Chronic T Cell Encephalitis Responsive to Immunotherapy.

Chronic encephalitis manifesting as an epilepsy syndrome most commonly presents as Rasmussen's syndrome, usually characterized by epilepsia partialis continua, hemiparesis, and progressive cortical deficits such as aphasia, hemianopia, and cognitive decline. It is characterized by progressive hemispheric cortical atrophy on imaging and is usually seen in childhood. Adult-onset of the syndrome is rare, and only a few cases have been reported with bilateral symptoms. We present a patient with pseudobulbar affect and frontal lobe dysfunction who developed multifocal myoclonic jerks, right hemibody focal motor seizures, and right hemiparesis with bilateral cerebellar signs. Magnetic resonance imaging showed progressive hemispheric atrophy and bilateral features in Positron emission tomography-computed tomography (PET CT). Brain biopsy revealed chronic T-cell infiltrate. We discuss this case as the patient had several features that were atypical for Rasmussen's encephalitis (or syndrome).

Diagnostic added value of interictal magnetic source imaging in presurgical evaluation of persons with epilepsy: A prospective blinded study.

BACKGROUND AND PURPOSE: In presurgical evaluation for epilepsy surgery, information is sourced from various imaging modalities to accurately localize the epileptogenic zone. Magnetoencephalography (MEG) is a newer noninvasive technique for localization. However, there is limited literature to evaluate if MEG provides additional advantage over the conventional imaging modalities in clinical decision making. The objective of this study was to assess the diagnostic added value of MEG in decision making before epilepsy surgery. METHOD: This was a prospective observational study. Patients underwent 3 h of recording in a MEG scanner, and the resulting localizations were compared with other complimentary investigations. Added value of MEG (considered separately from high-density electroencephalography) was defined as the frequency of cases in which (i) the information provided by magnetic source imaging (MSI) avoided implantation of intracranial electrodes and the patient was directly cleared for surgery, and (ii) MSI indicated additional substrates for implantation of intracranial electrodes. Postoperative seizure freedom was used as the diagnostic reference by which to measure the localizing accuracy of MSI. RESULTS: A total of 102 patients underwent epilepsy surgery. MEG provided nonredundant information, which contributed to deciding the course of surgery in 33% of the patients, and prevented intracranial recordings in 19%. A total of 76% of the patients underwent surgical resection in sublobes concordant with MSI localization, and the diagnostic odds ratio for good (Engel I) outcome in these patients was 2.3 (95% confidence interval 0.68, 7.86; p = 0.183) after long-term follow-up of 36 months. CONCLUSION: Magnetic source imaging yields additional useful information which can significantly alter as well as improve the surgical strategy for persons with epilepsy.

Comparative contribution of magnetoencephalography (MEG) and single-photon emission computed tomography (SPECT) in pre-operative localization for epilepsy surgery: A prospective blinded study.

PURPOSE: The aim of this study was to compare the diagnostic value and accuracy of ictal SPECT and inter-ictal magnetoencephalography (MEG) in localizing the site for surgery in persons with drug resistant epilepsy. METHOD: This was a prospective observational study. Patients expected to undergo epilepsy surgery were enrolled consecutively and the localization results from different imaging modalities were discussed in an epilepsy surgery meet. Odds ratio of good outcome (Engel I) were calculated in patients who underwent surgery in concordance with MEG and SPECT findings. Post-surgical seizure freedom lasting at least 36 months or more was considered the gold standard for determining the diagnostic output of SPECT and MEG. RESULTS: MEG and SPECT were performed in 101 and 57 patients respectively. In 45 patients SPECT could not be done due to delay in injection or technical factors. The accuracy of MEG and SPECT in localizing the epileptogenic zone was found to be 74.26 % and 78.57 % respectively. The diagnostic odds ratio for Engel I surgical outcome was reported as 2.43 and 5.0 for MEG and SPECT respectively. The diagnostic odds ratio for MEG in whom SPECT was non-informative was found to be 6.57 [95 % CI 1.1, 39.24], although it was not significantly associated with good surgical outcome. MEG was useful in indicating sites for SEEG implantation. CONCLUSION: SPECT was found to be non-informative for most patients, but reported better diagnostic output than MEG. MEG may be a useful alternative for patients in whom SPECT cannot be done or was non-localizing.

