Identification of Eye-Specific Domains and Their Relation to Callosal Connections in Primary Visual Cortex of Long Evans Rats.

Ocular dominance columns (ODCs) exist in many primates and carnivores, but it is believed that they do not exist in rodents. Using a combination of transneuronal tracing, in situ hybridization for Zif268 and electrophysiological recordings, we show that inputs from both eyes are largely segregated in the binocular region of V1 in Long Evans rats. We also show that, interposed between this binocular region and the lateral border of V1, there lies a strip of cortex that is strongly dominated by the contralateral eye. Finally, we show that callosal connections colocalize primarily with ipsilateral eye domains in the binocular region and with contralateral eye input in the lateral cortical strip, mirroring the relationship between patchy callosal connections and specific sets of ODCs described previously in the cat. Our results suggest that development of cortical modular architecture is more conserved among rodents, carnivores, and primates than previously thought.

Measurement of long-term outcome in patients with cervical spondylotic myelopathy treated surgically.

PURPOSE: The Myelopathy Disability Index and the Neck Disability Index are widely used to assess outcome in cervical spine surgery. Short Form (SF) 36 is a generic measure of health which can be used to measure health gains across a wide variety of conditions. The aim of the current study is to assess long-term outcomes using these measures in a cohort of patients with cervical spondylotic myelopathy (CSM). METHODS: Cohort study with prospective data collection. Patients with CSM being offered decompressive surgery were asked to complete a set of generic and condition-specific outcome measures. This was repeated post-operatively at 3, 12, 24 and 60 months. SF-36 was used as a generic outcome measure and the Myelopathy Index, Neck Disability Score and visual analogue scores for arm, neck and hand pain, paraesthesia and dysthaesia were used as condition-specific outcome measures. RESULTS: Significant improvements in all outcome measures were seen in 70% of the cohort. For SF-36, pre-operative scores were lower than age-matched controls in all domains and significant improvements were seen 3 months following surgery. This improvement in outcome was maintained at 5 years follow-up in approximately two-thirds of those with initial improvement. CONCLUSION: We have used generic and condition-specific outcome measures of health and shown that in patients with CSM treated surgically, up to 70% can expect improvement in their quality of life. These outcome measures are easy to collect and provide objective evidence of changes in quality of life and disability and can help quantify the potential health gains that can be achieved.

Role of retinal input on the development of striate-extrastriate patterns of connections in the rat.

Previous studies have shown that retinal input plays an important role in the development of interhemispheric callosal connections, but little is known about the role retinal input plays on the development of ipsilateral striate-extrastriate connections and the interplay that might exist between developing ipsilateral and callosal pathways. We analyzed the effects of bilateral enucleation performed at different ages on both the distribution of extrastriate projections originating from restricted loci in medial, acallosal striate cortex, and the overall pattern of callosal connections revealed following multiple tracer injections. As in normal rats, striate-extrastriate projections in rats enucleated at birth consisted of multiple, well-defined fields that were largely confined to acallosal regions throughout extrastriate cortex. However, these projections were highly irregular and variable, and they tended to occupy correspondingly anomalous and variable acallosal regions. Moreover, area 17, but not area 18a, was smaller in enucleates compared to controls, resulting in an increase in the divergence of striate projections. Anomalies in patterns of striate-extrastriate projections were not observed in rats enucleated at postnatal day (P)6, although the size of area 17 was still reduced in these rats. These results indicate that the critical period during which the eyes influence the development of striate-extrastriate, but not the size of striate cortex, ends by P6. Finally, enucleation did not change the time course and definition of the initial invasion of axons into gray matter, suggesting that highly variable striate projections patterns do not result from anomalous pruning of exuberant distributions of 17-18a fibers in gray matter.

Prospective study of outcome of foramen magnum decompressions in patients with syrinx and non-syrinx associated Chiari malformations.

