Jennifer Hong

Neuronal and epithelial cell rescue resolves chronic systemic inflammation in the lipid storage disorder Niemann-Pick C

Chronic systemic inflammation is thought to be a major contributor to metabolic and neurodegenerative diseases. Since inflammatory components are shared among different disorders, targeting inflammation is an attractive option for mitigating disease. To test the significance of inflammation in the lipid storage disorder (LSD) Niemann-Pick C (NPC), we deleted the macrophage inflammatory gene Mip1a/Ccl3 from NPC diseased mice. Deletion of Ccl3 had been reported to delay neuronal loss in Sandhoff LSD mice by inhibiting macrophage infiltration. For NPC mice, in contrast, deleting Ccl3 did not retard neurodegeneration and worsened the clinical outcome. Depletion of visceral tissue macrophages also did not alter central nervous system (CNS) pathology and instead increased liver injury, suggesting a limited macrophage infiltration response into the CNS and a beneficial role of macrophage activity in visceral tissue. Prevention of neuron loss or liver injury, even at late stages in the disease, was achieved through specific rescue of NPC disease in neurons or in liver epithelial cells, respectively. Local epithelial cell correction was also sufficient to reduce the macrophage-associated pathology in lung tissue. These results demonstrate that elevated inflammation and macrophage activity does not necessarily contribute to neurodegeneration and tissue injury, and LSD defects in immune cells may not preclude an appropriate inflammatory response. We conclude that inflammation remains secondary to neuronal and epithelial cell dysfunction and does not irreversibly contribute to the pathogenic cascade in NPC disease. Without further exploration of possible beneficial roles of inflammatory mediators, targeting inflammation may not be therapeutically effective at ameliorating disease severity.

Neurostimulation for Neck Pain and Headache

Patients with medically refractory headache disorders are a rare and challenging‐to‐treat group. The introduction of peripheral neurostimulation (PNS) has offered a new avenue of treatment for patients who are appropriate surgical candidates. The utility of PNS for headache management is actively debated. Preliminary reports suggested that 60‐80% of patients with chronic headache who have failed maximum medical therapy respond to PNS. However, complications rates for PNS are high. Recent publication of 2 large randomized clinical trials with conflicting results has underscored the need for further research and careful patient counseling. In this review, we summarize the current evidence for PNS in treatment of chronic migraine, trigeminal autonomic cephalagias and occipital neuralgia, and other secondary headache disorders.

IMAGES IN CLINICAL MEDICINE. Resolution of Lumbar Disk Herniation without Surgery.

A 29-year-old woman presented to the spine clinic with pain in her right leg, accompanied by paresthesia. MRI of the lumbar spine revealed a lumbar disk herniation resulting in substantial spinal stenosis and nerve-root compression.

The Surgical Treatment of Headache

Medically refractory headache is an uncommon but difficult‐to‐treat clinical problem. Patients who fail maximal medical management may be candidates for invasive treatment. In this review, we critically examine the literature on the range of surgical treatments currently available for migraine, trigeminal autonomic cephalalgias, idiopathic intracranial hypertension and Chiari malformation type 1, with particular attention to patient selection, treatment efficacy, and complications.

Prehospital Glasgow Coma Score Predicts Emergent Intervention following Helicopter Transfer for Spontaneous Subarachnoid Hemorrhage.

