Early onset absence epilepsy of childhood: Epidemiologic data, treatment and outcome in a sample of 56 patients born between 2000 and 2018.

PURPOSE: The aim of our work is to describe the characteristics of Early Onset Absence Epilepsy (EOAE) and to observe whether specific anamnestic, clinical or electroencephalographic characteristics can influence the drug sensitivity of this pathology. METHODS: We carried out a retrospective study of patients affected by absence epilepsy with onset under four years of age, born between January 1st 2000 and December 31st 2018, who were reffered to the Regional Epilepsy Center of Spedali Civili of Brescia. We then divided the sample into three groups based on the age of onset. RESULTS: Our sample is composed of 56 patients. Among the children with epilepsy onset under two years of age (11), all were still on therapy after three and six years of follow-up, and 64 % of them required polytherapy. Among patients with epilepsy onset between two and three years of age (24), 87 % were still on therapy after three years of follow-up and 68 % after six years of follow-up; 46 % of these subjects required polytherapy. Among patients with epilepsy onset between three and four years of age (21), 89 % were still on therapy after three years of follow-up and 38 % after six years of follow-up; 38 % of them required polytherapy. CONCLUSIONS: We observe that patients with an earlier epilepsy onset have a worse outcome and a lower drug sensitivity. This may allow to predict in which cases it would be appropriate to maintain antiseizure therapy for a prolonged period.

Diffusion-weighted imaging in hyperacute haemorrhagic stroke patients presenting within thrombolysis window.

INTRODUCTION: Diffusion-weighted imaging (DWI) in magnetic resonance imaging (MRI) has been proposed as the first line of neuroimaging for acute ischaemic stroke. The reliability of DWI in detecting intracranial haemorrhage, however, is still unproven, compared with susceptibility-weighted imaging (SWI) and CT scan which being considered the gold standard. This study seeks to establish the reliability of DWI as a first-line imaging modality to detect the intracranial haemorrhage in the patients present within the thrombolysis window. MATERIALS AND METHODS: A retrospective cross-sectional analysis was performed on patients who presented to our institution from April 2020 until July 2021 for acute stroke and had MRI brain as first-line neuroimaging. A total of 31 subjects were included in this study. Two radiologists assessed the signal patterns in DWI sequence and compared them with SWI and CT Brain, whenever available, as the gold standard for observing the presence of intracranial haemorrhage. RESULTS: The majority of patients with hyperacute bleed proven to be revealed on SWI or CT, thus showed characteristics of central hyperintensity and peripheral hypointense rim, on DWI. Slightly more than half (51.6%) presented with mild to moderate NIHSS scores (1-15). The sensitivity, specificity, positive predictive value and negative predictive value of DWI in detecting intracranial intra-axial haemorrhages were exceptionally high. There is strong interobserver level of agreement in identifying central haemorrhagic signal intensity [kappa = 0.94 (0.06), p < 0.05]. CONCLUSION: This study supported the DWI sequence as a reliable sequence in MRI, to detect intracranial haemorrhage in hyperacute stroke.

Accidental Nasal Myiasis Caused by Megaselia rufipes (Diptera: Phoridae) in a Child.

A case of a nasal myiasis in a 3-yr-old Italian girl who was referred to Bambino Gesù Hospital in Rome, Italy, is reported. Larvae discharged with the nasal mucus were microscopically identified as Megaselia spp.; DNA barcoding analysis showed that they belonged to the 'scuttle fly' species Megaselia rufipes (Meigen). Based on the patient's history, she became infected when she played outside. This is the first report of myiasis in humans due to M. rufipes (Diptera: Phoridae).

A clinical, histopathological and laboratory study of 19 consecutive Italian paediatric patients with chilblain-like lesions: lights and shadows on the relationship with COVID-19 infection.

