Fibrous dysplasia: A tale of two syndromes.

Fibrous dysplasia (FD) is a rare, non-inherited, congenital bone disorder which may be monostotic or polyostotic. The polyostotic form may rarely present in syndromic forms when associated with extra-skeletal manifestations. Mazabraud syndrome is a rare syndrome consisting of polyostotic FD presenting with intramuscular myxomas. McCune-Albright syndrome is recognised by polyostotic FD, precocious puberty and 'café au lait' spots. This report describes an adult patient with Mazabraud syndrome and a child with McCune-Albright syndrome. Contribution: Radiographic findings are typical with bowing deformities, sclerotic, lucent or mixed lesions and bony expansion, often with endosteal scalloping. MRI is often non-contributory and may actually mimic a more aggressive process. Early detection and correct diagnosis allow for early preventative treatment and rehabilitation to prevent devastating neurological sequelae and disability.

The effectiveness of the pregnancy adapted YEARS algorithm to safely identify patients for CT pulmonary angiogram in pregnant and puerperal patients suspected of having pulmonary embolism.

Background: Pulmonary thromboembolism is one of the leading causes of maternal death worldwide. Globally there has been increasing physician reliance on CT pulmonary angiogram for definitive diagnoses and exclusion of pulmonary thromboembolism. The problem, however, arises when considering the high radiation penalty from performing these investigations, highlighted by the low diagnostic yield. Of recent, the pregnancy-adapted YEARS algorithm has shown promise in international studies as a possible alternative for stratifying risk of pulmonary thromboembolism during the pregnancy and puerperal period. Objectives: To determine the effectiveness of the pregnancy adapted YEARS algorithm to safely minimise the number of true negative CT pulmonary angiograms for patients suspected of having pulmonary embolism in our clinical setting. Method: A cross-sectional study was performed in a tertiary hospital in Gauteng on puerperal and pregnant patients suspected of having pulmonary embolism. We retrospectively applied the pregnancy adapted YEARS algorithm and reviewed the various outcomes. Results: The pregnancy adapted YEARS algorithm proved effective in safely identifying patients for CT pulmonary angiography. By retrospectively applying the algorithm, there could have been a 25.7% scan reduction, whilst maintaining a negative predictive value of 100.0%. Conclusion: As physician reliance on radiological investigations increases, we must remain cognisant of the added radiation exposure and the long-term adverse effects of ionising radiation. The pregnancy-adapted YEARS algorithm provides a safe, reproducible alternative to aid our bid going forward.

Primary giant cell tumour of the breast with recurrence: A rare case report.

Giant cell tumour (GCT) arising from the soft tissues of the breast is a rare disease with only eight cases previously reported in the literature. We present a case of histologically proven GCT of the breast, which demonstrated recurrence a few months after resection.

Neuro-Behçet - Clinical and radiological findings in a Patient of Sub-saharan African origin.

Behçet's disease is a rare, systemic variable vessel vasculitis mostly seen in patients from the Middle East, Northern Africa and Central Asia. Neuro-Behçet disease (NBD) is often diagnosed in patients with known Behçet's disease who present with neurological symptoms and radiological features of central nervous system involvement. There are very few cases with neuro-Behçet reported from Sub-Saharan Africa in the literature. We report a case of severe parenchymal neuro-Behçet with pseudo-tumoral brainstem lesions in a young male patient of South African origin.

Effects of delta-tocotrienol supplementation on glycaemic control in individuals with prediabetes: A randomized controlled study.

OBJECTIVE: To study the effects of delta-tocotrienol on glycaemic control parameters in individuals with pre-diabetes. METHODS: The randomised control trial was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from July 15 to November 15, 2019, and comprised individuals aged 18-60 years having fasting plasma glucose of 5.6 to 6.9 mmol/L or glycosylated haemoglobin of 5.7 to 6.4%. They were randomised into group A receiving 300mg delta-tocotrienol and group B receiving a placebo once daily for 12 weeks. Weight, height, waist circumference, fasting plasma glucose, insulin and glycosylated haemoglobin were measured at the beginning and end of the trial to assess any change. Body mass index and homeostatic model assessment-insulin resistance were also calculated. Data was analysed using SPSS 21. RESULTS: Of the 77participants, 40(52%) were in group A and 37(48%) in group B. Group A showed significantly greater reduction in terms of fasting plasma glucose, glycosylated haemoglobin, insulin and homeostatic model assessment-insulin resistance index (p≤0.001) post-intervention. CONCLUSIONS: Delta-tocotrienol supplementation was found to have a significant effect in improving glycaemic control parameters in persons with pre-diabetes. Futures larger scale clinical trials are needed to confirm these findings. CLINICAL TRIAL NUMBER: SLCTR/2019/024.