OBJECTIVE: To assess the outcome in patients with syrinx and non-syrinx associated Chiari malformations undergoing Foramen Magnum Decompression (FMD). METHODS: Sixty-one patients undergoing FMD for Chiari malformations were prospectively studied with disease specific, generic (SF 36) and subjective (patient reported) outcomes. Of these, 34 patients had objective outcome data including SF36, visual analogue pain scores, Neck and Myelopathy disability indices and the Hospital anxiety and depression score. SF 36 scores were compared to normative data. Data were collected pre-operatively, at 3 months and during long-term follow up (12-60 months). RESULTS: Patient reported improvements in headache and neck pain post-operatively was reported in both syrinx and non-syrinx associated patients. Visual Analogue scores showed improvements in arm pain, paresthesia and hand tingling at 3 months in the syrinx group only. Non-syrinx patients showed significant improvements post-operatively in the Neck disability index and the SF-36 domains for physical function, role physical and bodily pain. Comparison with SF-36 normative data indicates that patients still have significantly impaired quality of life 12 months post-operatively. CONCLUSION: FMD is able to relieve symptoms and improve quality of life in patients with both syrinx and non-syrinx associated Chiari malformations. In syrinx patients we observed symptomatic improvement in limb symptoms as well as radiological resolution of the syrinx. The use of SF-36 allows the health gain associated with FMD to be quantified. SF 36 is not adequate as a stand alone measure of outcome in this complex disorder and we advocate the concurrent use of disease specific measures and post-operative imaging of the syrinx.

The surgical management of metastatic spinal disease: prospective assessment and long-term follow-up.

The last decade has witnessed a resurgence of interest in the surgical treatment of metastatic spinal disease to compliment radiotherapy. A recent randomized controlled trial looking directly at this issue concluded strongly in favour of a combination of surgical decompression and radiotherapy, and there is now growing enthusiasm for surgery to play a role in the management of these patients. We present a prospective cohort study of 62 patients who presented with metastatic cord or cauda equina compression, and were treated with surgical decompression and fixation where necessary. Patients were treated by one surgeon working in a single unit. They were followed-up long term and were assessed objectively, by clinical assessment and prospective questionnaires that included SF36, visual analogue pain scores and Roland Morris back pain scores. Sixty-two patients with a median age of 62 (22-79 years, 27 male) were included in the study. The commonest primary tumours were breast (26%) and lymphoma (13%). The majority of patients had involvement of thoracic vertebrae (58%). 56% of patients were alive at 1 year and 28% at 3 years, with significant improvements observed in both walking and continence. Similarly, significant improvements were seen in SF36 quality of life scores as well as pain. With careful patient selection, long-term survival and good quality of life can be achieved. However, not every patient is suitable or appropriate for surgery, and the discussion focuses on where the surgical threshold should be set.

Prospective study of outcomes in lumbar discectomy.

Establishing standardized methods to assess outcome is needed to measure the effectiveness of surgery in relieving symptoms and improving quality of life. We prospectively studied 203 patients undergoing primary lumbar discectomy. Data was collected before surgery, at 3 months postoperatively and at long-term follow-up (12-60 months, median 24) using both disease-specific (visual analogue scores, Roland-Morris disability scales, and Hospital Anxiety and Depression scales) and generic (SF-36) instruments. Continued significant symptomatic benefit was observed to long-term assessment and the health gains in this patient group compared favourably with other elective surgical procedures. We have used this data to validate the SF-36 for use in this context and we recommend that SF36 should be used as a sole measure of outcome in routine practice, as well as in future studies.

High-dose radiotherapy in the management of chordoma and chondrosarcoma of the skull base and cervical spine: Part 1--Clinical outcomes.

AIMS: Patients with chordoma and chondrosarcoma in the skull base present a complex multidisciplinary problem. These tumours are rare and occur in difficult anatomical regions. We reviewed the local control and survival of patients treated in our centre. MATERIALS AND METHODS: Between 1996 and 2005, 12 adult cases of chordoma (nine) and chondrosarcoma (three) in the skull base or cervical spine were treated in our centre. The median follow-up is currently 38 months. One patient was treated with palliative intent. In 10 cases the prescription dose was 65 Gy in 39 fractions. The target volumes were measured, and the target maximum and minimum doses and the equivalent uniform dose (EUD) for the phase I plans were recorded. RESULTS: Local control was achieved in 11 of 12 cases. One chordoma patient failed locally, and one other died of metastatic disease despite local control. The 3- and 5-year cause-specific survival for the series was 88 and 75%, respectively. The mean phase I planning target volume (PTV) was 120.4 cm(3). The median minimum dose in the phase I PTV was 81.0%. The median EUD (expressed as a percentage of the prescribed dose) for the phase I PTV, calculated using a value for the exponent a of -15, was 98.3%. The phase I EUD was below 80% in two of the 12 cases. CONCLUSIONS: Our results confirm a need for aggressive local surgery and high-dose radiotherapy, and endorse multidisciplinary working. Although charged particle therapy is accepted as providing optimal treatment plans, in eight of our patients travel abroad would not have been feasible. This series provides encouraging results for carefully planned photon conformal radiotherapy, carried out in close collaboration with a specialist surgical team.