BACKGROUND: Acral chilblain-like lesions are being increasingly reported during COVID-19 pandemic. However, only few patients proved positivity for SARS-CoV-2 infection. The relationship between this skin manifestation and COVID-19 infection has not been clarified yet. OBJECTIVE: To thoroughly characterize a prospective group of patients with chilblain-like lesions and to investigate the possible relationship with SARS-CoV-2 infection. METHODS: Following informed consent, patients underwent (i) clinical evaluation, (ii) RT-PCR and serology testing for SARS-CoV-2, (iii) digital videocapillaroscopy of finger and toe nailfolds, (iv) blood testing to screen for autoimmune diseases and coagulation anomalies, and (v) skin biopsy for histopathology, direct immunofluorescence and, in selected cases, electron microscopy. RESULTS: Nineteen patients, all adolescents (mean age: 14 years), were recruited. 11/19 (58%) of them and/or their cohabitants reported flu-like symptoms one to two months prior to skin manifestation onset. Lesions were localized to toes and also heels and soles. Videocapillaroscopy showed pericapillary oedema, dilated and abnormal capillaries, and microhaemorrhages both in finger and toe in the majority of patients. Major pathological findings included epidermal basal layer vacuolation, papillary dermis oedema and erythrocyte extravasation, perivascular and perieccrine dermal lymphocytic infiltrate, and mucin deposition in the dermis and hypodermis; dermal vessel thrombi were observed in two cases. Blood examinations were normal. Nasopharyngeal swab for SARS-CoV-2 and IgG serology for SARS-CoV-2 nucleocapsid protein were negative. Importantly, IgA serology for S1 domain of SARS-CoV-2 spike protein was positive in 6 patients and borderline in 3. CONCLUSIONS: Chilblain-like lesions during COVID-19 pandemic have specific epidemiologic, clinical, capillaroscopic and histopathological characteristics, which distinguish them from idiopathic perniosis. Though we could not formally prove SARS-CoV-2 infection in our patients, history data and the detection of anti-SARS-COV-2 IgA strongly suggest a relationship between skin lesions and COVID-19. Further investigations on the mechanisms of SARS-CoV-2 infection in children and pathogenesis of chilblain-like lesions are warranted.

Comparison of clinical, MRI and arthroscopic assessments of chronic ACL injuries, meniscal tears and cartilage defects.

PURPOSE: The aim of this study was to compare the accuracy of clinical examination to that of MRI evaluated by two independent radiologists for the diagnosis of meniscal tears and chronic anterior cruciate ligament injuries and to assess the MRI accuracy in the diagnosis of cartilage defects. METHODS: Seventy-six consecutive patients with suspected intra-articular knee pathology were prospectively evaluated by objective examination, 1.5 T MRI, re-examined by trained radiologist and arthroscopy. Accuracy, sensitivity, specificity, positive predictive value and negative predictive value were calculated. Agreement analysis with kappa (К) coefficient values was performed for meniscal and ACL tears. RESULTS: No differences were found between diagnostic accuracy of clinical examination, the first and second MRI reports in diagnosis of medial meniscus (84 vs 96 vs 97 %) and anterior cruciate ligament injuries (93 vs 78 vs 89 %). For the lateral meniscal tears, the accuracy of the second radiologist was significantly higher than those of the first (96 vs 75 %; p < 0.01) and clinical examination (96 vs 86 %; p = 0.02). High diagnostic values were obtained for the diagnosis of full-thickness chondral defects with sensitivity of 100 %, specificity of 95 % and accuracy of 95 %. CONCLUSION: Clinical and MRI evaluations have no differences in the diagnosis of medial meniscus and anterior cruciate ligament injuries. A trained radiologist obtained better sensitivity, specificity and accuracy in the diagnosis of lateral meniscus. 1.5 T MRI does not represent the technique of choice in the evaluation of chondral defect but demonstrated high diagnostic accuracy for detection of full-thickness chondral defects. LEVEL OF EVIDENCE: Diagnostic prospective study, Level II.

Onyx in Brain Arteriovenous Malformation Embolisation.

INTRODUCTION: Embolisation has long been used as an adjunct to surgical resection in the treatment of brain arteriovenous malformation (bAVM). The most commonly used embolic material, n-butylcyanoacrylate glue, requires experience and skill to handle its quick and unpredictable flow and polymerisation. A new liquid embolic agent, ethylene vinyl alcohol copolymer (Onyx), is less adhesive and polymerises slowly, which provides better control for radiologists performing embolisation. OBJECTIVE: To report our experience in embolisation using Onyx alone or in combination with histoacryl for bAVM embolisation in our tertiary referral centre. METHODS: We retrospectively reviewed the anatomy, technical conditions, complications and clinical outcome of all bAVM patients embolised at our centre using Onyx alone or in combination with n-butylcyanoacrylate glue. RESULTS: Between 2010 and 2013, 13 patients [6 (46.2%) male; 7 (53.8%) female; aged, 14-57 years] were included, and a total of 31 embolisations were performed. Clinical presentation included hemorrhage [9 (69.2%)], seizures [2 (15.4%)], and headache [2 (15.4%)]. Most AVMs were located in the brain hemispheres [12 (92.3%)] and measured <3 cm [7 (53.8%]. Complete occlusion of the AVM was obtained in 2 (15.4%) patients; 11 (84.6%) patients had partial occlusion [6 (54.5%) had <50% nidus occlusion]. Complications occurred in four procedures involving 3 patients (morbidity, 23.1%). This resulted in the death of 1 patient (mortality, 7.7%) and complete recovery with no disability in 2 patients. CONCLUSION: The total nidal occlusion achieved herein is comparable to other similar studies. Our morbidity and mortality were higher compared to other studies which may be attributed to the small number of patients. More data is being collected which may better reflect on our experience.

hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma.

