Choroidal structural evaluation in inactive Graves’ ophthalmopathy

PurposeTo investigate the changes in the choroidal structure in patients with inactive Graves Ophthalmopathy (GO).DesignA prospective, masked, observational cross-sectional study.MethodsChanges in choroidal vascularity index (CVI) were studied in the patients with inactive GO using binarization on enhanced depth imaging optical coherence tomography (EDI-OCT) images. Choroidal area, subfoveal choroidal thickness (SFCT), stromal area, luminal area, CVI and retinal nerve fiber layer (RNFL) thickness was used to compare the eyes of sixty-four age-, gender-matched healthy subjects. All measurements were done separately both subfoveal (1500 µm) and total choroidal area (7500 µm). The relation between CVI or SFCT and age, gender, duration of disease, the severity of disease, TRAb (thyrotropin receptor autoantibody), smoking status, and exophthalmometer readings were evaluated.ResultsThere were 56 patients (30 female, 26 male; mean age: 39.5 ± 11.4 years) in the GO group and 64 patients (34 female, 30 male; mean age: 42.2 ± 5.6 years) in the healthy subject group. There was no statistically significant difference between subjects with GO and healthy controls regarding age (p = 0.24) and gender distribution (p = 0.55). Patients with GO had significantly higher intraocular pressure (p = 0.001) and exophthalmometer readings (p = 0.0001) than the healthy controls. The SFCT, CVI₁₅₀₀ and the stromal area1500 was significantly different between the groups (p = 0.009, p = 0.009, p = 0.011, respectively). Multivariate analysis showed that age (-0.871, p = 0.02) was highly correlated with the decreased SFCT, and duration of disease (0.524, p = 0.001) was significantly positively correlated with SFCT. Luminal area1500 (-0.416, p = 0.0001)and stromal area1500 (-0.657, p = 0.0001) were significantly negatively correlated with CVI₁₅₀₀ in the patients with GO.ConclusionAlthough higher CVI₁₅₀₀ was observed in GO patients than in healthy controls, the degree of increase was not the same in the CVI₇₅₀₀. Age and duration of disease significantly affect the SFCT, and luminal area₁₅₀₀ and stromal area₁₅₀₀ significantly affect the CVI₁₅₀₀.     

Exclusion of brain lesions: is MR contrast medium required after a negative fluid-attenuated inversion recovery sequence?

We hypothesized that in patients with negative fluid-attenuated inversion recovery (FLAIR) images T(2) weighted fast spin-echo (FSE) images and T(1) weighted spin-echo (SE) images before and after intravenous administration of gadolinium-based contrast medium display no pathology either. Thus, we assessed the negative predictive value of FLAIR images to rule out MR-detectable brain lesions. 1026 consecutive cranial MR examinations were reviewed. Routine MRI of the brain included T(1) weighted coronal imaging before and after administration of gadopentetate dimeglumine, axial T(2) weighted FSE and fast-FLAIR imaging. The FLAIR images were rated by two radiologists into categories of 0 (without pathologic changes) and 1 (with pathologic changes). Two other radiologists analysed the complete examination. In 284 MR examinations of the brain no abnormalities were found (28%). FLAIR-ratings were false-negative in four cases and false-positive in 30 cases. Sensitivity and specificity of the FLAIR sequence for MR-detectable brain lesions were 99.5% and 89.4%. The unselective application of gadolinium avoided one false-negative MR-reading and improved the sensitivity of the MR-examination from 99.5% to 99.6%. Positive and negative predictive values were 96.1% and 98.4%, respectively. The interobserver reliability was kappa=0.93 for the FLAIR-readers and 0.89 for the readers who rated the complete examination. In conclusion, negative FLAIR images provide a high negative predictive value for MR-detectable brain lesions. Thus, in patients with negative FLAIR images the unselective application of gadolinium seems to be unnecessary.     

