Pearls & Oy-sters: Thyroid-Associated Ophthalmopathy and Transient Neuromuscular Junction Disorder Due to Graves Disease.

The concomitant presentation of thyroid-associated ophthalmopathy (TAO) and ocular myasthenia gravis is well documented. In the course of Graves disease (GD), symptomatic transient neuromuscular junction disorder may occur due to the effect of thyroid hormones at the neuromuscular synapse. Diagnostic clues are the clinical and electrophysiologic remission synchronous with restoration of euthyroidism. Furthermore, the occurrence of thymic hyperplasia in GD poses further diagnostic and therapeutic considerations. These points are discussed in the case report of a 43-year-old male patient suffering from TAO and transient neuromuscular junction disorder due to GD.

Transorbital sonography in idiopathic intracranial hypertension: Single-center study, systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Transorbital sonography (TOS) provides a noninvasive tool to detect intracranial pressure by assessing optic nerve sheath diameter (ONSD) and optic disc elevation (ODE). The utility of TOS in the diagnosis of idiopathic intracranial hypertension (IIH) has been increasingly recognized. METHODS: A single-center case-control study sought to compare TOS-acquired ONSD and ODE among IIH-cases versus patients with other neurological diseases (controls). Furthermore, a systematic review and meta-analysis was conducted to present pooled mean differences and diagnostic measures of ONSD and ODE between IIH-cases and controls. RESULTS: In the single-center study, consisting of 31 IIH-cases and 34 sex- and age-matched controls, ONSD values were higher among IIH-cases than controls (p<.001), while ODE was more prevalent in cases (65% vs. 15%; p<.001). The receiver-operating characteristic (ROC)-curve analysis revealed that the optimal cutoff value of ONSD for predicting IIH was 5.15 mm, with an area under the curve (AUC) of 0.914 (95% confidence interval [CI]: 0.861-0.967) and sensitivity and specificity values of 85% and 90%, respectively. In a meta-analysis of 14 included studies with 415 IIH-cases, ONSD and ODE values were higher in IIH-cases than controls (mean difference in ONSD 1.20 mm; 95% CI: 0.96-1.44 mm and in ODE 0.3 mm; 95% CI: 0.33-0.67 mm). With regard to ONSD, pooled sensitivity, specificity, and diagnostic odds ratio were calculated at 85.5% (95% CI: 77.9-90.8%), 90.7% (95% CI: 84.6-94.5%), and 57.394 (95% CI: 24.597-133.924), respectively. The AUC in summary ROC-curve analysis was 0.878 (95% CI: 0.858-0.899) with an optimal cutoff point of 5.0 mm. CONCLUSIONS: TOS has a high diagnostic utility for the noninvasive diagnosis of IIH and may deserve wider implementation in everyday clinical practice.

Double Trouble: Association of Malignant Melanoma with Sporadic and Genetic Forms of Parkinson's Disease and Asymptomatic Carriers of Related Genes: A Brief Report.

Introduction: Previous epidemiological evidence has established the co-occurrence of malignant melanoma (MM) and Parkinson's disease (PD). Shared molecular mechanisms have been proposed to be implicated in this relationship. The aim of the present study was to assess the prevalence of MM in patients with sporadic and genetic types of PD, as well as in asymptomatic carriers of PD-related genes. Methods: Data regarding past medical history and concomitant disease of 1416 patients with PD (including 20 participants with prodromal disease who phenoconverted to PD), 275 healthy controls (HCs) and 670 asymptomatic carriers of PD-related genes were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on information about a medical record of MM. We also retrieved data regarding the genetic status of selected PPMI participants with a positive MM history. Results: In total, 46 patients with PD reported a positive MM history. Concerning the genetic forms of PD, nine of these PD patients (2.47%) carried a Leucine Rich Repeat Kinase 2 (LRRK2) gene mutation (mainly the G2019S), while eight (4.49%) harbored a Glucocerebrosidase (GBA) gene mutation (mainly the N370S). No alpha-synuclein (SNCA) gene mutation was identified in patients with an MM history. The remaining 29 PD patients (3.5%) were genetically undetermined. In total, 18 asymptomatic carriers of PD-related genes had a positive medical history for MM: among them, 10 carried an LRRK2 gene mutation (2.69%) and 10 a GBA gene mutation (3.51%) (2 were dual carriers). MM history was identified for seven HCs (2.5%). Conclusions: We replicated the previously reported association between genetically undetermined PD (GU-PD) and MM. A correlation of LRRK2 mutations with the development of MM could not be verified in either symptomatic PD patients or asymptomatic carriers, implicating distinct pathogenetic mechanisms as compared to GU-PD. Importantly, despite the limited literature evidence on Gaucher disease, this study highlights for the first time the relatively high prevalence of MM among asymptomatic and symptomatic PD GBA mutation carriers, with potential clinical implications.