Medullary neuroschistosomiasis in a pediatric patient: a case report.

A pediatric patient with neurological deficit was examined using magnetic resonance imaging (MRI]. The images revealed abnormal signal intensity and enhancement of the spinal cord, indicating myelopathy. Identifying the cause of the myelopathy required a differential diagnosis. Images from MRI included a pre-contrast T1 weighted sagittal sequence, which revealed expansion of the distal lumbar spinal cord and conus medullaris from T10-L1. The T2 weighted sagittal sequence revealed patchy areas of hyperintense signal. We did not notice any chronic hemorrhagic products or cysts. Within the field of view, we saw multifocal areas of bladder wall thickening. Sagittal and axial T1 weighted post gadolinium images demonstrated mixed linear and nodular patchy enhancement of the conus medullaris predominantly anteriorly and along the anterior surface of the meninges. On the 18 day of hospitalization, a spinal biopsy revealed the presence of granuloma with non-viable bilharzia ova, and schistosomiasis of the spinal cord was diagnosed. Although uncommon, when it does occur, schistosomiasis has significant implications. Using MRI, the medical team noticed abnormal features that called for a biopsy, and were thus able to differentiate between medullary schistosomiasis and other infective/inflammatory conditions. A prompt diagnosis is vital for initiating early treatment, and avoiding complications and invasive surgery.

Foetal magnetic resonance imaging: A necessity or adjunct? A modality comparison of in-utero ultrasound and ultrafast foetal magnetic resonance imaging.

BACKGROUND: Congenital anomalies occur in approximately 2% of newborns, resulting in severe medical, physical and social disabilities. Managing clinicians, therefore, require more confidence in their diagnosis and prognostic accuracy before appropriately counselling the parents regarding termination of pregnancy. OBJECTIVE: The aim of this study was to investigate the role of magnetic resonance imaging (MRI) following the diagnosis of foetal anomalies at a foetomaternal unit of a tertiary South African institution. METHODS: Eighty-eight pregnant women in their late second/third trimester who underwent both an ultrasound (US) at the foetomaternal unit and foetal MRI at the Radiology Department from 01 July 2013 to 30 September 2019 were included in this clinical study conducted at Steve Biko Academic Hospital. RESULTS: Despite the high degree of concurrence (73.9%) between both modalities regarding the main diagnoses, MRI provided additional information in 45.5% of patients and changed the diagnosis in 25% of the patients. It further demonstrated superiority in providing diagnostic information in 97% of cases where the US alone was inadequate to counsel parents regarding the termination of pregnancy, and it completely changed the clinical management in 42% of cases. CONCLUSION: It is clearly evident from this study that foetal MRI is a necessity when termination of pregnancy is being considered following an US conducted by the foetomaternal unit. This allows for a complete foetal assessment and gives the managing clinician sufficient diagnostic confidence to prognosticate the future quality of life of the child.

Are endocasts reliable proxies for brains? A 3D quantitative comparison of the extant human brain and endocast.

Endocasts (i.e., replicas of the inner surface of the bony braincase) constitute a critical proxy for qualifying and quantifying variations in brain shape and organization in extinct taxa. In the absence of brain tissues preserved in the fossil record, endocasts provide the only direct evidence of brain evolution. However, debates on whether or not information inferred from the study of endocasts reflects brain shape and organization have polarized discussions in paleoneurology since the earliest descriptions of cerebral imprints in fossil hominin crania. By means of imaging techniques (i.e., MRIs and CT scans) and 3D modelling methods (i.e., surface-based comparisons), we collected consistent morphological (i.e., shape) and structural (i.e., sulci) information on the variation patterns between the brain and the endocast based on a sample of extant human individuals (N = 5) from the 3D clinical image database of the Steve Biko Academic Hospital in Pretoria (South Africa) and the Hôpitaux Universitaires Pitié Salpêtrière in Paris (France). Surfaces of the brain and endocast of the same individual were segmented from the 3D MRIs and CT images, respectively. Sulcal imprints were automatically detected. We performed a deformation-based shape analysis to compare both the shape and the sulcal pattern of the brain and the endocast. We demonstrated that there is close correspondence in terms of morphology and organization between the brain and the corresponding endocast with the exception of the superior region. By comparatively quantifying the shape and organization of the brain and endocast, this work represents an important reference for paleoneurological studies.