Evaluations of non-contrast enhanced MR venography with inflow inversion recovery sequence in diagnosing Budd–Chiari syndrome

Non-contrast-enhanced (NCE) inflow inversion recovery magnetic resonance venography (MRV)and digital subtraction angiography (DSA) examination were carried out in 35 patients who were suspected of having Budd–Chiari syndrome (BCS). With DSA as the reference, NCE MRV got 100% in the diagnostic sensitivity, 67.8% in the specificity, 97.1% in the accuracy, 100% in the negative predictive value, and 96.9% in the positive predictive value. The consistency between NCE MRV and DSA in the depiction of IVC was excellent. NCE MRV is regarded as an alternative method in the diagnosis of BCS.     

Incidence of radiation-induced Graves’ disease in patients treated with radioiodine for thyroid autonomy before and after introduction of a high-sensitivity TSH receptor antibody assay

Autoimmune hyperthyroidism may occur several months after radioiodine therapy (RIT) for functional thyroid autonomy. Exacerbation of pre-existing subclinical Graves disease (GD) has been held responsible for this phenomenon. Determination of TSH receptor antibody using solubilised porcine epithelial cell membranes is insensitive and may have failed to diagnose GD in these patients before RIT. Following the introduction of a more sensitive assay, using the human TSH receptor as an antigen, it has been expected that the incidence of radiation-induced GD after RIT for functional thyroid autonomy will be reduced. In a first group of 1,428 patients treated between November 1993 and March 1997 (group I) we used the porcine TRAb assay to exclude GD, while in a second group comprising 1,408 patients treated between January 2000 and December 2001 (group II), GD was excluded using the human TRAb assay. A matched control group of 231 patients was derived from group II. In group I a total of 15 (1.05%) patients developed obvious or suspected radiation-induced GD, while in group II 17 (1.2%) did so; the interval until development of GD was 8.4 and 8.8 months, respectively, after RIT. Serum anti-thyroid peroxidase levels before RIT were elevated in 36.4% of group I patients and 47.1% of group II patients, but in only 5.6% of the control group. Other non-specific signs of mild immunopathy of the thyroid were seen retrospectively in 73.3%, 64.7% and 16.0% of the patients in these three groups, respectively. In conclusion, the introduction of a high-sensitivity TRAb assay did not reduce the incidence of autoimmune hyperthyroidism occurring late after RIT for functional thyroid autonomy, but mild immunopathy of the thyroid is seen more frequently in these patients and seems to be a predisposing factor in the development of radiation-induced GD.     

Out of balance – Postural control in cancer patients before and after neurotoxic chemotherapy

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect deriving from neurotoxic chemotherapeutic agents. The underlying nerve injury can affect proprioception causing impaired postural control, gait difficulties and a higher risk of falling. Overall, the symptoms and functional limitations negatively affect patients’ independence and quality of life.Research questionOur objective was to analyze postural control in cancer patients before and after neurotoxic chemotherapy and to compare these data to healthy controls.MethodsParticipants were 35 cancer patients (PAT) and 35 healthy, one-to-one gender, age, height, and weight matched controls (HMC). Postural control of HMC was tested once, whereas PAT were tested prior to (PAT_pre) and three weeks after completion of neurotoxic chemotherapy (PAT_post). Temporal, spatial and frequency domain measures of the center of pressure (COP) were calculated using a force plate. The following balance conditions were analyzed: bipedal stance with open (BP_EO) and closed eyes (BP_EC), semi-tandem (ST_EO, ST_EC) and monopedal stance (MP_EO). CIPN was assessed clinically (Total Neuropathy Score) and via questionnaire. Time and group differences were determined by using Wilcoxon-signed-rank tests. Spearman correlation was applied to analyze associations between severity of CIPN and postural control.ResultsPAT_post showed significantly increased temporal and spatial measures of the COP (p < .05) – both after neurotoxic chemotherapy (PAT_pre–PAT_post) and in comparison to HMC. Withdrawal of visual control resulted in greater temporal and spatial COP displacements in PAT_post than in the comparative groups (PAT_pre, HMC). Correlation analyzes revealed moderate associations of COP measures with clinical CIPN measures and low to none for the questionnaires.SignificanceThree weeks after completion of neurotoxic chemotherapy, PAT_post showed significant balance deficits compared to PAT_pre and HMC. Especially the deficits in the standing conditions with closed eyes may indicate an impaired proprioception. This hypothesis is supported by the finding that stronger CIPN symptoms were associated with poorer postural control. However, future studies need to take further influencing factors on postural control into account (e.g. strength) in order to generate efficacious rehabilitation measures.     