BACKGROUND: hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking. METHODS: hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-Kras(G12D/+),LSL-Trp53(R175H/+) transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α-hERG1-MoAb. RESULTS: (i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α-hERG1-MoAb could detect PDAC in vivo. CONCLUSIONS: hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo.

A challenging alfa-fetoprotein in a cirrhotic patient.

A 57-year-old Italian man was admitted to our Hospital for investigation of a progressively raising alfa-fetoprotein (AFP) on the background of chronic hepatitis B infection. At abdominal imaging,liver morphology was suspected for advanced fibrosis but without any focal lesion. Clinical and ultrasonographic examinations were negative for testicular masses. When the patient was screened for gastroesophageal varices, upper intestinal endoscopy did not show signs of portal hypertension, while it revealed a gastric lesion which was histologically characterized as hepatoid adenocarcinoma of the stomach (HAS), with strong immunohistochemical positivity for AFP. The patient underwent subtotal gastrectomy and AFP fell within the normal range. This is a very rare case in which AFP-producing gastric cancer (AFPPGC), in the form of HAS, presented in a patient with chronic liver disease. Physicians should be particularly aware of AFPPGC when following patients with liver disorders due to the common use of AFP in this setting.

Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers.

BRAF(V600E) is the most frequent genetic mutation in papillary thyroid cancer (PTC) and has been reported as an independent predictor of poor prognosis of these patients. Current guidelines do not recommend the use of BRAF(V600E) mutational analysis on cytologic specimens from fine needle aspiration due to several reasons. Recently, immunohistochemistry using VE1, a mouse anti-human BRAF(V600E) antibody, has been reported as a highly reliable technique in detecting BRAF-mutated thyroid and nonthyroid cancers. The aim of this study was to test the reliability of VE1 immunohistochemistry on microhistologic samples from core needle biopsy (CNB) in identifying BRAF-mutated PTC. A series of 30 nodules (size ranging from 7 to 22 mm) from 30 patients who underwent surgery following CNB were included in the study. All these lesions had had inconclusive cytology. In all cases, both VE1 and BRAF(V600E) genotypes were evaluated. After surgery, final histology demonstrated 21 cancers and 9 benign lesions. CNB correctly diagnosed 20/20 PTC and 5/5 adenomatous nodules. One follicular thyroid cancer and 4 benign lesions were assessed at CNB as uncertain follicular neoplasm. VE1 immunohistochemistry revealed 8 mutated PTC and 22 negative cases. A 100% agreement was found when positive and negative VE1 results were compared with BRAF mutational status. These data are the first demonstration that VE1 immunohistochemistry performed on thyroid CNB samples perfectly matches with genetic analysis of BRAF status. Thus, VE1 antibody can be used on thyroid microhistologic specimens to detect BRAF(V600E)-mutated PTC before surgery.

Multimodality imaging of intraosseous ganglia of the wrist and their differential diagnosis.

Intraosseous ganglion (IOG) is the most frequently occurring bone lesion within the carpus and is often an incidental finding on radiographs obtained for other reasons. Two types of IOG have been described: an "idiopathic" form (or type I), the pathogenesis of which has not been completely clarified, and a "penetrating" form (or type II), caused by the intrusion of juxtacortical material (often a ganglion cyst of the dorsal soft tissue) into the cancellous bone compartment. The differential diagnosis for IOG is wide-ranging and complex, including lesions of posttraumatic (posttraumatic cystlike defects), degenerative (subchondral degenerative cysts), inflammatory [cystic rheumatoid arthritis, chronic tophaceous gout (CTG)], neoplastic (benign primary bone tumours and synovial proliferative lesions), ischaemic (Kienböck's disease or avascular osteonecrosis of the lunate) and metabolic (amyloidosis) origin. Multimodality imaging of IOGs is a useful diagnostic tool that provides complete morphological characterisation and differentiation from other intraosseous cystic abnormalities of the carpus. Thin-slice multidetector computed tomography (MDCT) can provide high-spatial-resolution images of the cortical and cancellous bone compartments, allowing detection of morphological findings helpful in characterising bone lesions, whereas magnetic resonance (MR) imaging can simultaneously visualise bone, articular surfaces, hyaline cartilage, fibrocartilage, capsules and ligaments, along with intra- and periarticular soft tissues.