Simple Erosion Narrowing Score of the hands as a predictor of cervical spine subluxation in rheumatoid arthritis.

BACKGROUND: Involvement of the cervical spine is common in patients with rheumatoid arthritis and can lead to devastating or even fatal consequences. Currently no guidelines exist as to whether radiographs of the cervical spine should be included in follow-up visits. OBJECTIVES: To determine whether the Simple Erosion Narrowing Score (SENS) of the hands correlate with the presence of cervical spine subluxation in patients with rheumatoid arthritis. METHOD: This was a retrospective, observational, cross-sectional study. A total of 56 rheumatoid arthritis patients with hand radiographs and lateral radiographs of the cervical spine were evaluated. The SENS of the hands and the presence of cervical spine subluxation were compared. The SENS of the hands was correlated with the prevalence of cervical spine subluxation, as was the erosion and joint space narrowing scores of the hands. RESULTS: A correlation between the SENS of the hands and the prevalence of cervical spine subluxation was confirmed. A higher prevalence of cervical spine subluxation correlated with an increase in the SENS of the hands (p = 0.0002). The erosion and joint space narrowing scores of the hands also correlated with the prevalence of cervical spine subluxation (p = 0.0001). CONCLUSION: This study confirmed that a correlation exists between cervical spine subluxation, peripheral joint space erosions and joint space narrowing in patients with rheumatoid arthritis and SENS may therefore be used as a predictor of cervical spine disease.

The Association Between Anterior Cruciate Ligament Length and Femoral Epicondylar Width Measured on Preoperative Magnetic Resonance Imaging or Radiograph.

PURPOSE: To determine whether femoral epicondylar width (FECW) obtained from either magnetic resonance imaging (MRI) or plain radiographs could be used to predict anterior cruciate ligament (ACL) length. A secondary purpose was to develop a formula to use maximum FECW on either MRI or plain radiographs to estimate ACL length preoperatively. METHODS: The MRIs and radiographs of 40 patients (mean age 41.0 years), with no apparent knee pathology, surgery, or trauma were included. The ACL length was measured on MRI followed by FECW on both MRI and radiograph of the same patient. This allowed the development of equations able to predict ACL length according to the FECW measured on either an MRI or radiograph. RESULTS: The mean ACL length was 40.6 ± 3.6 mm. FECW measured on both MRIs and radiographs was sufficient to predict ACL length. Pearson's correlations revealed a high positive relationship between ACL length and FECW on MRI (r = 0.89, P < .0001) and ACL length and FECW on radiograph (r = 0.83, P < .0001). The coefficient of determination (R2) was calculated to be MRI: R2 = 0.78 and radiograph: R2 = 0.68 and confirmed that FECW measured on both MRI and radiograph were sufficient to predict ACL length. Based on these models, ACL length can be predicted by FECW using the following formulas: MRI: ACL length = 0.47 (FECW) + 1.93 and radiograph: ACL length = 0.31 (FECW) + 11.33. CONCLUSIONS: This study demonstrated that FECW measured on either MRI or anteroposterior radiograph could reliably estimate ACL length on a sagittal MRI. There was a high positive relationship between ACL length and FECW on both MRI and radiographs, although MRIs do predict ACL length more reliably. CLINICAL RELEVANCE: Preoperative ACL length assessment, using FECW on MRI or radiograph, is useful in graft selection and in preventing inadequate graft harvesting for ACL reconstruction, especially if an individualized anatomical approach is pursued.

The knowledge, awareness and practices of radiation safety amongst orthopaedic surgeons.