Intradiscal Gelified Ethanol Nucleolysis versus Endoscopic Surgery for Lumbar Disc Herniation Radiculopathy.

The purpose of this study was to retrospectively compare efficacy and safety between intradiscal injection of a gelified ethanol product and tubular discectomy in the treatment of intervertebral disk herniation. A bi-central institutional database research identified forty (40) patients suffering from symptomatic contained disc herniation. Nucleolysis Group included 20 patients [mean 50.05 ± 9.27 years-of-age (male/female 14/6-70/30%)] and Surgery Group included 20 patients [mean 48.45 ± 14.53 years-of-age, (male/female 12/8-60/40%)]. Primary outcome was overall 12-month improvement over baseline in leg pain (NVS units). Procedural technical outcomes were recorded, and adverse events were evaluated at all follow-up intervals. CIRSE classification system was used for complications' reporting. Mean pre-operative pain score in Nucleolysis Group was 7.95 ± 0.94 reduced to 1.25 ± 1.11 at month 1 and 0.45 ± 0.75 NVS units at year 1. Mean pre-operative pain score in Surgery Group was 7.65 ± 1.13 reduced to 1.55 ± 1.79 at month 1 and 0.70 ± 1.38 NVS units at year 1. Pain decrease was statistically significant after both procedures (p < 0.001). There was no statistically significant difference between pain reduction in both groups (p = 0.347). The decrease differences of the pain effect upon general activities, sleeping, socializing, walking, and enjoying life in the follow-up period between the two groups were not statistically significant. No complications were noted in both groups. Results from the current study report that intradiscal injection of a gelified ethanol and tubular discectomy were equally effective on terms of efficacy and safety for the treatment of symptomatic lumbar intervertebral disc herniation regarding the 12-month mean leg pain improvement. Both achieved similar rapid significant clinical improvement persisting throughout follow-up period.

Computed tomography-guided percutaneous microwave ablation for renal cell carcinoma: evaluating the performance of nephrometry scores.

OBJECTIVES: The purpose of the current study is to evaluate the performance of RENAL and mRENAL scores, in the prediction of oncological outcomes in patients treated with microwave ablation (MWA) for (T1) renal cell carcinomas (RCC). METHODS: Institutional database retrospective research identified 76 patients with a biopsy-proven solitary T1a (84%) or T1b (16%) RCC; all patients underwent CT-guided MWA ablation. Tumor complexity was reviewed by calculating RENAL and mRENAL scores. RESULTS: The majority of the lesions were exophytic (82.9%), with > 7 mm nearness to the collecting system (53.9%), located posteriorly (73.6%), and lower to polar lines (61.8%). Mean RENAL and mRENAL scores were 5.7 (SD = 1.9) and 6.1 (SD = 2.1) respectively. Progression rates were significantly higher with greater tumor size (> 4 cm), with < 4 mm nearness to the collecting system, for tumors crossing a polar line and with the anterior location. None of the above was associated with complications. RENAL and mRENAL scores were significantly higher in patients with incomplete ablation. The ROC analysis showed the significant prognostic ability of both RENAL and mRENAL scores for progression. In both scores, the optimal cut-off point was 6.5. Univariate Cox regression analysis for progression showed a hazard ratio of 7.73 for the RENAL score and 7.48 for the mRENAL score. CONCLUSION: The results of the present study show that the risk of progression was higher in patients with RENAL and mRENAL score of > 6.5, in T1b tumors, close to the collective system (< 4 mm), crossing polar lines and anterior location. CLINICAL RELEVANCE STATEMENT: CT-guided percutaneous MWA is a safe and effective technique for the treatment of T1a renal cell carcinomas. Different morphometric parameters of RCC tumors including RENAL and mRENAL score > 6.5, size, proximity to the collecting system, and crossing of polar lines impact the efficacy of MWA and progression survival rates. KEY POINTS: • The risk of progression is higher in patients with RENAL and mRENAL score > 6.5, in T1b tumors, close to the collective system (< 4 mm), crossing polar lines and anterior location. • The significant prognostic ability of the mRENAL score for progression was higher than the respective of the RENAL score. • Complications were not associated with any of the above factors.