Tuberculous meningoencephalitis in a patient with hairy cell leukemia in complete remission.

Tuberculous meningoencephalitis is a rare disease associated with high morbidity and mortality. We report a patient with hairy cell leukemia in complete remission who, after a single cycle of chemotherapy with cladribine, presented fever and neurological deficits. Laboratory diagnosis of tuberculous meningoencephalitis was made by polymerase chain reaction testing for Mycobacterium tuberculosis in cerebrospinal fluid. Despite the prompt institution of antitubercular-therapy, patient's general condition did not improve and he died. Mycobacterial infection should be considered in patients with intra-cranial lesions, affected by hematological malignancies and persistent immunosuppression.

[Multimodal imaging in the differential diagnosis of soft tissue calcinosis]. / Imaging multimodale nella diagnosi differenziale della calcinosi dei tessuti molli.

Soft tissue calcinosis is a common radiographic finding, which may be related to different types of pathological processes. Multimodality imaging, combined with analysis of clinical and laboratory data, plays an important role for the differential diagnosis of these conditions. Conventional radiography is considered the first line approach to soft tissue calcinosis; CT and MRI may provide further information to better characterize calcified deposits. Imaging may help to distinguish metabolic calcification, such as primary tumoral calcinosis and the secondary one (associated with acquired disorders of calcium or phosphate regulation), from dystrophic calcification, which is associated to normal blood values of phosphate. The sedimentation sign typical of tumoral calcinosis has been demonstrated by plain film radiography, CT, MRI, and, more recently, by ultrasonography. Other types of soft tissue calcinosis may have a degenerative, metaplastic or neoplastic origin, and their characterization strongly relies on multimodality imaging.

Human equilibrative nucleoside transporter 1 and carcinoma of the ampulla of Vater: expression differences in tumour histotypes.

The human equilibrative nucleoside transporter 1 (hENT1) is the major means by which gemcitabine enters human cells; recent evidence exists that hENT1 is expressed in carcinoma of the ampulla of Vater and that it should be considered as a molecular prognostic marker for patients with resected ampullary cancer. Aim of the present study is to evaluate the variations of hENT1 expression in ampullary carcinomas and to correlate such variations with histological subtypes and clinicopathological parameters. Forty-one ampullary carcinomas were histologically classified into intestinal, pancreaticobiliary and unusual types. hENT1 and Ki67 expression were evaluated by immunohistochemistry, and apoptotic cells were identified by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labelling (TUNEL) method. hENT1 overexpression was detected in 63.4% ampullary carcinomas. A significant difference in terms of hENT1 and Ki67 expression was found between intestinal vs. pancreaticobiliary types (P=0.03 and P=0.009 respectively). Moreover, a significant statistical positive correlation was found between apoptotic and proliferative Index (P=0.036), while no significant correlation was found between hENT1 and apoptosis. Our results on hENT1 expression suggest that classification of ampullary carcinoma by morphological subtypes may represent an additional tool in prospective clinical trials aimed at examining treatment efficacy; in addition, data obtained from Ki67 and TUNEL suggest a key role of hENT1 in tumour growth of ampullary carcinoma.

[Multimodality imaging of chronic tophaceous gout]. / Imaging integrato nella gotta cronica tofacea.

The diagnosis of gout is usually based on clinical presentation and laboratory findings. Imaging plays a role in the assessment and grading of articular damage related to chronic, long-standing disease, which is characterized by granulomatous synovitis, tophi, and erosions. Multimodality imaging of chronic tophaceous gout may be useful in clinical practice for a variety of purposes, including assessment of disease-related anatomical changes and monitoring of articular and soft-tissue lesions over time, especially in response to urate-lowering therapy. Radiography remains the primary imaging technique. Ultrasonography may detect monosodium urate crystals on cartilage, is helpful to assess small joint effusion, to guide to joint aspiration, and to evaluate the volume of tophi. Computed tomography is considered to be more sensitive than plain radiography in the detection and evaluation of cortical bone erosions associated with tophi. MRI represents the only imaging modality which provides visualization of bone marrow oedema associated with erosions and may be useful to characterize and distinguish tophi from other soft tissue nodules.

An unusual cause of blepharospasm.