Role of imaging methods in diagnosis and treatment of Morton’s neuroma

Among the many causes of forefoot pain, Morton’s neuroma (MN) is often suspected, particularly in women, due to its high incidence. However, there remain controversies about its relationship with symptomatology and which diagnostic and treatment choices to choose. This article mainly focuses on the role of the various imaging methods and their abilities to support an accurate diagnosis of MN, ruling out other causes of forefoot pain, and as a way of providing targeted imaging-guided therapy for patients with MN.     

What is to be gained by imaging the same animal before and after treatment?

Experimental design includes decisions to perform measurements with intact animals or truncated in vivo measurements followed by dissection and ex vivo measurements. The design may be driven by advantages and disadvantages of the choices. Analytical results are presented here that can provide a basis for certain experimental design choices. Design considerations include longitudinal studies in the single animal that bracket a treatment, joint observations by supplementing the imaging data with plasma and/or ex vivo sampling after dissection, multiple injections of increasing molar base or administration of a molar dose that results in the occupation of a significant fraction of the target receptors. Of particular interest when constructing an experimental design is the reduction of bias. Analysis tools for this purpose include reparameterization and model application without the formation of time-based averaging.     

A prospective comparison study of fast T1 weighted fluid attenuation inversion recovery and T1 weighted turbo spin echo sequence at 3?T in degenerative disease of the cervical spine

Objective:

This study compared T₁ fluid attenuation inversion recovery (FLAIR) and T₁ turbo spin echo (TSE) sequences for evaluation of cervical spine degenerative disease at 3 T.

Methods:

72 patients (44 males and 28 females; mean age of 39 years; age range, 27–75 years) with suspected cervical spine degenerative disease were prospectively evaluated. Sagittal images of the spine were obtained using T₁ FLAIR and T₁ TSE sequences. Two experienced neuroradiologists compared the sequences qualitatively and quantitatively.

Results:

On qualitative evaluation, cerebrospinal fluid (CSF) nulling and contrast at cord–CSF, disc–CSF and disc–cord interfaces were significantly higher on fast T₁ FLAIR images than on T₁ TSE images (p < 0.001). No significant difference was seen between the sequences in evaluation of neural foramina and bone–disc interface. On quantitative evaluation, the signal-to-noise ratios of cord and CSF on fast T₁ FLAIR images were significantly higher than those on T₁ TSE images (p < 0.05). Contrast-to-noise ratios (CNRs) of cord to CSF on T₁ FLAIR images were significantly higher than those of T₁ TSE images (p < 0.05). CNRs of bone to disc for T₁ weighted TSE images were significantly higher than those of T₁ FLAIR images (p < 0.05).

Conclusion:

At 3 T, T₁ FLAIR imaging is superior to T₁ TSE for evaluating cervical spine degenerative disease, owing to higher cord–CSF, disc–cord and disc–CSF contrast. However, intrinsic cord contrast is low on T₁ FLAIR images.

