Frank P. K. Hsu

Pain and spasticity after spinal cord injury: mechanisms and treatment.

Study Design A comprehensive survey of literature on the proposed mechanisms and treatment of pain and spasticity after spinal cord injury (SCI) was completed. Objectives To define the current understanding of these entities and to review various treatment options. Summary of Background Data. The neurophysiologic basis of spasticity after SCI is well established. The mechanism of neuropathic pain after SCI remains conjectural, although considerable new data, much of it from animal models, now add to our understanding of this condition. Methods. A comprehensive search and review of the published literature was undertaken. Results. Treatment options for spasticity are effective and include oral medication (baclofen, tizanidine), intrathecal baclofen, and rarely, surgical rhizotomy or myelotomy. Selected patients with post–SCI pain can respond to surgical myelotomy (DREZ lesions) or intrathecal agents (e.g., morphine + clonidine), but the majority continue to suffer. Conclusions. Medical and surgical treatments for spasticity are established and highly successful. Management of post-SCI pain remains a clinical challenge, as there is no uniformly successful medical or surgical treatment.

Pedicle screw placement in the thoracic spine: a comparison of image-guided and manual techniques in cadavers.

Study Design. A cadaveric study comparing image guidance technology to fluoroscopic guidance as a means of pedicle screw placement in the thoracic spine, using a unique starting point for screw placement. Objective. To assess accuracy of thoracic pedicle screw placement using image guidance versus fluoroscopic guidance for screw insertion. Summary of Background Data. While use of pedicle screws in the thoracic spine has been increasing, its adoption has been slower than for the lumbar spine, reflecting concern regarding possible vascular or spinal cord injury due to screw malplacement. Given these risks, efforts to improve the accuracy of thoracic pedicle screw placement remain appropriate. Stereotactic guidance has been applied in other aspects of spinal surgery to improve the accuracy of instrumentation placement. Methods. Pedicle screws were placed in the thoracic spines of eight cadavers, using either a stereotactic guidance or a manual, fluoroscopically guided technique. A slightly more superior and lateral starting point from prior descriptions was used. Each cadaver was instrumented with pedicle screws in the upper thoracic (T1–T2), middle thoracic (T4–T7), and lower thoracic (T9–T10) regions. In the upper and middle thoracic regions, screws with a 4.0-mm shank diameter were used while in the lower thoracic region a shank diameter of 4.5 mm was used. Postinstrumentation CT scans, followed by anatomic dissections, were used to evaluate screw exit rates and orientation relative to the pedicle axis. Exit rates for the two techniques and the effect of vertebral level on exit rate were compared using a &khgr;2 analysis. The effect of pedicle diameter was tested using a Pearson correlation coefficient. Results. No significant differences in the overall exit rates or orientation were found between the two techniques. There were significant differences in exit rates between the middle (47%), compared with the upper (9%) and lower (16%) thoracic regions, respectively (P < 0.001). A significant correlation between pedicle diameter and exit rate was also found (P < 0.0001). Conclusion. Our study showed no significant differences in the overall exit rates between the two techniques. Image guidance may increase confidence of surgeons with limited experience in thoracic pedicle screw placement. Successful placement of screws within the pedicle varies with the anatomic diameter of the pedicle itself. Concerns regarding accuracy of screw placement should be greatest in the middle thoracic vertebrae (T4–T7), where pedicle diameters are smallest and proximity of the great vessels is nearest.