Progression of Chronic Pancreatitis to Pancreatic Cancer: Is There a Role of Gene Mutations as a Screening Tool?

OBJECTIVES: Early detection of pancreatic ductal adenocarcinoma still remains a challenge. Patients with chronic pancreatitis (CP) have a markedly increased risk of pancreatic cancer. Mutations in oncogenes and/or tumor suppressor genes play a role in development of pancreatic ductal adenocarcinoma. This study assessed mutations in KRAS and p53 gene in blood as a screening tool for malignant transformation in CP patients. METHODS: This was a cohort, single-center study including 294 CP patients. DNA was isolated from plasma of CP patients, and KRAS mutations were identified using polymerase chain reaction-restriction fragment length polymorphism. Patients with positive KRAS mutation were screened for malignancy using positron emission tomography or endoscopic ultrasound. Mutations in p53 gene were analyzed by sequencing. Tissue samples from CP and pancreatic cancer patients were also tested for mutations in KRAS and p53 genes. RESULTS: The plasma samples of 64 CP patients were positive for KRAS mutation, and 4 had mutation in p53 gene also. No patient positive for KRAS mutation and/or p53 mutation was found to have malignant transformation. CONCLUSION: Detection of KRAS or p53 mutation in plasma is not an effective screening tool for pancreatic cancer because accumulation of multiple mutations is required for malignant transformation in the pancreas.

Peptide Receptor Radionuclide and Octreotide: A Novel Approach for Metastatic Tumor-Induced Osteomalacia.

KEY MESSAGES: Octreotide can be used as an adjunctive therapy to increase phosphorus levels in patients with tumor-induced osteomalacia. Malignant phosphaturic mesenchymal tumor (PMT) may benefit from treatment with peptide receptor radionucleotide therapy. CONTEXT: The success of treatment modalities for malignant PMT is limited. Octreotide has been used to treat hypophosphatemia in patients with tumor-induced osteomalacia with equivocal results. To our knowledge, there are no reports of octreotide or peptide receptor radionuclide therapy use for malignant PMT. CASE DESCRIPTION: We report a 40-year-old man having hypophosphatemia, phosphaturia (tubular maximum of phosphorus corrected for glomerular filtration rate of <2.5 mg/dL), and somatostatin avid lesions in the right foot region with metastasis to both lungs. The patient had been subjected to resection of the primary tumor from the foot with thoracoscopic removal of the lung secondaries. Histology from all three lesions showed a spindle cell soft tissue tumor with a high mitotic index and somatostatin receptor 2 and 5 positivity. A trial of subcutaneous octreotide therapy at a dose of 100 µg thrice daily resulted in an increase in serum phosphorus levels from an average of 1.44 mg/dL to an average of 2.3 mg/dL. Finally, the affected limb was amputated, and the hypophosphatemia persisted postoperatively. In view of persistent hypophosphatemia and transient response to octreotide, the patient was administered four cycles of peptide receptor radionuclide therapy using 177Lutetium, which showed moderate improvement of serum phosphorus levels. CONCLUSION: Although octreotide use has been reported in four patients with benign PMT, to our knowledge, this is the first case of malignant PMT that has used peptide receptor radionuclide therapy in the treatment of malignant PMT. This moderately beneficial evidence is likely to guide the future use of radionuclide treatments in such tumors.

Role of various semiquantitative parameters of 18F-FDG PET/CT studies for interim treatment response evaluation in non-small-cell lung cancer.

