Translational Studies on Biologic Fusion of a Vertebral Segment as a Novel Treatment Modality for Low Back Pain.

STUDY DESIGN: Preclinical studies: Efficacy and toxicological studies on lactic acid (LA)-induced sclerozation in pig lumbar discs. Clinical study: Prospective, randomized, double-blinded, placebo-controlled, single ascending dose study investigating the safety and local tolerability of LA. OBJECTIVE: To determine if LA produces sclerozation of the porcine nucleus pulposus (NP) followed by a phase Ib study to evaluate preliminary safety, tolerability, and efficacy of LA in patients with chronic discogenic low back pain. SUMMARY OF BACKGROUND DATA: Surgical stabilization of a motion segment harboring a painful degenerated disc often affords symptomatic relief. In the present study, the hypothesis was tested that LA can produce sclerozation and stabilization of the NP. METHODS: LA (0.2 mL; 60, 120, or 240 mg/mL) or vehicle was injected into the NP or close to the extra spinal region of spinal nerves of young female pigs. The size of the NP, MRI changes, flexural stiffness, and histology of the disc was studied after up to 84 days of survival. Fifteen patients injected intra discally with placebo (iohexol, 1.5 mL, n = 6) or iohexol plus LA (30, 60, or 120 mg/mL; three patients in each group) were followed for up to 12 months. RESULTS: Injection of LA in the pig reproducibly induced sclerozation of the NP and increased flexural rigidity. Histological changes included generation of connective tissue and increased expression of collagen I. No safety concerns were raised. Adverse events in patients were limited to transiently increased low back pain with no obvious difference between treatment groups. There was indication of lower water content of NP injected with the two highest doses of LA. CONCLUSION: LA has a sclerozing effect on the NP in pigs and patients and is therefore a candidate for further clinical studies powered to determine its potential as a treatment of chronic discogenic low back pain. LEVEL OF EVIDENCE: 2.

Hemiplegic (unilateral) cerebral palsy in northern Stockholm: clinical assessment, brain imaging, EEG, epilepsy and aetiologic background factors.

BACKGROUND: The purpose of this study was to describe clinical presentation, epilepsy, EEG, extent and site of the underlying cerebral lesion with special reference towards aetiologic background factors in a population-based group of children with hemiplegic cerebral palsy. METHODS: Forty-seven children of school- age, fulfilling the SPCE (Surveillance of Cerebral palsy in Europe)-criteria of hemiplegic cerebral palsy, identified via the Swedish cerebral palsy register, were invited and asked to participate in the study. RESULTS: Fifteen boys and six girls participated. Of the sixteen children born at term, five had no risk factors for cerebral palsy. Two out of five preterm children presented additional risk factors. Debut of motor impairment was observed in the first year of life in sixteen children. Age at diagnosis varied from 2 months to 6 years. Epilepsy was common and associated with grey- and white matter injury. CONCLUSIONS: Recognizing the importance of risk factors for cerebral palsy, any child with these risk factors should be offered a check-up by a paediatrician or a paediatric neurologist. Thereby reducing diagnostic delay. Epilepsy is common in hemiplegic cerebral palsy and associated with grey- and white matter injury in this cohort.

Magnetic Resonance Imaging of the Vocal Folds in Women With Congenital Adrenal Hyperplasia and Virilized Voices.

PURPOSE: Women with congenital adrenal hyperplasia (CAH) may develop a virilized voice due to late diagnosis or suboptimal suppression of adrenal androgens. Changes in the vocal folds due to virilization have not been studied in vivo. The purpose was to investigate if the thyroarytenoid (TA) muscle is affected by virilization and correlate findings to fundamental frequency (F0). METHOD: A case-control study using magnetic resonance imaging and voice recordings. Four women with CAH with virilized voices (26-40 years), and 5 female and 4 male controls participated. Measurements of cross-sectional TA muscle area, vocal fold length, vocal tract length, and acoustic analyses of F0 were performed. RESULTS: Women with CAH had larger cross-sectional TA muscle area than female control subjects and smaller than male controls. A significant negative correlation was found between TA muscle area and mean F0. The patients had a smaller physiological voice range than both female and male controls. CONCLUSION: Data from our small study suggest that a larger TA muscle area is strongly associated with a lower F0 and thus the anatomical explanation for a female virilized voice, suggesting an androgen effect on the vocal folds. The findings from the present study need to be confirmed in a larger study.

The impact of discography on the surgical decision in patients with chronic low back pain.