BACKGROUND Helicopter transport may shorten transport time to neurosurgical intervention; however, there are few data regarding its utility for nontraumatic emergencies. METHODS Prehospital and hospital records of all patients transferred via helicopter to Dartmouth-Hitchcock Medical Center for spontaneous subarachnoid hemorrhage between January 2007 and December 2011 were reviewed. Primary outcome measure was emergent tertiary-level care intervention, defined as ventriculostomy, conventional angiography, endovascular treatment, or craniotomy within 3 hours of arrival. RESULTS Fifty-one patients met inclusion criteria. Median helicopter transport time, defined as time from telephone referral to arrival, was 97 minutes (range, 61-214 minutes). Fifteen patients underwent intervention within 3 hours of arrival (29%), 19 patients underwent intervention between 3 and 6 hours (37%), 9 patients underwent intervention between 6 to 12 hours (18%), and 11 patients underwent intervention greater than 12 hours after arrival (16%). Univariate analysis of pretransfer clinical and radiographic findings showed significant correlations between Glasgow Coma Scale (GCS) score less than 15 (odds ratio [OR], 22.8; 95% confidence interval [CI], 4.2-122.5), World Federation of Neurologic Surgeons (WFNS) scale greater than 2 (OR, 46.75; 95% CI, 7.511-290.99), presence of intraparenchymal hemorrhage (OR, 4.7; 95% CI, 1.3-17.5), and intubation (OR, 12.4; 95% CI, 2.9-51.8) with emergent intervention. On logistic multivariate regression analysis, GCS score less than 15 and WFNS scale score greater than 2 independently predicted emergent intervention. CONCLUSIONS A majority of patients with spontaneous subarachnoid hemorrhage who were transferred by interfacility helicopter ambulance did not require emergent intervention. GCS score less than 15 at an outside hospital was independently associated with emergent intervention on multivariate analysis.

Submammary Placement With Mastopexy for Implantable Pulse Generator Site Pain in Thin Women.

Implantable pulse generators for neurostimulation and other indications are becoming more widespread. Pain at the generator site, erosion through the subcutaneous issues, and migration of the generator are frequent post‐operative complications that result in high rates of re‐operation. We report a case where a submammary combined approach with plastic surgery for improved soft tissue coverage resulted in better esthetic and functional outcomes in a thin woman.

Mini-Open Stabilization of a Sacral Fracture: Technical Case Report

BACKGROUND AND IMPORTANCE: Comminuted sacral fractures present significant challenges for operative management. Open and percutaneous sacroiliac screws have been used for stabilization but carry not insignificant rates of complications, including wound infection for the former and malposition and neurological injury for the latter. We report the use of a novel mini-open lumbar-ilium fixation for stabilization of a patient with a comminuted sacral fracture. CLINICAL PRESENTATION: A 33-year-old man with intact neurologic function was admitted after a fall of approximately 25 ft. A comminuted sacral fracture was diagnosed. The patient was unable to tolerate conservative management because of pain in upright positions. The patient was taken to the operating room for stabilization with a “mini-open” procedure involving L4 and L5 pedicle screws and bilateral iliac screws. Four 2-in paramedian incisions were made overlying the L4-L5 facet joints and medial to the sacroiliac joints. Minimally invasive retractors were placed to expose bony landmarks. L4-L5 pedicle screws and bilateral iliac screws were placed with minimal fluoroscopic guidance. Titanium rods were tunneled inferior-superiorly between incisions and affixed to screw heads. Total operative time was approximately 3.5 hours. The patient remained neurologically intact and had an uncomplicated recovery. One-year follow-up computed tomography showed successful healing of the sacrum. CONCLUSION: We report the first case of a mini-open procedure to treat a comminuted sacral fracture. Use of this procedure offers a straightforward method for sacral stabilization with minimal blood loss and minimal radiation exposure. If indicated, this method could be combined with decompressive procedures. ABBREVIATION: PSIS, posterior superior iliac spine

Prehospital Predictors of Emergent Intervention After Helicopter Transfer for Spontaneous Intraparenchymal Hemorrhage

OBJECTIVE Helicopter transport may shorten transportation times for emergent neurosurgical intervention. The usefulness of helicopter transport after spontaneous intraparenchymal hemorrhage is not well studied. This study seeks to clarify factors that are associated with urgent surgical intervention in patients with spontaneous intracerebral hemorrhage following helicopter transport. METHODS Records were reviewed for patients with spontaneous intraparenchymal hemorrhage transported by helicopter to Dartmouth-Hitchcock Medical Center between January 2008 and December 2011. Records were evaluated for factors associated with emergent tertiary-level care intervention during the first 24 hours of admission. RESULTS A total of 107 patients met inclusion criteria, with a mean age of 67.2 years. At presentation, 79 (75.24%) were hypertensive, 22 (21.57%) had an increased international normalized ratio, and 47 (45.19%) were intubated. Thirty-three patients (30.8%) underwent 1 or more neurosurgical interventions within 24 hours of arrival, with an additional 6 (5.6%) patients undergoing neurosurgical intervention after 24 hours after admission. On univariate analysis, age, Glasgow Coma Scale (GCS) score, and clot volume were significant predictors of neurosurgical intervention within 24 hours of interfacility helicopter transport. A lobar clot, presence of intraventricular hemorrhage, and presence of >1 cm of midline shift were also associated with neurosurgical intervention within 24 hours. On multivariate analysis, younger age, GCS score of 3-8, and lobar hemorrhage were independent predictors of neurosurgical intervention within 24 hours. CONCLUSIONS Two thirds of patients did not undergo any surgical intervention during the first 24 hours of admission after interfacility helicopter transfer. Factors associated with urgent neurosurgical intervention included younger age, low GCS score, and presence of lobar hemorrhage.