PURPOSE: The aim of this study was to prospectively evaluate the role of various semiquantitative parameters obtained from fluorine-18 fluorodeoxyglucose (F-FDG) PET/CT in interim treatment response assessment in biopsy-proven non-small-cell lung cancer (NSCLC) and to find the best parameter, if any. MATERIALS AND METHODS: Totally, 32 patients (male/female: 25/7) with biopsy proven NSCLC and a mean age of 54.71±12.65 years were enrolled in the study. Each patient underwent whole-body F-FDG PET/CT scan after injecting 5.18-7.77 MBq/kg of F-FDG intravenously at baseline and after four cycles of chemotherapy. Five parameters - that is, target-to-background ratio (TBR), maximum standardized uptake value (SUVmax), average standardized uptake value (SUVavg), whole-body metabolic tumor volume (MTVwb), and whole-body total lesion glycolysis (TLGwb) - were evaluated for both scans along with their percentage changes ([INCREMENT]). Patients were divided into two response groups as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria: responders and nonresponders. All parameters were compared among the two response groups using appropriate statistical methods; P value of less than 0.05 was considered significant. RESULTS: All postchemotherapy parameters were found to have a significant role in the prediction of two response groups. Post-TBR had highest area under the receiver operating characteristic curve of 0.83 with a sensitivity and specificity of 75 and 82%, respectively, at a cutoff value of 4. The [INCREMENT]s, [INCREMENT]MTVwb, [INCREMENT]TLGwb, and [INCREMENT]SUVmax were significant with cutoffs of -56, -75, and -32%, respectively. [INCREMENT]MTVwb had the highest area under the receiver operating characteristic curve of 0.83 with sensitivity and specificity of 81.25%. In multivariate analysis, post-TBR and [INCREMENT]MTVwb were found to be the independent variables for prediction of interim treatment response. CONCLUSION: Our study proves that a multitude of semiquantitative parameters as documented above differ significantly between two response groups in patients with advanced stage NSCLC receiving chemotherapy. Moreover, parameters in combination (ΔMTV and post-TBR) with appropriate cutoffs can predict response groups with acceptable reliability.

Primary hyperparathyroidism may masquerade as rickets-osteomalacia in vitamin D replete children.

Primary hyperparathyroidism, typically a disease of the middle aged and the old, is less commonly seen in children. In children the disease has a bimodal age distribution with calcium sensing receptor mutation presenting in infancy as hypercalcemic crises and parathyroid adenoma or hyperplasia presenting later in childhood with bone disease. The childhood parathyroid adenomas are often familial with multiglandular disease and manifest with severe bone disease unlike adults. We report a series of four male patients with juvenile primary hyperparathyroidism, three of whom presented with bone disease masquerading as rickets-osteomalacia. One patient had asymptomatic hypercalcemia with short stature. Parathyroid adenoma was detected in all the four cases and all of them underwent resection of parathyroid adenomas confirmed on histopathology. Post-surgery all the cases had initial hypocalcaemia followed by normocalcemia. One case developed pancreatitis after surgery even after achieving normocalcemia. We conclude that parathyroid adenomas, although uncommon in children, are an important cause of skeletal disease that may initially be confused with hypovitaminosis D.

Radioiodine Remnant Ablation: A Critical Review.

Radioiodine remnant ablation (RRA) is considered a safe and effective method for eliminating residual thyroid tissue, as well as microscopic disease if at all present in thyroid bed following thyroidectomy. The rationale of RRA is that in the absence of thyroid tissue, serum thyroglobulin (Tg) measurement can be used as an excellent tumor marker. Other considerations are like the presence of significant remnant thyroid tissue makes detection and treatment of nodal or distant metastases difficult. Rarely, microscopic disease in the thyroid bed if not ablated, in the future, could be a source of anaplastic transformation. On the other hand, microscopic tumor emboli in distant sites could be the cause of distant metastasis too. The ablation of remnant tissue would in all probability eliminate these theoretical risks. It may be noted that all these are unproven contentious issues except postablation serum Tg estimation that could be a good tumor marker for detecting early biochemical recurrence in long-term follow-up strategy. Radioactive iodine is administered as a form of "adjuvant therapy" for remnant ablation. There have been several reports with regard to the administered dose for remnant ablation. The first report of a prospective randomized clinical trial was published from India by a prospective randomized study conducted at the All India Institute of Medical Sciences, New Delhi in the year 1996. The study reported that increasing the empirical (131)I initial dose to more than 50 mCi results in plateauing of the dose-response curve and thus, conventional high-dose remnant ablation needs critical evaluation. Recently, two important studies were published: One from French group and the other from UK on a similar line. Interestingly, all three studies conducted in three different geographical regions of the world showed exactly similar conclusion. The new era of low-dose remnant ablation has taken a firm scientific footing across the continents.

Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases.

AIM: This study was aimed at identifying the prognostic factors predicting remission in pediatric differentiated thyroid cancer (DTC) patients presenting with pulmonary metastases. Little is known about the prognostic factors in reference to pediatric DTC patients presenting with pulmonary metastases. METHODS: Fifty-three DTC patients aged ≤21 years were diagnosed with pulmonary metastases at initial presentation. The demographic and disease characteristics were compared between the patients who achieved remission and those who did not. RESULTS: During the median follow-up of 72 months, 38 patients became disease free, 14 patients had biochemically and/or structurally persistent disease, and one patient died due to disease progression. Patient age >15 years, presence of macronodular pulmonary metastases, and surgical methods lesser than total/near-total thyroidectomy were identified as factors associated with reduced odds of remission. CONCLUSION: This study describes the disease course and depicts the disease related prognostic factors in pediatric DTC patients with pulmonary metastases.

Role of concordance between ictal-subtracted SPECT and PET in predicting long-term outcomes after epilepsy surgery.

OBJECTIVE: F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and ictally subtracted single photon emission tomography (iSPECT) are important for localizing the epileptogenic focus. The following study analyzes the role of inter-concordance between FDG-PET and iSPECT in predicting long-term outcomes after epilepsy surgery. METHODS: We prospectively evaluated (January 2003-January 2008) patients undergoing surgery for temporal or extratemporal drug refractory epilepsy (DRE) who had at least a 5 years follow up. Patients with MRI and video EEG (vEEG) concordance for the seizure focus underwent iSPECT and FDG-PET. Concordance of the iSPECT and FDG-PET with each other and with the substrate (defined by MRI and vEEG) for temporal and extra-temporal epilepsies was evaluated and correlated with outcomes. RESULTS: One hundred twenty-three patients (74 males) were included in the study (mean age at time of surgery: 18.9±10.41 years). The mean age of onset of seizures was 9.87±8.37 years. The most common semiology was complex partial (45%). When both FDG-PET and iSPECT were concordant with each other, this translated into a (class I Engel at 5 years) outcome of 62% for extra-temporal epilepsies (provided they were also concordant with the lesion, as defined by MRI and vEEG). This percentage was significant (p<0.01) compared with all other situations (both FDG-PET/iSPECT not concordant to MRI/vEEG, only PET or iSPECT concordant with MRI/vEEG). This correlation was not found for the temporal epilepsies, where the MRI and vEEG were the most important prognostic parameters. In both temporal and extratemporal epilepsies the concordance of the iSPECT/FDG-PET with the MRI/vEEG correlated with a better 5-year outcome (temporal: 70% vs 25%; extra-temporal: 62% vs 33%; p<0.05). SIGNIFICANCE: Concordance between non-invasive investigations iSPECT and FDG-PET is an important predictive factor for surgical outcomes in extra-temporal epilepsy.

Ectopic insulin secreting neuroendocrine tumor of kidney with recurrent hypoglycemia: a diagnostic dilemma.

