Risk assessment of vascular complications following manual therapy and exercise for the cervical region: diagnostic accuracy of the International Federation of Orthopaedic Manipulative Physical Therapists framework (The Go4Safe project).

QUESTION: What is the diagnostic accuracy of the International Federation of Orthopaedic Manipulative Physical Therapists (IFOMPT) framework to assess the risk of vascular complications in patients seeking physiotherapy care for neck pain and/or headache? DESIGN: Cross-sectional diagnostic accuracy study. PARTICIPANTS: One hundred and fifty patients seeking physiotherapy for neck pain and/or headache in primary care. METHODS: Nineteen physiotherapists performed the index test according to the IFOMPT framework. Patients were classified as having a high, intermediate or low risk of vascular complications, following manual therapy and/or exercise, derived from the estimated risk of the presence of vascular pathology. The reference test was a consensus medical decision reached by a vascular neurologist and an interventional neurologist, with input from a neuroradiologist. The neurologists had access to clinical data and magnetic resonance imaging of the cervical spine, including an angiogram of the cervical arteries. OUTCOME MEASURES: Diagnostic accuracy measures were calculated for 'no contraindication' (ie, the low-risk category) and 'contraindication' (ie, the high-risk and intermediate-risk categories) for manual therapy and/or exercise. Sensitivity, specificity, predictive values, likelihood ratios and the area under the curve were calculated. RESULTS: Manual therapy and/or exercise were contraindicated in 54.7% of the patients. The sensitivity of the IFOMPT framework was low (0.50, 95% CI 0.39 to 0.61) and its specificity was moderate (0.63, 95% CI 0.51 to 0.75). The positive and negative likelihood ratios were weak at 1.36 (95% CI 0.93 to 1.99) and 0.79 (95% CI 0.60 to 1.05), respectively. The area under the curve was poor (0.57, 95% CI 0.49 to 0.65). CONCLUSION: The IFOMPT framework has poor diagnostic accuracy when compared with a reference standard consisting of a consensus medical decision.

[18F]Fluoride PET provides distinct information on disease activity in ankylosing spondylitis as compared to MRI and conventional radiography.

PURPOSE: To relate [18F]fluoride uptake on PET with abnormalities on magnetic resonance imaging (MRI) and conventional radiography (CR) in ankylosing spondylitis (AS) patients. METHODS: Ten clinically active AS patients (female 6/10, age 38 ± 11 years) were included, and both spine and SI-joints were examined. PET scans were dichotomously scored for enhanced [18F]fluoride uptake, MRI scans were scored for fatty lesions, erosions, ankylosis, and bone marrow edema (BME), and CR was scored for erosions, syndesmophytes, and ankylosis. The overlap of lesions across all modalities was evaluated through univariate and multivariate analyses using a generalized mixed model. RESULTS: In the spine, 69 lesions with enhanced [18F]fluoride uptake, 257 MRI lesions, and 88 CR lesions were observed. PET lesions were mostly located in costovertebral and facet joints, outside the field of view (FOV) of the MRI and CR. However, PET lesions inside the FOV of MRI and CR partially showed no abnormality on MRI and CR. In lesions with abnormalities on multiple modalities, both univariate and multivariate analysis showed that PET activity had the strongest association with BME on MRI and ankylosis on CR. In the SI joints, 15 lesions (75%) with PET uptake were found, with 87% showing abnormalities on MRI and CR. CONCLUSION: [18F]fluoride PET lesions are often found outside the scope of MRI and CR, and even in the same location show only partial overlap with abnormalities on MRI (especially BME) and CR (especially ankylosis). This suggests that [18F]fluoride PET partially visualizes aspects of AS separate from MRI and CR, providing novel information. CLINICAL TRIAL REGISTRATION: NL43223.029.13 registered at 02-05-2013.  https://www.toetsingonline.nl/to/ccmo_search.nsf/fABRpop?readform&unids=C1257BA2002CC066C1257B4E0049A65A.