Advances in knowledge:

T₁ FLAIR is more promising and sensitive than T₁ TSE for evaluation of degenerative spondyloarthropathy and may provide a foundation for development of MR protocols for early detection of degenerative and neoplastic diseases.T₁ weighted turbo spin echo (TSE) sequence is a routine sequence included in our protocol to image the cervical spine at 3 T. Prolongation of tissue spin lattice relaxation times at 3 T relative to those at 1.5 T results in reduced contrast between the spinal cord and cerebrospinal fluid (CSF) on T₁ weighted TSE (T₁ TSE) images.^1–3 To overcome this problem, T₁ weighted fluid attenuated inversion recovery (T₁ FLAIR) sequences are frequently used for imaging the spine.^1,4 Inversion recovery sequences provide increased tissue contrast vis-à-vis spin echo sequences. These were initially developed for examination of the spine at 1.5 T⁴ and were designed to null the signal from CSF and maximize contrast between different pairs of tissues, which are commonly seen on spine images as well as between tissue and CSF. Typical combinations of T₁ FLAIR sequence of repetition time (TR), inversion time (TI) and echo time (TE) at 1.5 T are 2000, 862 and 10 ms⁴ and 2000, 862 and 6 ms⁵ and at a lower field strength (0.2 T) 970, 450 and 29 ms, respectively.⁶ For operation at 3 T, longer values of TR, TI and TE are generally employed, e.g. 2675, 2000 and 17 ms.¹ Longer TRs are acceptable for the T₁ FLAIR sequence at 3 T, and, by mathematical simulation, Oda et al⁷ showed a wide but optimum range of TRs between 2400 and 3900 ms at 3 T. Although T₁ FLAIR sequences are commonly used in the spine and are said to provide excellent delineation of CSF, bone and disc bone interfaces at 3 T,^1–3 to date there has been little critical evaluation of their performance. Most of the articles have dealt with the role of T₁ FLAIR sequence in imaging degenerative disease of the lumbar spine,^5,8 wherein suppression of the abundant quantity of CSF within the lumbar thecal sac would allow for greater tissue contrast and improved image quality. On the contrary, the relative paucity of the sleeves of CSF surrounding the cervical cord would seem to present a relative hindrance in the assessment of the cervical spine using the T₁ FLAIR sequence. In this article, we describe a prospective comparison of T₁ FLAIR and T₁ TSE sequences for evaluation of cervical spine degenerative disease at this field strength.     

Failure of radioiodine treatment in Graves’ disease intentionally caused by a patient: Suspected Munchausen syndrome

We experienced a case with Graves' disease in which radioiodine treatment failed probably because of intentional spitting out of capsules of radioactive iodide. Chemical analysis of the substances collected from the trash in the treatment room demonstrated that its profile was the same as that of the capsules for radioiodine administration. Measurement of the iodine concentrations in a blood sample obtained at 24 h after the administration of radioiodine indicated that the patient showed iodine excess. These findings suggest that this may be a case of Munchausen syndrome.     

Change in the intrathyroidal kinetics of radioiodine under continued and discontinued antithyroid medication in Graves’ disease

Purpose This study evaluated the thyroidal kinetics of radioiodine in Graves’ disease under continued thiamazole medication and after discontinuation of thiamazole for 1–2 days, with a view to keeping the period of discontinuation as short as possible and to exploring the underlying mechanism of a postulated radioprotective effect of antithyroid drugs. Methods In 316 patients, diagnostic and therapeutic radioiodine kinetics were followed up for 2 days by ten uptake measurements each and were defined mathematically by a two-compartment model. Results Without thiamazole or when thiamazole was discontinued for at least 2 days, all uptake curves could be fitted perfectly by a simple in- and output function; the mean square error (mse) was 0.38 (test) and 0.28 (therapy). Under continued thiamazole medication (11.0±7.0 mg/day), the energy dose delivered to the thyroid was lowered by factor of 2.5. Uptake curves were deformed (mse: 1.06, test and 0.86, therapy) and appeared two peaked, suggesting coexistence of follicles with blocked and follicles with intact hormone synthesis and hence heterogeneous radioiodine uptake in the thyroid. In patients with maximally altered uptake curves, the success rate was as low as 31%. One day after discontinuation of thiamazole, mse was still increased (0.78, test), while 2 days afterwards it had normalised (0.36, test) and 3 days afterwards (mse: 0.24, therapy) the success rate was 87%. Conclusion Efficacy of radioiodine therapy under continued thiamazole medication is reduced not only by a lower uptake and shorter half-life of radioiodine, but also by a heterogeneous energy dose distribution in the thyroid. Discontinuation of thiamazole (but probably not of propylthiouracil) for at least 2 days is required to restore the efficacy of radioiodine.     