Laminectomy for lumbar canal stenosis: a safe and effective treatment.

Lumbar canal stenosis (LCS) is a common condition affecting elderly patients for which a significant number undergo surgery. The validity and safety of simple laminectomy in this condition is not fully understood. Furthermore, the presence of pre-existing spondylolisthesis is controversial with respect to the need for additional spinal stabilization. We prospectively studied a consecutive cohort of 100 patients with clinical and radiological LCS under the care of a single spinal surgeon. Outcome measures (SF-36, visual analogue scores for back and leg symptoms, and the Roland/Morris back pain scores) were assessed preoperatively, 3 months postsurgery and at long-term (median 2 years) follow-up. We have shown a significant improvement in outcome sustained in the long-term with minimal morbidity. Patients with pre-existing spondylolisthesis accounted for 23% of the cohort and, having received identical treatment, showed no significant difference in outcome compared with patients with normal alignment.

Primary central nervous system lymphoma: a single-centre experience of 55 unselected cases.

AIMS: Current treatment for primary central nervous system lymphoma (PCNSL) involves high-dose methotrexate (HDMTX) with or without radiotherapy. Many published studies describing this approach include a highly selected group of patients. We report a single-centre experience of unselected cases of PCNSL. MATERIALS AND METHODS: We retrospectively reviewed the case notes of 55 consecutive patients diagnosed with biopsy-proven PCNSL between 1995 and 2003 at Addenbrooke's Hospital Cambridge, UK. We describe the treatment and outcome, including survival, treatment-related toxicity and long-term functional disability. RESULTS: At diagnosis, 45% of patients were considered unfit to receive treatment with HDMTX, owing to poor performance status or comorbidity. These patients had a median survival of 46 days and may not have been included in other published studies. The remaining patients were treated with a chemotherapy regimen, which included HDMTX. Patients who received at least one cycle of a chemotherapy containing HDMTX had a median survival of 31 months. Forty per cent did not complete planned chemotherapy owing to toxicity, disease progression or death. The median survival of patients treated with HDMTX aged 60 years compared with patients aged under 60 years was 26 months vs 41 months (P = 0.07), respectively. Younger patients treated with HDMTX, who achieved complete remission with chemotherapy, had a median survival of 56 months. We identified a high incidence of functional disability among survivors, resulting from a combination of the tumour itself, the neurosurgical procedure required for diagnosis and the late neurotoxicity of combined chemoradiotherapy. CONCLUSION: The treatment of PCNSL is associated with significant early and late toxicity. Further attempts to improve treatment should address mechanisms to reduce this toxicity. In particular, the benefit of radiotherapy in patients who achieve complete remission with HDMTX will remain uncertain until it is addressed in a multicentre, randomised trial.

Loss of inter-vertebral disc height after anterior cervical discectomy.

Most surgeons undertaking anterior cervical discectomy (ACD) introduce a bone graft or cage into the disc space when the decompression is complete. This is done to prevent segmental collapse, preserve cervical spine alignment and to promote fusion. We have conducted a prospective observational cohort study to investigate the relationship between loss of disc height, cervical spine alignment and clinical outcome in 140 patients undergoing ACD without inter-body graft or cage. At a minimum of 12 months after operation changes in disc space height and cervical spine alignment were correlated with clinical outcome measured by SF36, Neck Disability Index, and visual analogue neck and arm pain scores. There was no relationship between loss of disc height and outcome. Loss of the overall cervical lordosis was present in 71 patients and segmental kyphosis was found in 69. Analysis of clinical outcome showed no significant differences between patients with preserved and abnormal cervical alignment. Neither loss of disc height nor disturbance of cervical alignment compromised clinical outcome in the first year following ACD.

Conformal rotation therapy with central axis beam block is a feasible alternative to intensity-modulated radiotherapy for chordomas of the cervical spine.