A Cohort Study of the Natural History of Odontoid Pseudoarthrosis Managed Nonoperatively in Elderly Patients

OBJECTIVE Although the primary goal of treatment of type II odontoid fracture is bony union, some advocate continued nonsurgical management of minimally symptomatic older patients who have fibrous union or minimal fracture motion. The risk of this strategy is unknown. We reviewed our long-term outcomes after dens nonunion to define the natural history of Type II odontoid fractures in elderly patients managed nonoperatively. METHODS A retrospective chart review of 50 consecutive adults aged 65 or older with Type II odontoid fracture initially managed nonsurgically from 1998 to 2012 at a single tertiary care institution was conducted. Particular attention was paid to patients who had orthosis removal despite absent bony fusion. Patients were contacted prospectively by telephone and followed until death, surgical intervention, or last known contact. RESULTS Fifty patients initially were managed nonsurgically; of these, 21 (42.0%) proceeded to bony fusion, 3 (6%) underwent delayed surgery for persistent instability, and 26 (52%) had orthosis removal despite the lack of solid arthrodesis on imaging. The last group had a median follow-up of 25 months (range 4-158 months), with 20 of 26 (76.9%) followed until death. Of these patients, 1 patient developed progressive quadriplegia and dysphagia 11 months after initial injury. Compared with patients with spontaneous union, patients with nonunion had shorter life expectancy, despite no significant differences between the groups with respect to age, sex, injury mechanism, radiographic variables, or follow-up duration. CONCLUSIONS Orthosis removal despite fracture nonunion may be reasonable in elderly patients with Type II dens fractures.

5-Aminolevulinic Acid-Induced Fluorescence in Focal Cortical Dysplasia: Report of 3 Cases

BACKGROUND Three patients enrolled in a clinical trial of 5-aminolevulinic-acid (5-ALA)-induced fluorescence-guidance, which has been demonstrated to facilitate intracranial tumor resection, were found on neuropathological examination to have focal cortical dysplasia (FCD). OBJECTIVE To evaluate in this case series visible fluorescence and quantitative levels of protoporphyrin IX (PpIX) during surgery and correlate these findings with preoperative magnetic resonance imaging (MRI) and histopathology. METHODS Patients were administered 5-ALA (20 mg/kg) approximately 3 h prior to surgery and underwent image-guided, microsurgical resection of their MRI- and electrophysiologically identified lesions. Intraoperative visible fluorescence was evaluated using an operating microscope adapted with a commercially available blue light module. Quantitative PpIX levels were assessed using a handheld fiber-optic probe and a wide-field imaging spectrometer. Sites of fluorescence measurements were co-registered with both preoperative MRI and histopathological analysis. RESULTS Three patients with a pathologically confirmed diagnosis of FCD (Types 1b, 2a, and 2b) underwent surgery. All patients demonstrated some degree of visible fluorescence (faint or moderate), and all patients had quantitatively elevated concentrations of PpIX. No evidence of neoplasia was identified on histopathology, and in 1 patient, the highest concentrations of PpIX were found at a tissue site with marked gliosis but no typical histological features of FCD. CONCLUSION FCD has been found to be associated with intraoperative 5-ALA-induced visible fluorescence and quantitatively confirmed elevated concentrations of the fluorophore PpIX in 3 patients. This finding suggests that there may be a role for fluorescence-guidance during surgical intervention for epilepsy-associated FCD.