Three basic patterns of changes in serum thyroid hormone levels in Graves’ disease during the one-year period after radioiodine therapy

The purpose of this study was to clarify the characteristic patterns of the thyroid hormonal changes in Graves' disease during the one-year period after 131I therapy considering that few serial hormonal data during this period are available in the literature. METHODS: The levels of serum T3, T4 and FT4 before and during one year were plotted as a function of time in 70 therapy courses of 58 patients without subsequent antithyroid or steroid therapy. RESULTS: 35 euthyroid, 6 hypothyroid and 29 hyperthyroid states were obtained during one year after therapy. Although individual patients had individual hormonal changing patterns, 3 common basic patterns were observed from baseline to one month (early) and thereafter (late), respectively. The early patterns were a decrease in 54 (77%), a minimum change in 8 (11.5%) and an increase in 8 (11.5%). The late patterns were a stable state after an initial decrease with a bottom followed by an increase (valley pattern) in 47 (67%), a stable state after an initial increase with a peak followed by a decrease with a bottom and a subsequent re-increase (mountain pattern) in 12 (17%) and a late stable state after a gradual slow decrease without an obvious bottom near or till one year (downhill pattern) in 11 (16%). The bottom level and the degree of hormonal recovery from the bottom determined the stable euthyroid, hypothyroid or hyperthyroid state in 49 (86%) of 57 with the valley or mountain pattern. Most of the bottom levels (81%) and transient abnormal changes including transient hypothyroidism (93%, 13/14), peak or hyperthyroidism (85%, 11/13) and euthyroidism (67%, 10/15) appeared within 6 months. The post-therapeutic stable euthyroid, hypothyroid or hyperthyroid state could be judged from the hormonal patterns in 57% (39/68) from 2.5 to 6 months, in 18% (12/68) from 6 to 9 months and in 25% (17/68) thereafter. CONCLUSION: Although the changes in thyroid hormones are not constant in Graves' disease during one year after 131I therapy, there are three basic patterns; valley, mountain and downhill patterns from one month after therapy. The post-therapeutic stable state can be judged by the hormonal level recovered from the bottom in most patients.     

A comparative study of the accuracy of Ranawat’s and Pierchon’s methods to determine the centre of rotation in bilateral coxopathy

Objective. The objective of the study was to compare two methods (Ranawat’s and Pierchon’s) used to determine the centre of rotation of the hip and establish which method calculates a position nearer to the real centre of rotation. Patients and design. We selected 24 patients with unilateral osteoarthritis of the hip. The centre of rotation of the healthy hip was determined in two consecutive radiographic studies by superimposing a template of circles and using two axes as the reference lines (X-axis=teardrop line; Y-axis=a line perpendicular to the X-axis, drawn from the intersection of the ilio-ischiatic line and the teardrop line). After ensuring the stability of these references, both methods were applied to the same radiograph to determine which one established a centre of rotation nearer to the anatomical centre identified by the template of circles. Results. When the values for the healthy hip are compared with those obtained using Ranawat’s method, highly significant differences are observed for both X (P<0.0001) and Y (P<0.0001). When the results for the healthy hip are compared with the values obtained using Pierchon’s method, neither the X (P=0.722 ) nor the Y values (P=0.112) show any significant differences. It would be advisable to use Pierchon’s method to determine the centre of rotation during the preoperative planning for a total hip arthroplasty when the anatomical alteration is bilateral. Received: 16 March 2000 Revision requested: 16 June 2000 Revision received: 31 July 2000 Accepted: 10 August 2000     