Interexaminer Agreement and Reliability of an Internationally Endorsed Screening Framework for Cervical Vascular Risks Following Manual Therapy and Exercise: The Go4Safe Project.

OBJECTIVE: Clinicians are recommended to use the clinical reasoning framework developed by the International Federation of Orthopaedic Manipulative Physical Therapists (IFOMPT) to provide guidance regarding assessment of the cervical spine and potential for cervical artery dysfunction prior to manual therapy and exercise. However, the interexaminer agreement and reliability of this framework is unknown. This study aimed to estimate the interexaminer agreement and reliability of the IFOMPT framework among physical therapists in primary care. METHODS: Ninety-six patients who consulted a physical therapist for neck pain or headache were included in the study. Each patient was tested independently by 2 physical therapists, from a group of 17 physical therapists (10 pairs) across The Netherlands. Patients and examiners were blinded to the test results. The overall interexaminer agreement, specific agreement per risk category (high-, intermediate-, and low-risk), and interexaminer reliability (weighted κ) were calculated. RESULTS: Overall agreement was 71% (specific agreement in high-risk category = 63%; specific agreement in intermediate-risk category = 38%; specific agreement in low-risk category = 84%). Overall reliability was moderate (weighted κ = 0.39; 95% CI = 0.21-0.57) and varied considerably between pairs of physical therapists (κ = 0.14-1.00). CONCLUSION: The IFOMPT framework showed an insufficient interexaminer agreement and fair interexaminer reliability among physical therapists when screening the increased risks for vascular complications following manual therapy and exercise prior to treatment. IMPACT: The IFOMPT framework contributes to the safety of manual therapy and exercise. It is widely adopted in clinical practice and educational programs, but the measurement properties are unknown. This project describes the agreement and reliability of the IFOMPT framework.

Case report: Candida krusei spondylitis in an immunocompromised patient.

BACKGROUND: Invasive infections with Candida krusei are uncommon and rarely complicated by spondylitis. Previous described cases were solely treated with antimycotic therapy, despite guidelines recommending surgical interventions. CASE PRESENTATION: We describe a case of C. krusei spondylitis in a patient treated with chemotherapy for acute myeloid leukemia. After induction chemotherapy, the patient developed a candidemia, which was treated with micafungin. One month after the candidemia, the patient was admitted with severe lumbar pain. Spondylitis of the L4 and L5 vertebra was diagnosed on MR-imaging, with signs suggesting an atypical infection. The patient was treated with anidulafungin combined with voriconazole. Despite maximal conservative management symptoms gradually worsened eventually requiring surgical intervention. CONCLUSIONS: In contrast to previous case reports, antimycotic treatment alone could be insufficient in treating C. krusei spondylitis.

Bone formation in ankylosing spondylitis during anti-tumour necrosis factor therapy imaged by 18F-fluoride positron emission tomography.

Objectives: Excessive bone formation is an important hallmark of AS. Recently it has been demonstrated that axial bony lesions in AS patients can be visualized using 18F-fluoride PET-CT. The aim of this study was to assess whether 18F-fluoride uptake in clinically active AS patients is related to focal bone formation in spine biopsies and is sensitive to change during anti-TNF treatment. Methods: Twelve anti-TNF-naïve AS patients [female 7/12; age 39 years (SD 11); BASDAI 5.5 ± 1.1] were included. 18 F-fluoride PET-CT scans were performed at baseline and in two patients, biopsies were obtained from PET-positive and PET-negative spine lesions. The remaining 10 patients underwent a second 18F-fluoride PET-CT scan after 12 weeks of anti-TNF treatment. PET scans were scored visually by two blinded expert readers. In addition, 18F-fluoride uptake was quantified using the standardized uptake value corrected for individual integrated whole blood activity concentration (SUVAUC). Clinical response to anti-TNF was defined according to a ⩾ 20% improvement in Assessment of SpondyloArthritis international Society criteria at 24 weeks. Results: At baseline, all patients showed at least one axial PET-positive lesion. Histological analysis of PET-positive lesions in the spine confirmed local osteoid formation. PET-positive lesions were found in the costovertebral joints (43%), facet joints (23%), bridging syndesmophytes (20%) and non-bridging vertebral lesions (14%) and in SI joints (75%). After 12 weeks of anti-TNF treatment, 18F-fluoride uptake in clinical responders decreased significantly in the costovertebral (mean SUVAUC -1.0; P < 0.001) and SI joints (mean SUVAUC -1.2; P = 0.03) in contrast to non-responders. Conclusions: 18F-fluoride PET-CT identified bone formation, confirmed by histology, in the spine and SI joints of AS patients and demonstrated alterations in bone formation during anti-TNF treatment.