BACKGROUND: Hypoglycemia secondary to ectopic insulin secretion of non-pancreatic tumors is rare. CASE PRESENTATION: We describe a middle aged woman with recurrent hypoglycemia. On evaluation, she was detected to have hyperinsulinemic hypoglycemia and right sided renal mass lesion. 68Ga-Dotanoc and 99mTc-HYNICTOC scans confirmed the intrarenal mass to be of neuroendocrine origin. Right nephrectomy was done and it turned out to be an insulin secreting neuroendocrine tumour. Neuroendocrine nature of this tumour was further confirmed by ultra-structural examination. Her hypoglycemia did not recur after resection of this tumour. CONCLUSION: Few cases of ectopic insulin secretion have been reported though some are not proven convincingly. This case addresses all the issues raised in previous case reports and proves by clinical, laboratory, functional imaging and immunohistochemical analysis that ectopic origin of insulin by non-pancreatic tumors does occur. To our knowledge, this is the first reported case of ectopic insulinoma arising from the kidney.

Necrolytic migratory erythema associated with glucagonoma syndrome diagnosed by 68Ga-DOTANOC PET-CT.

Necrolytic migratory erythema (NME) is a rare dermatological condition which presents a diagnostic challenge. Repeated negative skin biopsies and non-detection of any pancreatic tumor in conventional imaging modalities like a computed tomography (CT) scan and ultrasonogram (USG) make the diagnosis more difficult. By the time the diagnosis is made, the patient usually presents with metastasis. We present a rare case of difficult to diagnose NME, as repeated skin biopsies and conventional imaging modalities like CT and USG could not detect the underlying glucagonoma. A (68)Ga-DOTANOC positron emission tomography PET-CT was able to detect the underlying cause of NME as glucagonoma of the pancreas and the same investigation confirmed the absence of any metastasis elsewhere in the body. The tumor was excised and patient dramatically improved, and all skin lesions disappeared.

Lincoln's sign: where should we expect on 99mTc-MDP bone scintigraphy?

Classical appearance of "Lincoln's sign" on 99mTc-MDP bone scintigraphy has been described in literature in case of monostotic Paget disease of mandible showing increased radiotracer uptake in the body of mandible. This pattern has also been described as "black beard" sign. The monostotic presentation of Paget disease is rare, and involving the mandible, however, is very unusual. We present a case of carcinoma of the tongue with contiguous spread to the mandible presented in the similar fashion as the earlier reported Lincoln's sign or black beard sign on 99mTc-MDP bone scintigraphy. This appearance was confirmed with SPECT/CT, and the lytic sclerotic lesion of the mandible was confirmed.

Femoral-head vascularity after hip surface arthroplasty.

BACKGROUND: iatrogenic devascularization of the femoral head is as an area of concern following hip resurfacing arthroplasty, with probable implications on short-term failure and long-term survival of the implant. MATERIALS AND METHODS: we assessed the vascularity of 25 resurfaced femoral heads in 20 patients by comparison with preoperative and postoperative Tc-99m methylene diphosphonate (MDP) bone scintigraphy images, the postoperative scans being done 9 months after the surgery. RESULTS: eight out of 25 hips (32%) showed <55% of their preoperative uptake at a mean of 9 months after surgery and were categorized as showing reduced vascularity. CONCLUSION: our study reveals reduction in vascularity of the femoral-head remnant as a frequent occurrence after hip resurfacing. Our study also highlights the role of bone scintigraphy as tool in assessing the vascularity of resurfaced femoral heads.

Utility of Iodine-131 hybrid SPECT-CT fusion imaging before high-dose radioiodine therapy in papillary thyroid carcinoma.

The management protocol for differentiated thyroid cancer includes whole body iodine-131 imaging, to detect residual thyroid tissue and distant metastasis, after thyroidectomy. However, the diagnostic dose of radioiodine may fail to detect the non-functioning or poorly functioning metastasis. We present a case where hybrid single photon-emission computed tomographic and computed tomographic (SPECT-CT) fusion imaging, using a diagnostic dose of iodine-131, was able to detect both functioning as well as non-functioning pulmonary metastases, prior to high-dose radioiodine therapy.