We describe a rare case of multiple dilated Virchow-Robin spaces in the brainstem in a patient presenting initially with blepharospasm with subsequent spread to involve the face and neck. On magnetic resonance imaging (MRI), these lesions demonstrated an isointense signal to cerebrospinal fluid on all sequences with no mass effect or enhancement. Although rare, this condition should be considered part of the differential diagnosis when evaluating cystic abnormalities in the brainstem. This is the first reported case of blepharospasm with subsequent orofacial and neck dystonia caused by dilated Virchow-Robin spaces. The imaging findings and differential diagnoses are discussed.

High-resolution ultrasound anatomy of extrinsic carpal ligaments.

PURPOSE: Carpal ligaments can be classified as intrinsic and extrinsic. Extrinsic ligaments are often involved in carpal instability. The purpose of this article is to describe the sonographic appearance of extrinsic carpal ligaments on high-resolution ultrasound (HRUS) using magnetic resonance arthrography (MR arthrography) as a reference standard. MATERIALS AND METHODS: We studied both wrists in 18 healthy volunteers (ten men, eight women, age range 18-58 years, mean age 34 years) with a Philips iU22 US scanner equipped with a high-resolution linear-array broadband transducer (5-17 MHz). The scans were performed along the long axis of the extrinsic dorsal and ventral ligaments to assess their course, thickness and structure. Ten subjects were also studied with MR arthrography of the wrist. RESULTS: In all patients, the ligament components could be appreciated as thin fibrillar hyperechoic structures. The course of seven extrinsic carpal ligaments and their relationships with surrounding articular structures could be studied. The radioscapholunate and the ulnar collateral ligaments were not visible on US. MR arthrography depicted all ligaments except for the ulnar collateral, which was never visualised. CONCLUSIONS: The results obtained are consistent with those reported in the literature. HRUS provides good anatomical detail of the extrinsic carpal ligaments, but the role of US in planning the treatment of carpal instability disorders is yet to be demonstrated.

Outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is considered an optimal indication for liver transplantation (LT) because it may eliminate both the tumor and the underlying liver disease. The present study sought to compare cumulative survival, rate of HCC recurrence, and causes of death among patients with cirrhosis and HCC before and after the adoption of more restrictive criteria (Milan selection criteria) at the time of patient listing. Among 226 adult patients who received an elective liver transplantation between 1999 and 2005, 58 (27%) had a diagnosis of HCC at the time. The 38 patients who underwent transplantation for HCC in the period 1989 to 1998 were considered the "historical group." After LT (mean follow-up, 34 + 28 months), the cumulative survival rate was better among HCC versus non-HCC recipients (93% vs 71% at 1 year and 81% vs 67% at 3 years, respectively; P < .046), although the difference tended to attenuate after 5 years (66% vs 67%, respectively). Tumor recurrence (evaluated in patients surviving at least 3 months after LT) was observed in 10/31 in the historical group versus 4/53 among those who underwent transplantation after 1999. Among the causes of death, recurrence represented 50% in the old series and 23% in patients who underwent transplantation after 1999. Cumulative survival significantly improved among HCC patients who underwent transplantation after 1999 (93% vs 66% at 1 year and 81% vs 50% at 3 years; P < .00001). The 58 patients who underwent transplantation with a diagnosis of cirrhosis and concomitant HCC after 1999 showed even better survival than patients who underwent transplantation for end-stage liver disease without malignancy.

[Thin basement membrane and Alport syndrome]. / Membrana basale sottile: non sempre una diagnosi benigna.

Alport Syndrome (AS) is an inherited disorder of the glomerular basement membrane (GBM) transmitted as an X-linked dominant form in approximately 80% of patients. This X-linked form is caused by mutations in the collagen type IV alfa 5 gene (COL4A5) located on chromosome X; in the remainder of the cases, the autosomal, mostly recessive form, results from mutations in the collagen type IV alfa 3 gene (COL4A3) or alfa 4 gene (COL4A4) located on the 2q. Diagnostic lesions can be observed by electron microscopy (EM) and are characterized by thinning, thickening and/or splitting of the GBM. Isolated thinning of the GBM is usually associated with isolated microhematuria, a non progressive condition which has often a familial trait. Skin biopsy has also recently emerged to be a valuable alternative for the diagnosis of X-linked AS, because the alfa 5 (COL4A5) chain is also expressed in the epidermal basement membrane. A reliable diagnosis can often be achieved through combined renal and cutaneous immunohistochemical analysis, even in patients with limited clinical signs or atypical histological findings, and/or without suggestive family history. The present case report is an example of such diagnostic dilemma, where these techniques allowed to make a diagnosis despite contradictive clinical and histological features in contrast with a positive family history of renal disease.