Angiogenesis in steno-occlusive vasculopathies as a common pathway for intracranial haemorrhage. A report of six cases.

Vasculopathies, including vasculitis of the central nervous system, can lead to stenosed, cicatrized vessels and the development of arterio-arteriolar collateral vessels. Bleeding due to these vascular changes, although rare, does occur. We describe six patients (all female, age range, 21-52 years; mean age, 42 years) with steno-occlusive lesions of intracranial vessels who presented with an acute intracranial haemorrhage. All had arterial steno-occlusive changes in conjunction with extensive leptomeningeal and arterio-arteriolar collaterals. Within the collaterals, focal dilatations could be identified, which were in close spatial relationship with the intracranial haemorrhage. Cause of bleeding was depicted on CT angiography in four out of six patients. One patient presented in childhood with acute stroke, one patient was diagnosed with Buerger's disease and one with sickle cell disease; the other three patients had no relevant history and the exact cause remained unclear. Outcome was favourable in all patients. Despite focal vascular weaknesses, no recurrent haemorrhage was seen during follow-up, supporting, at least in this small patient group, a conservative wait-and-see policy.

Direct orbital puncture of the cavernous sinus for the treatment of a carotid-cavernous dural AV fistula with a concomitant venous/lymphatic malformation.

A 37- year old male with a long history of a left orbital venous/lympathic malformation presented with ocular injection, increased proptosis and reduced left vision. Angiography demonstrated a carotid cavernous dural AV fistula combined with a concomitant venous/lymphatic malformation. After attempts at transvenous embolization, a direct uncomplicated transorbital puncture of the cavernous sinus via a lateral orbitotomy was performed with complete resolution of ocular symptoms.

Clinical outcome after repeated radiosurgery for brain arteriovenous malformations.

INTRODUCTION: We assessed the clinical and radiological outcome after repeated radiosurgery for brain arteriovenous malformations (bAVMs) after failure of initial radiosurgery. MATERIALS AND METHODS: Fifteen patients underwent repeated radiosurgery. The mean bAVM volume at first radiosurgery (S1) was 4.6 +/- 4.3 ml and that at second radiosurgery (S2) was 2.1 +/- 2.5 ml. The median marginal dose was 18 Gy at S1, and 21 Gy at S2. Modified Rankin Scale (MRS) score was determined in all patients at last follow-up (FU). RESULTS: Complete obliteration was reached in nine patients (60%). Median time to obliteration was 50 months after S2. An excellent outcome (no new neurologic deficiencies, complete obliteration) was reached in seven patients (47%). Eleven patients (73%) showed a MRS1. Radiation-induced complications occurred in 20%, of which 13% occurred after S2. Radiological complications included cyst formation (n = 1), radiation-related edema (n = 4), and radiation necrosis (n = 1), resulting in an increasing mean MRS of 0.5 at S1, 0.6 at S2, to 0.8 at FU. No (re-)bleedings were encountered during 137-patient years at risk. DISCUSSION: Repeated radiosurgery is a viable option for the treatment of small remnant bAVMs. We report 20% permanent radiation-induced complications. Such complications were mainly seen in relatively large, and therefore difficult to treat, bAVMs.

Longitudinal brain volume measurement in multiple sclerosis: rate of brain atrophy is independent of the disease subtype.