Ablative Techniques for Sarcoma Metastatic Disease: Current Role and Clinical Applications.

Sarcomas are heterogenous mesenchymal neoplasms with more than 80 different histologic subtypes. Lung followed by liver and bone are the most common sites of sarcoma metastatic disease. Ablative techniques have been recently added as an additional alternative curative or palliative therapeutic tool in sarcoma metastatic disease. When compared to surgery, ablative techniques are less invasive therapies which can be performed even in non-surgical candidates and are related to decreased recovery time as well as preservation of the treated organ's long-term function. Literature data upon ablative techniques for sarcoma metastatic disease are quite heterogeneous and variable regarding the size and the number of the treated lesions and the different histologic subtypes of the original soft tissue or bone sarcoma. The present study focuses upon the current role of minimal invasive thermal ablative techniques for the management of metastatic sarcoma disease. The purpose of this review is to present the current minimally invasive ablative techniques in the treatment of metastatic soft tissue and bone sarcoma, including local control and survival rates.

Multiple Sclerosis and MEN2 Neoplasia in a Female Patient: A Unique Co-Existence with Expanded Immunological Interest and Therapeutical Challenges, before and after Patient's COVID-19 Infection.

Multiple sclerosis (MS) and its various comorbidities that may be observed are of great interest due to the complexity of MS pathophysiology and all of the immunological changes that follow. The incidence of cancer in MS has been investigated for several years, as not only does it affect ongoing therapeutical decisions, but also, certain disease-modifying treatments (DMTs) may increase the risk of tumorigenesis. For the first time, we present a case of a female patient with pediatric-onset MS (POMS) and multiple endocrine neoplasia 2B (MEN2B) and analyze the immunological impact of these diseases on the therapeutical choice, under the umbrella of her COVID-19 infection and the SARS-CoV-2 pandemic as a whole. We also review the existing literature regarding the immunogenetic and immunological correlations between these two extremely rare diseases and discuss the most suitable treatment for our case, which seems to be an anti-CD20 agent due to a better outcome in putative MS worsening and tumor progression, when killer immunoglobulin-like receptors' (KIR) expression is reduced in natural killer (NK) cells. We also broaden our concerns on this comorbidity issue, at the same time focusing on the future research needed in this unexplored field of the comorbidity of MS and cancers.

Percutaneous Navigation under Local Anesthesia for Computed Tomography-Guided Microwave Ablation of Malignant Liver Lesions Located in the Hepatic Dome.

Background and Objectives: The aim of the present study was to report the safety and efficacy of percutaneous navigation under local anesthesia for computed tomography-guided microwave ablation of malignant liver lesions located in the hepatic dome. Patients with primary and secondary malignant liver lesions located in the hepatic dome who underwent percutaneous computed tomography-guided microwave ablation using a computer-assisted navigation system under local anesthesia were prospectively evaluated. The primary objective was technical success. Materials and Methods: The sample consisted of 10 participants (16 lesions) with a mean age of 60.60 years (SD = 9.25 years) and a mean size of 20.37 ± 7.29 cm, and the mean follow-up time was 3.4 months (SD = 1.41) months. Results: Primary technical success was 93.75%. Tumor remnant was noticed at one month follow-up in a single metastatic lesion, which was re-treated with an ablation session, and no tumor remnant was depicted in the subsequent imaging follow-up (secondary technical success 100%). Grade I self-limited complications (according to the CIRSE classification system) included small pleural effusion (n = 1) and minor bleeding post antenna removal (n = 1) requiring nothing but observation. Conclusions: the findings of the present study indicate that percutaneous navigation under local anesthesia is a safe and efficacious approach for computed tomography-guided microwave ablation of malignant liver lesions located in the hepatic dome. Large randomized controlled studies are warranted to observe treatment effectiveness and compare the results with those of other options.

MRI evidence of extraocular muscle atrophy and fatty replacement in myasthenia gravis.