Deep brain stimulation for the treatment of childhood dystonic cerebral palsy

OBJECT Deep brain stimulation (DBS) for dystonic cerebral palsy (CP) has rarely been reported, and its efficacy, though modest when compared with that for primary dystonia, remains unclear, especially in the pediatric population. The authors present a small series of children with dystonic CP who underwent bilateral pallidal DBS, to evaluate the treatments efficacy and safety in the pediatric dystonic CP population. METHODS The authors conducted a retrospective review of patients (under the age of 18 years) with dystonic CP who had undergone DBS of the bilateral globus pallidus internus between 2010 and 2012. Two of the authors independently assessed outcomes using the Barry-Albright Dystonia Scale (BADS) and the Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFMDRS-M). RESULTS Five children were diagnosed with dystonic CP due to insults occurring before the age of 1 year. Mean age at surgery was 11 years (range 8-17 years), and the mean follow-up was 26.6 months (range 2-42 months). The mean target position was 20.6 mm lateral to the midcommissural point. The mean preoperative and postoperative BADS scores were 23.8 ± 4.9 (range 18.5-29.0) and 20.0 ± 5.5 (range 14.5-28.0), respectively, with a mean overall percent improvement of 16.0% (p = 0.14). The mean preoperative and postoperative BFMDRS-M scores were 73.3 ± 26.6 (range 38.5-102.0) and 52.4 ± 21.5 (range 34.0-80.0), respectively, with a mean overall percent improvement of 28.5% (p = 0.10). Those stimulated at least 23 months (4 patients) improved 18.3% (p = 0.14) on the BADS and 30.5% (p = 0.07) on the BFMDRS-M. The percentage improvement per body region yielded conflicting results between rating scales; however, BFMDRS-M scores for speech showed some of the greatest improvements. Two patients required hardware removal (1 complete system, 1 unilateral electrode) within 4 months after implantation because of infections that resolved with antibiotics. CONCLUSIONS All postoperative dystonia rating scale scores improved with pallidal stimulation, and the greatest improvements occurred in those stimulated the longest. The results were modest but comparable to findings in other similar series. Deep brain stimulation remains a viable treatment option for childhood dystonic CP, although young children may have an increased risk of infection. Of particular note, improvements in the BFMDRS-M subscores for speech were comparable to those for other muscle groups, a finding not previously reported.

DURAL SINUS THROMBOSIS ENDOVASCULAR THERAPY

Dural sinus thrombosis is a relatively rare, but potentially devastating disease. The problem occurs when there is extensive thrombosis of the intracranial dural sinuses, the outflow channels of venous blood from the brain. If recanalization does not occur, venous hypertension can lead to cerebral edema, infarction, and hemorrhage. Treatment of this disease usually involves anticoagulants, but with mixed results. Endovascular approaches using direct infusion of thrombolytic drugs into the occluded sinuses may result in excellent recanalization and improved patient outcomes.

Hoffmann sign: clinical correlation of neurological imaging findings in the cervical spine and brain.

Study Design. Retrospective validity study. Objective. To investigate the relationship between Hoffmann sign and radiographical evidence of cervical spinal cord compression and brain lesions. Summary of Background Data. Clinical significance of Hoffmann sign remains controversial with conflicting reports regarding its sensitivity and specificity and its usefulness. Methods. Patients were divided into 2 groups according to the presence of Hoffmann sign on physical examination. Imaging studies were blindly examined by 2 observers for possible cervical and brain lesions. The sensitivity, specificity, positive predictive value, negative predictive value, as well as accuracy for Hoffmann sign as it relates to cervical spinal cord compression and brain pathology, were calculated. Results. Of the 91 patients with a positive Hoffmann sign, 32 (35%) showed severe cervical cord compression and/or myelomalacia. Forty-seven of these patients had brain imaging studies, and 5 (10%) had positive findings. There were 80 patients in the negative Hoffmann sign or control group. Twenty-one (27%) of them had severe cervical cord compression and/or myelomalacia. Twenty-three of these control patients underwent neurological imaging of the brain, and 2 (8%) had positive findings. Hoffmann sign was found to have 59% sensitivity, 49% specificity, 35% positive predictive value, and 72% negative predictive value for cervical cord compression. For brain pathology, sensitivity was 71%, specificity 33%, positive predictive value 10%, and negative predictive value 95%. Conclusion. Hoffmann sign has too low a positive predictive value to be relied upon as a stand-alone physical examination finding and is not a reliable screening tool for solely predicting the presence of cervical spinal cord compression or brain pathology. Level of Evidence: 2