BACKGROUND: Fluoroscopic imaging in orthopaedic theatres is increasing, with added risk to the orthopaedic surgeon who is increasingly being exposed to ionising radiation. It is thus crucial for orthopaedic surgeons to have a working knowledge of radiation safety. In spite of these concerns, however, many orthopaedic surgeons do not receive standard training in radiation safety. OBJECTIVES: The evaluation of orthopaedic surgeons' knowledge, awareness and everyday practices regarding radiation safety in an academic hospital. METHODS: A questionnaire with multiple-choice-type questions was developed by a panel of experts and used to conduct a descriptive study. The questionnaire had multiple dimensions, each evaluating orthopaedic knowledge, awareness and practices, respectively. The study population included orthopaedic surgeons rotating within the orthopaedic circuit of the University of Pretoria. RESULTS: Orthopaedic surgeons regularly make use of fluoroscopic imaging in theatre, with 34 (77%) participants indicating that they use fluoroscopy in more than half of all their procedures performed. Most participants have insufficient knowledge of radiation safety, with the majority failing to correctly answer basic questions on radiation safety. Forty (91%) participants do not wear personal dosimeters, in spite of 39 participants (89%) believing that they are vulnerable to adverse effects. Basic radiation protection devices are underutilised, with 32 (73%) participants indicating that they have not received adequate training in radiation safety. CONCLUSION: The majority of orthopaedic surgeons regularly use fluoroscopic imaging in theatre yet lack in-depth knowledge and awareness regarding radiation safety associated with this imaging modality. Implementation of a radiation safety training programme is thus recommended.

Outcomes of prostate artery embolisation for benign prostatic hyperplasia in 10 cases at Steve Biko Academic Hospital.

BACKGROUND: Benign prostate hyperplasia (BPH) remains a common cause of lower urinary tract symptoms (LUTS) in ageing men in South Africa and can impact significantly on the quality of life (QOL) of these patients. The Urology Department at Steve Biko Academic Hospital (SBAH) can generally only offer men with LUTS the following treatment options: watchful waiting, medical treatment and surgical management. In men with symptomatic BPH, who are refractory to medical treatment, where anaesthesia is contra-indicated because of co-morbidities or transurethral resection of the prostate (TURP) is contra-indicated because of the prostate size, the Urology and Radiology departments at SBAH recently introduced prostate artery embolisation (PAE). AIM: To assess the outcome of PAE in 10 men with LUTS, secondary to BPH, by comparing their urinary symptoms, QOL and prostate volume before and 3 months after they underwent PAE in the Radiology Department at SBAH. METHOD: The review included the first 10 men who had undergone therapeutic PAE for symptomatic BPH from May 2016 to September 2016. The subjective symptomatic feedback was assessed according to the International Prostate Symptom Score (IPSS) and the Global Quality of Life questionnaire, created by the American Urological Association (AUA). The reduction in the size of the prostate was measured on magnetic resonance imaging (MRI). RESULTS: Embolisation was technically achieved in all 10 patients. Bilateral embolisation was performed on nine patients. One patient received unilateral embolisation secondary to unilateral tortuous and atherosclerotic changes of the iliac arteries. Within the 3-month follow-up, the mean IPSS score improved by 15.7 points (p < 0.0039), the mean QOL improved by 4.1 points (p < 0.0039) and the mean prostate volume reduction was 21.8 mL (p < 0.0039). Despite improvements observed, there was one clinical failure. No major complications were reported that increased hospital stay, required hospital readmission or required surgery. CONCLUSION: The study on the first 10 PAE performed in SBAH concludes that PAE is a safe and effective procedure with favourable short-term follow-up results. This indicates that PAE can safely be offered to patients, who are refractory to medical treatment and not suitable candidates for surgery, in urology departments such as in SBAH.

Meralgia paresthetica: Now showing on 3T magnetic resonance neurography.

Meralgia paresthetica is a neuropathy of the lateral femoral cutaneous nerve. Traditionally, the diagnosis is based on classical symptoms and signs. In cases where there is a diagnostic dilemma, the role of magnetic resonance imaging has been to exclude other causes for the patient's presentation, as the small extraspinal peripheral nerves were not well visualised at imaging. The development of 3-Tesla magnetic resonance neurography, however, has made pathology of these nerves more conspicuous.

The accuracy of magnetic resonance imaging diagnosis of non-osseous knee injury at Steve Biko Academic Hospital.