The effect of short-term treatment with lithium carbonate on the outcome of radioiodine therapy in patients with long-lasting Graves’ hyperthyroidism

Objective

The outcome of radioiodine therapy (RIT) in Graves’ hyperthyroidism (GH) mainly depends on radioiodine (¹³¹I) uptake and the effective half-life of ¹³¹I in the gland. Studies have shown that lithium carbonate (LiCO₃) enhances the ¹³¹I half-life and increases the applied thyroid radiation dose without affecting the thyroid ¹³¹I uptake. We investigated the effect of short-term treatment with LiCO₃ on the outcome of RIT in patients with long-lasting GH, its influence on the thyroid hormones levels 7 days after RIT, and possible side effects.

Methods

Study prospectively included 30 patients treated with LiCO₃ and ¹³¹I (RI-Li group) and 30 patients only with ¹³¹I (RI group). Treatment with LiCO₃ (900 mg/day) started 1 day before RIT and continued 6 days after. Anti-thyroid drugs withdrawal was 7 days before RIT. Patients were followed up for 12 months. We defined a success of RIT as euthyroidism or hypothyroidism, and a failure as persistent hyperthyroidism.

Results

In RI-Li group, a serum level of Li was 0.571?±?0.156 mmol/l before RIT. Serum levels of TT₄ and FT₄ increased while TSH decreased only in RI group 7 days after RIT. No toxic effects were noticed during LiCO₃ treatment. After 12 months, a success of RIT was 73.3% in RI and 90.0% in RI-Li group (P?<?0.01). Hypothyroidism was achieved faster in RI-Li (1st month) than in RI group (3rd month). Euthyroidism slowly decreased in RI-Li group, and not all patients became hypothyroid for 12 months. In contrast, euthyroidism rapidly declined in RI group, and all cured patients became hypothyroid after 6 months.

Conclusion

The short-term treatment with LiCO₃ as an adjunct to ¹³¹I improves efficacy of RIT in patients with long-lasting GH. A success of RIT achieves faster in lithium-treated than in RI group. Treatment with LiCO₃ for 7 days prevents transient worsening of hyperthyroidism after RIT. Short-term use of LiCO₃ shows no toxic side effects.

     

Is there a need for contrast-enhanced T1-weighted MRI of the spine after inconspicuous short τ inversion recovery imaging?

To assess the use of contrast-enhanced T1-weighted images in comparison with short inversion recovery (STIR) images for the detection of vertebral bone marrow abnormalities. A total of 201 vertebral magnetic resonance (MR) examinations were included in a prospective trial. Examinations were performed on a 0.5-T MR scanner. The examination protocol included STIR, T2-weighted turbo spin-echo and T1-weighted spin-echo images before and after administration of gadopentetate dimeglumine. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of STIR images were calculated. In the case of abnormal STIR images the additional information from contrast-enhanced images was evaluated using Fishers exact test. The value of the combined evaluation of STIR and contrast-enhanced T1-weighted images was compared with that of the combined assessment of T2-weighted and contrast-enhanced T1-weighted images. The PPV and the NPV of STIR images for detection of vertebral bone marrow abnormalities were 99.3 and 95.9%. In the case of normal STIR images no relevant additional information was found with contrast-enhanced T1-weighted images, while in the case of abnormal STIR images significant supplementary information was obtained. There was no difference in the diagnostic value when comparing combined assessment of STIR and contrast-enhanced T1-weighted images with combined evaluation of T2-weighted and contrast-enhanced T1-weighted images. Normal STIR images allow contrast-enhanced T1-weighted images for detection of bone marrow abnormalities to be omitted, whereas further imaging is needed in case of abnormal STIR images.