FDG PET-CT in the management of primary breast lymphoma.

OBJECTIVE: Primary breast lymphoma (PBL) is a rare disease and its management differs from other breast cancers. The purpose of this study is to evaluate the role of FDG PET-CT in the management of PBL. We carried out 16 PET-CT scans and reviewed the literature. MATERIALS AND METHODS: A total of 16 FDG PET-CT scans were done in 8 female patients with PBL with a median age of 49 years (range: 27-68). Of the 16 PET-CT scans, 1 scan was done for primary diagnosis and staging (1 patient), 2 for staging (2 patients), 7 for evaluation of treatment response (6 patients), and 6 for detecting recurrence (4 patients). PET-CT image interpretation and analysis were performed qualitatively (visually) and semiquantitatively using standardized uptake value (SUV). Absence of uptake in the postchemotherapy follow-up PET-CT scan was considered as a complete response, and a fall of more than 50% of baseline SUV was considered as a significant response. RESULTS: One patient was successfully diagnosed to have PBL and staged using PET-CT. Two patients were correctly staged with the help of FDG PET-CT. Complete response was noted in all 6 patients (3 had a positive baseline scan and showed complete resolution of FDG uptake, the other 3 who did not have baseline PET-CT and lesions were detected on CT, and also showed complete resolution). Of the 4 patients evaluated for recurrence, 1 patient was positive and 3 patients were negative for recurrence in follow-up PET-CT scans done after 18, 22, and 24 months, respectively. CONCLUSION: FDG PET-CT has a definitive role in every step of management (diagnosis, staging, treatment response evaluation, and detection of recurrence) in patients with primary breast lymphoma.

Critical prospective appraisal of renal morphology and function in children undergoing shockwave lithotripsy and percutaneous nephrolithotomy.

PURPOSE: To assess the effect of shockwave lithotripsy (SWL) and percutaneous nephrolithotomy (PCNL) on renal morphology and function in children undergoing therapy for upper-tract urolithiasis. PATIENTS AND METHODS: Fourteen patients less than 13 years of age with renal or upper-ureteral calculi who were found suitable for primary SWL or PCNL were evaluated for alteration of renal morphology and function after treatment. Of the 18 renal units treated, SWL and PCNL were performed in 9 units each. The average stone size was 880.2 mm2 (range 110-3800 mm2; median 660 mm2). All children underwent ultrasonic estimation of renal length and parenchymal thickness, 99m technetium dimercaptosuccinic acid (DMSA) and 99m Tc-ethylene dicystine (EDC) scintigraphy, and glomerular filtration rate (GFR) estimation prior to intervention and at 3 and 6 months of follow-up. RESULTS: Extracorporeal lithotripsy achieved complete clearance in 8 renal units (88%), requiring an average of 6333 shockwaves and an average of 2.2 sessions per renal unit. The efficiency quotient was 42. Percutaneous surgery likewise achieved complete stone clearance in 88% of renal units, with three units requiring more than one tract. Mixed calcium oxalate monohydrate and dihydrate accounted for the majority of the stones. The mean preintervention GFR was 78.3 +/- 14.6 mL/min/1.73 m2 (median 82.5 mL/min/1.73 m2; range 54-98.6 mL/min/1.73 m2), whereas the mean GFR at 3 months was 78.95 +/- 14.4 mL/min/1.73 m2 (median 78.95 mL/min/1.73 m2; range 52-98 mL/min/1.73 m2). A marginal improvement of an average of 0.65 mL/min was noted. Split function EDC scans demonstrated improved drainage in five cases after intervention; the rest were unchanged. Preintervention DMSA scans revealed renal cortical scars in three children. None of the renal units had developed fresh scars at follow-up scans. None of the children developed new-onset hypertension, proteinuria, or alteration in renal size. CONCLUSION: In the present study, pediatric SWL and PCNL were not found to cause adverse renal morphologic or functional alteration. Stone clearance resulted in marginally improved function and better drainage.