BACKGROUND: Preoperative magnetic resonance imaging (MRI) has internationally been proven to reduce unnecessary knee arthroscopies and assist with surgical planning. This has the advantage of avoiding unnecessary surgery and the associated anaesthetic risk, as well as reducing costs. No data were found in the recently published literature assessing the accuracy of MRI interpretation of knee ligament injury in the public sector locally. OBJECTIVES: This pilot study aimed to determine the accuracy of MRI in detecting non-osseous knee injury in a resource-limited tertiary-level academic hospital in Pretoria, South Africa, compared to the gold standard arthroscopy findings. METHOD: This was an exploratory retrospective analysis of 39 patients who had MRI and arthroscopy at Steve Biko Academic Hospital (SBAH). True positive, true negative, false positive and false negative results were extrapolated from findings in both modalities and translated into sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each structure. RESULTS: Negative predictive values were recorded as 97%, 81%, 90% and 100% (anterior cruciate ligament [ACL], medial meniscus [MM], lateral meniscus [LM] and posterior cruciate ligament [PCL], respectively), which were comparative to recently published international literature. The PPV results were lower than those previously evaluated at 55%, 58%, 55% and not applicable. The sensitivities and specificities of the ligaments were 83%, 58%, 83% and not applicable; and 87%, 81%, 70% and not applicable, respectively. CONCLUSION: Magnetic resonance imaging was found to be sensitive and specific, with a high NPV noted in all structures evaluated. Negative results can therefore be used to avoid unnecessary surgery to the benefit of the patient and state. The study reiterates that high accuracy can be obtained from MRI on a 1.5-tesla non-dedicated scanner, with interpretation by generalist radiologists.

Apprasial of the surface anatomy of the Thorax in an adolescent population.

Surface anatomy is considered a fundamental part of anatomy curricula and clinical practice. Recent studies have reappraised surface anatomy using CT, but the adolescent age group has yet to be appraised. Sixty adolescent thoracoabdominal CT scans (aged 12-18 years) were examined. The surface anatomy of the central veins, cardiac apex, diaphragmatic openings, and structures in relation to the sternal angle plane were analyzed. The results showed that the brachiocephalic vein (left and right) formed mostly posterior to the sternoclavicular joint. The superior vena cava formed close to the second costal cartilage, ±16.3 mm to the right of the midline. The apex of the heart was located in relation to the fifth intercostal space; ±78.6 mm to the left of the midline. The caval hiatus was in relation to T9 and T10; the esophageal hiatus was at T10; whereas the aortic hiatus was at T11. The sternal angle plane was in relation to the upper half of T5, which was also where the bifurcations of the trachea and pulmonary trunk were observed. The SVC/azygos vein junction and the concavity of the aortic arch were observed to be more than 10 mm superior to this plane. The results of this study further highlight the substantial variability of the surface anatomy between age groups. It also emphasizes the notion that surface anatomy is a dynamic variable and cannot be treated as a static observation. Clin. Anat. 32:762-769, 2019. © 2019 Wiley Periodicals, Inc.

Outcomes of prostate artery embolisation for benign prostatic hyperplasia in 10 cases at Steve Biko Academic Hospital

Background: Benign prostate hyperplasia (BPH) remains a common cause of lower urinary tract symptoms (LUTS) in ageing men in South Africa and can impact significantly on the quality of life (QOL) of these patients. The Urology Department at Steve Biko Academic Hospital (SBAH) can generally only offer men with LUTS the following treatment options: watchful waiting, medical treatment and surgical management. In men with symptomatic BPH, who are refractory to medical treatment, where anaesthesia is contra-indicated because of co-morbidities or transurethral resection of the prostate (TURP) is contra-indicated because of the prostate size, the Urology and Radiology departments at SBAH recently introduced prostate artery embolisation (PAE). Aim: To assess the outcome of PAE in 10 men with LUTS, secondary to BPH, by comparing their urinary symptoms, QOL and prostate volume before and 3 months after they underwent PAE in the Radiology Department at SBAH. Method: The review included the first 10 men who had undergone therapeutic PAE for symptomatic BPH from May 2016 to September 2016. The subjective symptomatic feedback was assessed according to the International Prostate Symptom Score (IPSS) and the Global Quality of Life questionnaire, created by the American Urological Association (AUA). The reduction in the size of the prostate was measured on magnetic resonance imaging (MRI). Results: Embolisation was technically achieved in all 10 patients. Bilateral embolisation was performed on nine patients. One patient received unilateral embolisation secondary to unilateral tortuous and atherosclerotic changes of the iliac arteries. Within the 3-month follow-up, the mean IPSS score improved by 15.7 points (p< 0.0039), the mean QOL improved by 4.1 points (p < 0.0039) and the mean prostate volume reduction was 21.8 mL (p < 0.0039). Despite improvements observed, there was one clinical failure. No major complications were reported that increased hospital stay, required hospital readmission or required surgery. Conclusion: The study on the first 10 PAE performed in SBAH concludes that PAE is a safe and effective procedure with favourable short-term follow-up results. This indicates that PAE can safely be offered to patients, who are refractory to medical treatment and not suitable candidates for surgery, in urology departments such as in SBAH

