Optogenetic surface stimulation of the rat cervical spinal cord.

Electrical intraspinal microstimulation (ISMS) at various sites along the cervical spinal cord permits forelimb muscle activation, elicits complex limb movements and may enhance functional recovery after spinal cord injury. Here, we explore optogenetic spinal stimulation (OSS) as a less invasive and cell type-specific alternative to ISMS. To map forelimb muscle activation by OSS in rats, adeno-associated viruses (AAV) carrying the blue-light sensitive ion channels channelrhodopsin-2 (ChR2) and Chronos were injected into the cervical spinal cord at different depths and volumes. Following an AAV incubation period of several weeks, OSS-induced forelimb muscle activation and movements were assessed at 16 sites along the dorsal surface of the cervical spinal cord. Three distinct movement types were observed. We find that AAV injection volume and depth can be titrated to achieve OSS-based activation of several movements. Optical stimulation of the spinal cord is thus a promising method for dissecting the function of spinal circuitry and targeting therapies following injury. NEW & NOTEWORTHY Optogenetics in the spinal cord can be used both for therapeutic treatments and to uncover basic mechanisms of spinal cord physiology. For the first time, we describe the methodology and outcomes of optogenetic surface stimulation of the rat spinal cord. Specifically, we describe the evoked responses of forelimbs and address the effects of different adeno-associated virus injection paradigms. Additionally, we are the first to report on the limitations of light penetration through the rat spinal cord.

Natural history of rheumatoid arthritis of the cervical spine.

This article reviews the natural history of rheumatoid arthritis involving the cervical spine with special attention given to predictors of paralysis. Understanding the natural history of rheumatoid arthritis of the cervical spine is necessary to determine the benefit of various interventions. The primary treatment goal for cervical instability is prevention of irreversible neurologic injury. The natural history of rheumatoid arthritis for a period of 10 years or more is one of significant disease progression. The natural history of cervical instability in patients with rheumatoid arthritis is more variable, with only some patients having a neurologic deficit develop. Recent studies support prophylactic stabilization of the rheumatoid cervical spine to prevent paralysis in high risk patients. However, proponents for prophylactic arthrodesis must acknowledge that not all cervical instability in rheumatoid arthritis progresses to neurologic deficit, and surgical intervention in patients with rheumatoid arthritis incurs added morbidity and mortality. Identifying the risk factors for progression of cervical instability is the first step in eliminating morbidity and mortality from spinal cord and brain stem compression. Surgical stabilization is indicated not only for those patients with paralysis, but for the subgroups of patients with cervical rheumatoid disease who are at risk for spinal cord and brain stem compression. The posterior atlantodental interval is the most reliable screening tool and predictor of progressive neurologic deficit.

Malignant tumors of the kidney, brain, and soft tissues in children and young adults with the tuberous sclerosis complex.

BACKGROUND: The tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by seizures, mental retardation, and benign tumors of the brain, heart, skin, and kidney. Malignant tumors also can occur in patients with tuberous sclerosis, particularly in the kidney, although they occur less frequently than benign tumors. The types of malignancy that occur in TSC have not been characterized fully. METHODS: Clinical and pathologic features of 8 malignant tumors from 6 TSC patients ranging in age from 22 months to 21 years are reviewed. Six tumors were renal, one was from the inguinal region, and one was from the brain. The tumors were analyzed for loss of heterozygosity (LOH) in the chromosomal regions of the TSC1, TSC2, and VHL genes. RESULTS: Three patients (ages 7, 8, and 20 years) had renal cell carcinomas (RCCs). Two of these patients had multifocal RCCs. All three patients with RCC also had prominent multifocal dysplasia of renal cyst epithelium. Two patients (ages 20 and 21 years) had malignant angiomyolipomas (1 renal and 1 inguinal). One patient (age 22 months) had a Grade 4 giant cell astrocytoma (glioblastoma multiforme). LOH in the region of the TSC2 gene was found, either in the malignant tumor or in benign tumors, in all five patients whose DNA could be analyzed. CONCLUSIONS: Children with TSC, as well as adults with the disease, are at risk for developing malignant tumors. Two types of renal malignancy occur in TSC: RCC, which appears to arise from dysplastic renal cyst epithelial cells, and malignant angiomyolipoma. Tumors cytologically similar to malignant angiomyolipomas also may occur at extrarenal sites. LOH analyses suggest that the majority of patients with TSC who develop malignant tumors have germline TSC2, rather than TSC1, gene mutations.