Therapeutic Immunization against Glioblastoma

Glioblastoma is the most common form of brain cancer in adults that produces severe damage to the brain leading to a very poor survival prognosis. The standard of care for glioblastoma is usually surgery, as well as radiotherapy followed by systemic temozolomide chemotherapy, resulting in a median survival time of about 12 to 15 months. Despite these therapeutic efforts, the tumor returns in the vast majority of patients. When relapsing, statistics suggest an imminent death dependent on the size of the tumor, the Karnofsky Performance Status, and the tumor localization. Following the standard of care, the administration of Bevacizumab, inhibiting the growth of the tumor vasculature, is an approved medicinal treatment option approved in the United States, but not in the European Union, as well as the recently approved alternating electric fields (AEFs) generator NovoTTF/Optune. However, it is clear that regardless of the current treatment regimens, glioma patients continue to have dismal prognosis and novel treatments are urgently needed. Here, we describe different approaches of recently developed therapeutic glioma brain cancer vaccines, which stimulate the patient’s immune system to recognize tumor-associated antigens (TAA) on cancer cells, aiming to instruct the immune system to eventually attack and destroy the brain tumor cells, with minimal bystander damage to normal brain cells. These distinct immunotherapies may target particular glioma TAAs which are molecularly defined, but they may also target broad patient-derived tumor antigen preparations intentionally evoking a very broad polyclonal antitumor immune stimulation.

Somatic SMARCB1 Mutation in Sporadic Multiple Meningiomas: Case Report

Background: Multiple intracranial meningiomas account for <10% of all meningiomas. Familial multiple meningiomas have been linked to germline mutations in two genes: neurofibromatosis type 2 (NF2) and SWIch/Sucrose Non-Fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1). Sporadic multiple meningiomas have been associated with somatic NF2 mutations and, to date, there has been no case related to somatic SMARCB1 mutations. Here, we describe the first case. Case Report: A 45-year-old female suffered a head trauma while snowboarding. Subsequent to her injury, she experienced persistent headache, nausea, vomiting, dizziness, and flashing lights in the right eye. Magnetic resonance imaging (MRI) of her brain revealed multiple intracranial meningiomas. She underwent a two-staged craniotomy to remove frontal/parietal/temporal and occipital extra-axial tumors. Pathology confirmed the masses as meningiomas, WHO Grade I. Tumor genetic testing was positive for SMARCB1 mutation but blood genetic testing was negative for SMARCB1 mutation. Conclusion: In sporadic multiple meningiomas, somatic NF2 mutations are usually the suspected genetic alternations. Our case illustrates that somatic SMARCB1 mutation is another genetic risk factor for sporadic multiple meningiomas, albeit rare.

Integrative Medicine as a Vital Component of Patient Care

The landscape of medicine in the United States has been slowly progressing toward a more holistic and individualized approach to healing. Part of this progress has been the integration between western and alternative forms of medicine, a concept that has been described as “integrative medicine.” This approach to healthcare incorporates a patient’s mind, spirituality, and sense of community into the healing process. Integrative medicine has been typically well received and the demand has been steadily increasing in primary US hospitals. Here we cover a number of topics that include the definition of integrative medicine, its potential benefits, current examples of successful implementations, and potential barriers to its expansion. The aim was to give a primary on integrative medicine and its current state for healthcare providers.

Cerebral venous thrombosis: A guide to diagnosis and drug treatment

Cerebral venous thrombosis (CVT) is a relatively rare pathological condition. The clinical presentations can be nonspecific and quite variable, frequently resulting in delayed or missed diagnosis. The symptoms include headache, nausea, vomiting, visual disturbance, altered consciousness and seizures. These symptoms are believed to be caused by increased intracranial pressure secondary to impeded venous drainage.The diagnosis can be made with computed tomography (CT), magnetic resonant imaging (MRI) and cerebral angiography. CT is usually the initial diagnostic test that may show dense clot in the cerebral veins along with hemorrhagic venous infarctions. Empty delta sign can be seen on contrast-enhanced CT. MRI has become the preferred modality for detecting CVT; magnetic resonance angiography (MRA) and venography (MRV) are the best methods for detecting the condition. Angiography, once the standard, is now only indicated when MRI has resulted in an uncertain diagnosis or when endovascular intervention is desired.Therapy should be directed at treating the underlying causative process and symptoms secondary to elevated intracranial pressure. Although there is no consensus regarding antithrombotic treatment, the current trend is to use intravenous heparin initially, followed by warfarin. A newer approach has been developed using interventional endovascular modalities. Local infusion of thrombolytics can be achieved by transvenous catheterisation and catheter navigation. This may offer potential advantages over the established systemic antithrombotic therapy.