PURPOSE: The aim of the study was to evaluate extraocular muscle (EOM) atrophy and fatty replacement in ocular myasthenia gravis (OMG) and generalized myasthenia gravis (GMG) patients with chronic and untreated ocular symptoms or with inadequate response to immunotherapy and unprovoked ocular exacerbations despite chronic immunotherapy. METHODS: Nineteen patients with either OMG or GMG and 19 healthy age-matched controls underwent an orbital MRI. Visually obvious muscle atrophy and muscle fatty replacement were evaluated by two raters independently. Maximum thickness of EOM was measured. Measurements of the muscles of each participant were added up, in order to calculate the total thickness. RESULTS: Eleven patients suffered from AChR-positive GMG, and 8 patients from OMG. All patients had chronic ocular symptoms or inadequate response to corticosteroids and unprovoked ocular exacerbations in spite of immunotherapy. Fatty replacement was reported in 6/19 (31.6%) patients and 0/19 (0%) controls (p = 0.02). Obvious atrophy in at least one muscle was reported in 8/19 (42.1%) patients and 1/19 (5.3%) controls (p = 0.019). Statistically significant differences between the two groups were also found in the mean total thickness, as well as in the thickness of superior recti, levator palpebrae, inferior recti, and superior oblique muscles. CONCLUSION: EOM atrophy and fatty replacement were seen frequently in our series of MG patients with treatment difficulties and frequent relapses of ocular involvement.

Percutaneous Microwave Ablation of Liver Lesions: Differences on the Sphericity Index of the Ablation Zone between Cirrhotic and Healthy Liver Parenchyma.

To compare different parameters of the sphericity index of the ablation zone following microwave ablation (MWA) on cirrhotic- and healthy-liver parenchyma in a series of patients treated with the same MWA system. Institutional database research identified 46 patients (77 lesions) who underwent MWA. "Cirrhotic liver group" (CLG) included 35 hepatocellular carcinoma lesions; "healthy liver group" (HLG) included 42 metastatic lesions. The long axis (LAD), short axis 1 (SAD-1) and 2 (SAD-2), the mean SAD-1 and SAD-2 (mSAD) diameter (in mm) and the mean sphericity (mSPH) index of the ablation zones were evaluated for each treated lesion in both groups from baseline to follow-up. A mixed model analysis of variance reported significant main effect of group on SAD-1 (p = 0.023), SAD-2 (p = 0.010) and mSAD (p = 0.010), with HLG showing lower values compared to CLG. No differences were detected on the LAD (pFDR = 0.089; d = 0.45), and mSPH (pFDR = 0.148, d = 0.40) between the two groups. However, a significant main effect of time was found on LAD (p < 0.001), SAD-1 (p < 0.001), SAD-2 (p < 0.001) and mSAD (p < 0.001), with decreased values in all indices at follow-up compared to baseline. A significant group by time interaction was observed on mSPH (p = 0.044); HLG had significantly lower mSPH at follow-up where CLG did not show any significant change. Our findings indicate that although in cirrhotic liver short axis diameter of the MWA zone seems to be significantly longer, this has no effect on the sphericity index which showed no significant difference between cirrhotic vs. healthy liver lesions. On the contrary, on one month follow-up ablation zones tend to become significant more ellipsoid in healthy whilst remains stable in cirrhotic liver.

The Role of Percutaneous Ablation in the Management of Colorectal Cancer Liver Metastatic Disease.

Approximately 50% of colorectal cancer patients will develop metastases during the course of the disease. Local or locoregional therapies for the treatment of liver metastases are used in the management of oligometastatic colorectal liver disease, especially in nonsurgical candidates. Thermal ablation (TA) is recommended in the treatment of limited liver metastases as free-standing therapy or in combination with surgery as long as all visible disease can be eradicated. Percutaneous TA has been proven as a safe and efficacious therapy offering sustained local tumor control and improved patient survival. Continuous technological advances in diagnostic imaging and guidance tools, the evolution of devices allowing for optimization of ablation parameters, as well as the ability to perform margin assessment have improved the efficacy of ablation. This allows resectable small volume diseases to be cured with percutaneous ablation. The ongoing detailed information and increasing understanding of tumor biology, genetics, and tissue biomarkers that impact oncologic outcomes as well as their implications on the results of ablation have further allowed for treatment customization and improved oncologic outcomes even in those with more aggressive tumor biology. The purpose of this review is to present the most common indications for image-guided percutaneous ablation in colorectal cancer liver metastases, to describe technical considerations, and to discuss relevant peer-reviewed evidence on this topic. The growing role of imaging and image-guidance as well as controversies regarding several devices are addressed.