AIMS: Paraspinal tumours, such as chordoma, represent a treatment challenge for oncologists, requiring high dose to the target volume without exceeding the tolerance dose of the spinal cord. Intensity-modulated radiotherapy (IMRT) is helpful in achieving sharp dose gradients and conformation of dose to the target volume. We present a simpler technique--conformal rotation therapy with a central axis beam block (CRT + BB), which can provide similar dose distributions. MATERIALS AND METHODS: A patient with a cervical chordoma developed postoperative recurrence and was treated with high-dose palliative radiotherapy. Treatment was delivered using CRT + BB, with three fixed beams and three coplanar arcs. A dose of 62 Gy in 31 fractions was delivered to the 100% isodose, giving a maximum spinal cord dose of 49.6 Gy. The patient relapsed 2 years later, and was re-treated using the same technique to a dose of 57 Gy in 30 fractions. Estimates of spinal cord repair rates in primates were used to determine the tolerance dose of the spinal cord for re-treatment. The patient remained well for a further 25 months before developing local recurrence, which was treated with palliative chemotherapy. RESULTS: Re-treatment plans using CRT + BB and IMRT were compared. Dose-volume histograms show equivalence of dose to the spinal cord, although the IMRT plan delivered a slightly higher dose to tumour and lower dose to surrounding soft tissues. CONCLUSION: Treatment using CRT + BB requires careful planning and discussion with neurosurgeons before surgery. The normal curvature of the cervical spine must be eliminated if possible, and the patient must be immobilised with the neck horizontal. If these geometric constraints can be satisfied, then CRT + BB can be used as a safe and effective alternative treatment to IMRT for tumours at this site.

Assessment of fusion after anterior cervical discectomy.

There is no established method to assess fusion in patients following anterior cervical discectomy. In this study we have made a series of measurements to detect movement between vertebrae adjacent to an operated space. The absence of movement implies structural union between adjacent vertebrae. Measurements have been made in two distinct surgical groups. Group A patients had anterior cervical discectomy with insertion of a BOP graft into the disc space. Group B patients underwent simple anterior cervical discectomy with no spacer or graft material inserted, the disc space being left empty. Details of the measurements and interpretation of results are described. In the absence of a 'gold standard' to assess bony union we propose that these measurement methods provide an objective and scientific method to assess fusion at the operated level after anterior cervical discectomy. Objective measurement of fusion will allow comparison between different surgical techniques that claim fusion as an end point. It will also become possible to study the influence of fusion on clinical outcome in different surgical populations.

Measurement of outcome in patients with cervical spondylotic myelopathy treated surgically.

The objective was to establish the role of the Short Form 36 (SF 36) as an objective measure of clinical outcome in cervical spondylotic myelopathy (CSM), and took the form of a prospective observational study. Seventy patients with symptomatic CSM were treated by surgical decompression. Health status was measured pre- and 3 months postoperation using objective, validated patient completed measures. These were the SF 36, neck disability index, myelopathy disability index and analogue scores for neck pain and arm symptoms. SF 36 scores were compared with age matched control data. Twelve-month postoperative data are available in a proportion of the cohort. CSM patients have lower preoperative SF 36 scores than age-matched population controls. Comparing pre- and postoperative SF36 scores for the physical functioning domain 64% of patients improve, 23% show no change and 14% of patients continue to deteriorate (Wilcoxon P< 0.0001). These changes are replicated in other domains of the SF36 and by the other measures of outcome. The SF36 is responsive, valid, and practical. Its use for determining outcome in the surgical treatment of CSM is recommended.

Prospective study of clinical and radiological outcome after anterior cervical discectomy.

Most surgeons undertaking anterior cervical discectomy (ACD) introduce a bone graft or cage into the disc space when the decompression is complete to prevent segmental collapse and preserve cervical spine alignment. We have conducted a prospective observational cohort study to investigate the relationship between cervical spine alignment and clinical outcome in 55 patients undergoing ACD without interbody graft or cage. At 12 months, the overall alignment of the cervical spine and the presence of segmental kyphosis at the operated level were correlated with clinical outcome measured by SF 36, Neck Disability Index and visual analogue neck pain score. Loss of the overall cervical lordosis was present in 30 patients and segmental kyphosis was found in 18. Analysis of clinical outcome showed no statistical differences between patients with preserved and abnormal cervical and segmental alignment. Disturbance of cervical and segmental alignment is common in patients following cervical discectomy, but does not appear to compromise clinical outcome at 12 months.

Assessing outcome in lumbar disc surgery using patient completed measures.

