations of tracer into the pump subcutaneous pocket, failure of the tracer to migrate from the subcutaneous catheter to the intrathecal space, and pooling of the tracer in the subcutaneous tissues. In all cases, surgical findings confirmed the suspected mechanism of malfunction as determined by the study. CONCLUSIONS: Indium 111 DTPA scintigraphy is a safe, straightforward way to identify and characterize clinical changes associated with intrathecal drug-delivery systems and to guide appropriate and clinical surgical management.

Reactive oxygen species contribute to neuropathic pain by reducing spinal GABA release.

Although both a loss of spinal inhibitory neurotransmission and the involvement of oxidative stress have been regarded as important mechanisms in the pathogenesis of pain, the relationship between these 2 mechanisms has not been studied. To determine whether reactive oxygen species (ROS) involvement in pain mechanisms is related to the diminished inhibitory transmission in the substantia gelatinosa (SG) of the spinal dorsal horn, behavioral studies and whole-cell recordings were performed in FVB/NJ mice. Neuropathic pain was induced by a tight ligation of the L5 spinal nerve (SNL). Pain behaviors in the affected foot were assessed by behavioral testing for mechanical hyperalgesia. Pain behaviors developed by 3 days and lasted more than 8 weeks. Both systemic and intrathecal administration of an ROS scavenger, phenyl-N-tert-butylnitrone (PBN), temporarily reversed mechanical hyperalgesia up to 2 hours, 1 week after SNL. In nonligated mice, an intrathecal injection of an ROS donor, tert-butyl hydroperoxide (t-BOOH), dose-dependently induced mechanical hyperalgesia for 1.5 hours. In whole-cell voltage clamp recordings of SG neurons, perfusion with t-BOOH significantly decreased the frequency of mIPSCs, and this effect was reversed by PBN. Furthermore, t-BOOH decreased the frequency of GABA(A) receptor-mediated mIPSCs without altering their amplitudes but did not affect glycine receptor-mediated mIPSCs. In SNL mice, mIPSC frequency in SG neurons was significantly reduced as compared with that of normal mice, which was restored by PBN. The antihyperalgesic effect of PBN on mechanical hyperalgesia was attenuated by intrathecal bicuculline, a GABA(A) receptor blocker. Our results indicate that the increased ROS in spinal cord may induce pain by reducing GABA inhibitory influence on SG neurons that are involved in pain transmission.

Protein misfolding disorders and rational design of antimisfolding agents.

Compelling evidence strongly suggests that the conversion of a normal soluble protein into a beta-sheet-rich oligomeric structure and further fibril formation is the critical step in the pathogenesis of several human diseases, termed protein misfolding disorders. Therefore, a promising therapeutic strategy consists of the design of molecules that prevent the misfolding and aggregation of these proteins. In this chapter, we survey the mechanism of protein misfolding and some strategies to rationally produce inhibitors of this process.