BACKGROUND CONTEXT: A reduced frequency of discographies might be the result of increasing concern with long-term effects of discography such as disc degeneration. More knowledge is needed in what patient discography is most likely to influence the surgical decision. PURPOSE: This study was aimed at highlighting how discography affects surgical decisions when performed on one of four different indications in a complicated subgroup of patients with chronic low back pain assumed to be associated with degenerative disc disease (DDD). STUDY DESIGN: Prospective before-after study to analyze how frequently a prediscography preliminary decision was changed and in what direction by adding information from discography in a subgroup of patients with DDD. PATIENT SAMPLE: One hundred thirty-eight patients admitted to a spine clinic more than 4 years with the DDD diagnosis (15% of all) were referred for discography because it was considered that medical history, clinical findings, and magnetic resonance imaging (MRI) were insufficient to make a final assessment on whether to propose surgery/recommend against surgery or what segments to operate on. OUTCOME MEASURES: These were the recorded changes to prediscography preliminary decisions after information was added from discography. METHODS: Before these patients were referred to provocative discography, the surgeon had to select one of four alternative questions/indications being the reason for the discography and choose what decision would have been made if discography would not have been available. The questions/indications were as follows: surgery decided discography to establish whether to treat adjacent segment as well (n=17); several segments degenerated on MRI, pain likely to be discogenic, discography to evaluate what segments to treat (n=56); uncertainty whether pain is discogenic but one suspected segment on MRI (n=38); uncertainty whether pain is discogenic and several segments degenerated in MRI (n=27); the decision after discography was then compared with the prediscography decision and the changes affected by the result of the discography were analyzed. RESULTS: Changes were made to the prediscography decision in 71% of the patients in total. When the surgeon was assured that the pain was discogenic, one segment was added or subtracted in 58% of the patients compared with original prediscography decision. When the surgeon was uncertain if pain was discogenic, the final decision changed from surgery to no surgery in 8%, from no surgery to surgery in 42%, and in cases that were planned for surgery prediscography, one segment was added or subtracted in 17% of the patients. The more certain the surgeon was before discography that the patient's pain was indeed discogenic, the fewer changes between surgical treatment and no surgical treatment took place. The more uncertain the surgeon was before discography that the patient's pain was discogenic, the fewer changes in segments to treat took place in patients who went on to surgery. Changes of involved segments were made to all the 27 patients with a preliminary decision for surgical treatment of the L5-S1 segment solely. The corresponding figure for L4-L5 and L4-L5-S1 was 70% and 53%, respectively. CONCLUSIONS: A high frequency of decisions was altered in this group of surgeons when using discography as an additional examination in patients where uncertainty remains in how to treat after clinical examination, questioning, and MRI.

Magnetic resonance imaging and ultrasound measurements of extraocular muscles in thyroid-associated ophthalmopathy at different stages of the disease.

PURPOSE: To assess extraocular muscle (EOM) involvement in thyroid-associated orbitopathy (TAO) of different stages with magnetic resonance imaging (MRI) and ultrasound techniques. METHODS: A total of 32 patients with TAO were divided into three groups according to whether they had mild active, pronounced active or longstanding inactive disease. Six patients with Graves' disease but no clinical signs of TAO and 10 healthy control subjects were also studied. Muscle volume and cross-sectional area were measured with MRI. A-scan ultrasound was used to measure muscle thickness. RESULTS: The average MRI volume and maximal cross-sectional area of the EOM were significantly larger in patients with pronounced active and longstanding inactive TAO than in control subjects. Increased average muscle thickness measured by ultrasound was found mainly in patients with longstanding disease. Muscle enlargement was seen with MRI and ultrasound in individual patients in all patient groups, including those with Graves' disease but no TAO. Bilateral muscle enlargement was revealed by MRI in about two-thirds of patients with mild active TAO and in all patients with pronounced active and longstanding inactive TAO. Bilateral involvement estimated with ultrasound was less common in all patient groups. The MRI and ultrasound findings were not well correlated in any patient group. CONCLUSIONS: Extraocular muscle enlargement was seen in all patient groups with TAO of differing levels of severity. Measurements with MRI of muscle volume or maximal cross-sectional area are considered good indicators of muscle enlargement in TAO.

Significance of orbital fatty tissue for exophthalmos in thyroid-associated ophthalmopathy.

PURPOSE: To correlate exophthalmos with the volume of extraocular muscle and orbital fatty tissue in thyroid-associated ophthalmopathy (TAO), using MRI that enables the orbital soft tissues to be well defined. METHODS: Thirty-three orbits, 20 from 10 patients with TAO and 13 from 13 controls, were employed. T1-weighted orbital MR slices 2 or 3 mm thick were obtained in axial, coronal and sagittal planes. Tracing the outlines of each structure, we measured the total sectional areas. Volumes of the extraocular muscle, of the fatty tissue and of the bony orbital cavity were calculated by multiplying the slice thickness. Exophthalmos was also measured using axial MRI. RESULTS: In TAO the volume increment of orbital fatty tissue (6.19 cm(3)) was much greater than that of extraocular muscle (1.16 cm(3)). Increase of exophthalmos by 1 mm needed a total orbital volume increment of 0.92 cm(3). The total orbital fatty tissue volume (correlation coefficient 0.70, P=0.06%) and the anterior orbital fatty tissue volume (0.64, P=0.23%) were more closely correlated with the degree of exophthalmos than was extraocular muscle volume (0.58, P=0.8%). Moreover, the volume increment of extraocular muscle and orbital fatty tissue was not always proportional. CONCLUSION: The results show that the orbital fatty tissue involvement is closely related to the degree of exophthalmos. For studying exophthalmos in TAO, the volumetric change, not only in ocular muscles, but also in orbital fatty tissue, should be taken into consideration.