Measuring outcome after spinal surgery is difficult. The objective of this study was to assess the use of four measures in establishing outcome in patients undergoing lumbar discectomy. Forty-six consecutive patients who had undergone two operations for lumbar disc prolapse and 54 patients who had undergone one operation for the same condition over the same period were identified. The SF-36 questionnaire was used to assess general health. The Roland-Morris questionnaire and a simple modification of the Roland-Morris questionnaire were used to assess back and leg related disability, respectively. Analogue pain scales were used to measure back pain and sciatica. The SF-36 scores revealed significantly worse health status in the two operation compared with the one operation patients and in all patients compared with the normal population. Using the Roland-Morris and the leg disability questionnaires, patients who had undergone two operations reported significantly worse disability (Roland-Morris, 53%, poor outcome) than those who had undergone one operation (Roland-Morris, 19%, poor outcome). There was significantly greater back disability than leg disability in both groups of patients and this was confirmed by the analogue pain scales. In patients who had undergone two operations, 25% classified their back pain as very bad or unbearable, and 22.5% described very bad or unbearable leg pain. For the one operation patients these figures were 9.5 and 2.4%, respectively. The results demonstrate that both generic and condition specific patient completed measures have the potential to detect differences in outcome between patients who have undergone either one or two lumbar disc operations. The study provides support for the use of these patient completed measures in assessing outcome in lumbar disc surgery.

Imaging of compressive vertebral haemangiomas.

Compressive vertebral haemangiomas (VHs) are rare. Correct preoperative diagnosis is useful both for operative planning (since compressive VHs are extremely vascular lesions) and to allow preoperative embolisation. Numerous radiological signs for VHs have been described, but compressive VHs frequently have atypical features. In particular, magnetic resonance features are not well established. We present imaging features in three cases of compressive VH and review the imaging findings in an additional 106 previously published cases. Findings were typical in 52 of 80 plain film (65%), 33 of 41 computed tomography (80%) and 13 of 25 magnetic resonance examinations (52%). The prevalence of previously described imaging features is reported. Awareness of the range of magnetic resonance features is important since this is frequently the initial investigation in patients presenting with symptoms of neural compression. Since computed tomography is typical in 80% of cases, this is a useful confirmatory test if magnetic resonance features are suspicious but not diagnostic of compressive VH.

A study of perioperative lumbar cerebrospinal fluid pressure in patients undergoing acoustic neuroma surgery.

The objective of this study was to measure changes in cerebrospinal fluid (CSF) pressure and cerebrovascular hemodynamics following acoustic neuroma surgery. The subjects were 32 patients undergoing translabyrinthine or retrosigmoid excision of acoustic neuroma. CSF pressure and the amplitude of the CSF pressure pulse wave were measured using lumbar catheters, and all variables were recorded minute by minute on a microcomputer. Transcranial doppler (TCD) was used to measure flow velocity in the middle cerebral artery in 10 patients to monitor changes in cerebral hemodynamics. In the 24 hours after surgery, all patients showed a statistically significant rise in CSF pressure from 11.4 mm Hg (standard deviation [SD] 6.1) to 19.6 mm Hg (SD 5.2) and a corresponding fall in the compliance of the CSF compartment. These changes were reversed within 48 hours, and the CSF pressure fell below the preoperative level over the next 4 days without any drainage of CSF. The results of this study demonstrate a transient increase in CSF pressure and decrease in craniospinal compliance that is provoked by surgery. The most plausible explanation for this disturbance is impaired CSF absorption, which resolves rapidly in most patients without therapeutic CSF drainage.

The 'Folic Acid Campaign': has the message got through? A questionnaire study.

There is now clear evidence that folic acid reduces the risk of neural tube defects. In February 1996 the Health Education Authority launched a publicity campaign to inform women of the benefits of periconceptual folic acid. We have surveyed 1000 women to assess the compliance of pregnant women with the Department of Health's recommendations about taking folic acid. Of the women, 761 (76%) said they knew about the benefits of folic acid but only 433 (43%) of them took it before pregnancy. Of the 567 women who did not take folic acid before conception, 227 had not planned their pregnancy and 239 did not know about the benefits. Of the 644 women who planned their pregnancy and knew about the benefits of folic acid before conception 211 still did not take folic acid pre-pregnancy. These findings have important implications for public policy and health professionals if the incidence of neural tube defect is to be reduced further.