BACKGROUND: In multiple sclerosis (MS), brain atrophy depicted by magnetic resonance imaging reflects overall tissue loss, including axonal loss. OBJECTIVE: To determine the course of atrophy by studying the rate of development of brain atrophy in patients who have different subtypes of MS. METHODS: Eighty-three patients with MS (42 with relapsing-remitting, 21 with secondary progressive, and 20 with primary progressive) were studied longitudinally, with an interval of 2 to 4 years. Magnetic resonance imaging included T1- and T2-weighted images to obtain 2 brain volume measurements: (1) the parenchymal fraction as a marker of global brain atrophy and (2) the ventricular fraction as a marker of central atrophy. The annualized rate of global and central brain atrophy was compared between those with different subtypes of MS and related to clinical characteristics, including sex, age, disease duration, and disability. RESULTS: There was a significant decrease of the parenchymal fraction (-0.7% per year; SEM, 0.11% per year) and a significant increase of ventricular fraction (3.7% per year; SEM, 0.54% per year) in the total group. Significant tissue loss was also seen in all 3 subtypes of MS; the decrease in parenchymal fraction was not different between subtypes, whereas the increase in ventricular fraction tended to be larger in patients with secondary progressive MS compared with patients with primary progressive MS. Marginal associations were found between clinical determinants and the rate of brain atrophy. Annualized increase in the ventricular fraction was correlated with age (r = -0.26) and duration of symptoms (r = -0.22): younger patients (mainly patients with relapsing-remitting MS who have a limited disability) displayed a larger increase in ventricular fraction compared with older patients. CONCLUSIONS: The rate of development of brain atrophy is largely independent of the course of the disease and other clinical characteristics. The relentless loss of tissue occurring in MS is not restricted to later (progressive) phases of the disease, thereby stressing the need for early neuroprotective treatment in MS.

Diffuse signal abnormalities in the spinal cord in multiple sclerosis: direct postmortem in situ magnetic resonance imaging correlated with in vitro high-resolution magnetic resonance imaging and histopathology.

In this study, we compared direct postmortem in situ (whole-corpse) sagittal spinal cord magnetic resonance imaging (1.5T) of 7 multiple sclerosis cases with targeted high-resolution in vitro axial magnetic resonance imaging (4.7T) and histopathology. On sagittal in situ magnetic resonance imaging, 1 case had a normal spinal cord, 2 had only focal lesions, 3 had a combination of focal and diffuse abnormalities, and 1 had only diffuse abnormalities. All spinal cords showed abnormalities on high-resolution magnetic resonance imaging and histopathology, confirming the existence of diffuse cord changes as genuine multiple sclerosis-related abnormalities while highlighting the limited resolution of in vivo magnetic resonance imaging.

Differentiation of multiple sclerosis from other inflammatory disorders and cerebrovascular disease: value of spinal MR imaging.

PURPOSE: To determine the value of magnetic resonance (MR) imaging in the spinal cord to differentiate multiple sclerosis (MS) from other inflammatory disorders and cerebrovascular diseases (together, other neurologic disease [OND]). MATERIALS AND METHODS: The study population included 66 patients with OND and 25 patients with MS, who were matched for age, sex, and symptom duration or severity. Brain MR imaging included gadolinium-enhanced T1-weighted and dual-echo T2-weighted spin-echo sequences to assess the number, size, and appearance of lesions, contrast enhancement, and compatibility with diagnostic criteria for MS. Spinal cord MR imaging included cardiac-triggered gadolinium-enhanced sagittal T1-weighted spin-echo and dual-echo T2-weighted sequences to assess the general appearance (normal, focal lesion, diffuse abnormality) and number or size of focal lesions. Images obtained in MS and OND patients were compared. Specificity, sensitivity, accuracy, and positive and negative predictive values with MR images were calculated. RESULTS: Brain images were abnormal in all MS patients and in 65% of OND patients. Abnormal cord images were found in 92% of MS and 6% of OND patients. The combination of brain and spinal cord images increased accuracy of diagnosis compared with use of brain images alone. CONCLUSION: In contrast to MS, cord lesions are very uncommon in OND. This finding can help differentiate these disorders.