Management of low back pain. Current assessment and formulation of a blueprint for the health care delivery system of the future.

This article outlines the authors' recommendations for future health care delivery to patients with low back pain and presents one potential blueprint for a modified delivery system. A group of multidisciplinary physicians and support staff that functions as a unified team with common goals is best positioned to overcome the challenges of providing quality care in a managed care environment. The burden on those who manage patients with spine disorders is to define and prove that high quality medical care results in genuine cost savings and better value for the health care customer.

Low back pain and the zygapophysial (facet) joints.

A basic science and clinical review of low back pain due to the lumbar zygapophysial (facet) joints was performed based on a literature search of scientific journals and textbooks. Recent studies estimate that 15% to 40% of chronic low back pain is due to the zygapophysial joints. The histological basis for zygapophysial joint pain has been scientifically established, but the precise clinical etiology remains undetermined. There are no unique identifying features in the history, physical examination, and radiological imaging of patients with pain of lumbar zygapophysial joint origin. Spine physicians diagnose zygapophysial joint pain based on analgesic response to anesthetic injections into the zygapophysial joints or at their nerve supply. Studies on treatment of isolated zygapophysial joint pain are limited. This review summarizes current understanding of lumbar zygapophysial joint disorders while highlighting the need for additional research.

Lumbar zygapophysial (facet) joint injections.

The lumbar zygapophysial joints are a potential cause of back and lower extremity pain. Absolute diagnosis of lumbar zygapophysial joint-mediated pain is based on selective analgesic injections of these joints or their nerve supply. The therapeutic role of zygapophysial joint injections is controversial. This contemporary concepts paper reviews the anatomy, mechanics, pathology, and diagnosis of this condition. A critical review of previous studies assessing the role of diagnostic and potentially therapeutic zygapophysial joint injection procedures is presented. The need for future studies is addressed, and current recommendations for the role of zygapophysial joint injection procedures based on this critical scientific review are provided.

Thoracic zygapophyseal joint pain patterns. A study in normal volunteers.

STUDY DESIGN: Nine asymptomatic volunteers underwent 40 provocative intra-articular injections of the thoracic zygapophyseal joints. OBJECTIVE: The purpose of the study was to isolate and stimulate the thoracic zygapophyseal joints via fluoroscopically guided intra-articular injections to determine whether they are potential pain generators. SUMMARY OF BACKGROUND DATA: Experimentally, the cervical and lumbar zygapophyseal joints have been shown to produce pain, and tentative referral patterns have been established. Referral patterns based on stimulation of the thoracic zygapophyseal joints have not been previously reported. METHODS: Four subjects underwent right-sided T3-T4, T5-T6, T7-T8, and T9-T10 joint injections, and four subjects underwent left-sided T4-T5, T6-T7, T8-T9, and T10-T11 joint injections. One subject underwent both the right- and left-sided joint injections. The zygapophyseal joints were injected with contrast medium only, and the quality, intensity, and distribution of evoked pain was recorded. RESULTS: In this asymptomatic population, 72.5% of joints injected produced a sensation/pain that was different from the sensation of needle advancement through the soft tissues. In 27.5% of joints injected, there was no evoked pain despite adequate capsular distension. Evoked referral patterns were consistent in all subjects. Significant overlap occurred in the referral patterns, with most thoracic regions sharing 3-5 different joint referral zones. CONCLUSIONS: This study provides preliminary confirmation that the thoracic zygapophyseal joints can cause both local and referred pain. A referral pain diagram has been constructed.

Anodal block V anodal stimulation. Fact or fiction.

Anodal block and stimulation are poorly documented electrophysiologic phenomenon. Median and superficial radial nerves are examined in a prospective study to explore the significance of anodal block in routine nerve conduction studies. In addition, the anode's ability to stimulate the peripheral nervous system is evaluated. A monopolar stimulation technique is employed to achieve pure anode-generated responses. Additionally, a similar monopolar cathode stimulation technique is utilized and found to be equivalent to the traditional bipolar cathode stimulation. Based on the findings in this investigation, anodal block does not appear to occur during routine nerve conduction studies; however, transposition of the anode and cathode is clinically significant because the increased distance between the cathode and recording electrode results in predictably prolonged latencies. With higher levels of stimulus intensity, sensory, motor and F wave responses are generated by anodal stimulation in all cases. The actual mechanism of anodal stimulation remains uncertain and requires further study. Predicated on the results of this investigation, it appears that anodal block is an unlikely occurrence during routine electrodiagnostic medicine evaluations.