Recurrent Fulminant Tumefactive Demyelination With Marburg-Like Features and Atypical Presentation: Therapeutic Dilemmas and Review of Literature.

Atypical forms of demyelinating diseases with tumor-like lesions and aggressive course represent a diagnostic and therapeutic challenge for neurologists. Herein, we describe a 50-year-old woman presenting with subacute onset of left hemiparesis, memory difficulties and headache. Brain MRI revealed a tumefactive right frontal-parietal lesion with perilesional edema, mass effect and homogenous post-contrast enhancement, along with other small atypical lesions in the white-matter. Brain biopsy of cerebral lesion ruled out lymphoma or any other neoplastic process and patient placed on corticosteroids with complete clinical/radiological remission. Two years after disease initiation, there was disease exacerbation with reappearance of the tumor-like mass. The patient initially responded to high doses of corticosteroids but soon became resistant. Plasma-exchange sessions were not able to limit disease burden. Resistance to therapeutic efforts led to a second biopsy that showed perivascular demyelination, predominantly consisting of macrophages, with a small number of T and B lymphocytes, and the presence of reactive astrocytes, typical of Creutzfeldt-Peters cells. The patient received high doses of cyclophosphamide with substantial clinical/radiological response but relapsed after 7-intensive cycles. She received 4-weekly doses of rituximab with disease exacerbation and brainstem involvement. She eventually died with complicated pneumonia. We present a very rare case of recurrent tumefactive demyelinating lesions, with atypical tumor-like characteristics, with initial response to corticosteroids and cyclophosphamide, but subsequent development of drug-resistance and unexpected exacerbation upon rituximab administration. Our clinical case raises therapeutic dilemmas and points to the need for immediate and appropriate immunosuppression in difficult to treat tumefactive CNS lesions with Marburg-like features.

Recurrent myelitis and asymptomatic hypophysitis in IgG4-related disease: case-based review.

IgG4-related disease (IgG4-RD) is a disorder with various clinical manifestations. Central nervous system (CNS) involvement is well recognized, with hypertrophic pachymeningitis and hypophysitis being the most common manifestations. Spinal cord involvement is an extremely rare manifestation. We present the first case of an IgG4-RD patient with spinal cord parenchymal disease and concurrent hypophysitis. We review also the current literature about CNS parenchymal involvement in the context of IgG4-RD. A young female presented with clinical symptoms of myelitis. Cervical spinal cord magnetic resonance imaging (MRI) displayed features of longitudinally extensive transverse myelitis (LETM). Brain MRI showed a small number of high-intensity lesions in the deep white matter and enlargement of hypophysis with homogeneous gadolinium enhancement (asymptomatic hypophysitis). Diagnostic workup revealed elevated IgG4 serum levels (146 mg/dL). Our patient fulfilled the organ-specific diagnostic criteria of IgG4-hypophysitis. Treatment with intravenous glucocorticoids led to rapid clinical response, and to the substantial resolution of imaging findings. Azathioprine was used as a maintenance treatment. One relapse occurred 2 years after the initial diagnosis and patient was re-treated with glucocorticoids. Three years after relapse, patient is in remission with azathioprine. We present the first case of myelitis with radiological features of LETM associated with increased IgG4 serum levels and the simultaneous presence of asymptomatic IgG4-related hypophysitis.

Ocular flutter as presenting manifestation of pediatric MOG antibody-associated demyelination: A case report.

A 13-year-old girl presented with a 5-day history of oscillopsia. On examination, ocular flutter and mild cerebellar signs were found. Brain magnetic resonance imaging (MRI) revealed four periventricular and subcortical non-enhancing lesions. Cerebrospinal fluid (CSF) oligoclonal bands were negative. Neuroblastoma or other malignancies were not found. She responded well to a corticosteroid-intravenous immunoglobulin (IVIG) combination and remained symptom-free for 3 years until presenting again with isolated ocular flutter. Brain MRI at this time remained atypical for classic multiple sclerosis (MS) with a predominance of juxtacortical demyelinating lesions. CSF was positive for oligoclonal bands. Serum myelin oligodendrocyte glycoprotein (MOG) antibodies were present. Ocular flutter can be the presenting feature of MOG antibody-associated pediatric demyelination.