The validity of arterial measurements in a South African embalmed body population.

INTRODUCTION: Knowledge of the normal arterial diameter at a given anatomical point is the first step toward quantifying the severity of cardiovascular diseases. According to several studies, parameters such as weight, height, age and sex can explain morphometric variations in arterial anatomy that are observed in a population. Before the development of a reference database against which to compare the diameters of arteries in a variety of pathological conditions, the compatibility between embalmed body measurements and computed tomography (CT) measurements must first be established. PURPOSE: The aim of this study was to compare embalmed body measurements and CT measurements at 19 different arterial sites to establish whether embalmed body measurements are a true reflection of a living population. METHODS: A total of 154 embalmed bodies were randomly selected from the Department of Anatomy at the University of Pretoria and 36 embalmed bodies were randomly selected from the Department of Human Anatomy at the University of Limpopo, Medunsa Campus. Dissections were performed on the embalmed body sample and the arterial dimensions were measured with a mechanical dial-sliding caliper (accuracy of 0.01 mm). 30 CT images for each of the 19 arterial sites were retrospectively selected from the database of radiographic images at the Department of Radiology, Steve Biko Academic Hospital. Radiant, a Digital Imaging and Communications in Medicine (DICOM) viewer was used to analyze the CT images. RESULTS: The only statistically significant differences between the embalmed body measurements and CT measurements were found in the left common carotid- and the left subclavian arteries. The null hypothesis of no statistically significant difference between the embalmed body and CT measurements was accepted since the P value indicated no significant difference for 87% of the measurements, the exception being the left common carotid- and the left subclavian arteries. CONCLUSIONS: With the exception of two measurements, measurements in embalmed bodies and living people are interchangeable and concerns regarding the effect of distortion and shrinkage are unfounded. Even small changes in arterial diameter greatly influence blood flow and blood pressure, which contribute to undesirable clinical outcomes such as aortic aneurysms and aortic dissections. This study completes the first step towards the development of a reference database against which to compare the diameters of arteries in a variety of pathological conditions in a South African population.

The role of imaging in rheumatoid arthritis.

Conventional radiographs of the hands and feet have traditionally been used in the diagnosis, management and monitoring of patients with rheumatoid arthritis (RA). However, they are not sensitive enough to detect changes early in the disease process. Erosions may only be visible up to two years after the onset of disease, and soft tissue involvement may not be detected at all. Early diagnosis can also be made challenging as markers such as erythrocyte sedimentation rate and C-reactive protein may be normal in up to 20% - 25% of cases. The latest classification criteria (American College of Rheumatology/European League Against Rheumatism [ACR/EULAR] Rheumatoid Arthritis Classification criteria 2010), often used to diagnose RA, incorporate the role of ultrasound and magnetic resonance imaging detection of synovitis, enabling earlier diagnosis and correct classification of patients. This article looks at the role of the various imaging modalities used in the diagnosis and management of RA.

Disseminated Kaposi sarcoma presenting in unusual locations: A case report.

Kaposi sarcoma (KS) is the most common malignancy associated with HIV infection. It usually affects the skin, the gastrointestinal tract and the lungs. It is generally described in the setting of CD4 counts < 150 cells/mm3 - 200 cells/mm3. We describe a case of recurrence of KS with a rare presentation of breast and musculoskeletal involvement in the setting of a CD4 count of 374 cell/mm3 and an undetectable viral load. The patient was on highly active antiretroviral therapy for 5 years at the time of the second presentation.