Mariarosaria Cervasio

Typical progression of myoclonic epilepsy of the Lafora type: a case report

Background A 20-year-old woman presented to a specialist epilepsy center with a 3-year history of drug-resistant epileptic seizures, progressive myoclonus, ataxia, and cognitive decline.Investigations Neurological examination, neuropsychological testing, electrophysiological studies, skin biopsy, MRI, genetic testing, and autopsy.Diagnosis Lafora disease (EPM2), resulting from a homozygous missense mutation in EPM2B (NHLRC1; c205C>G; Pro69Ala).Management Symptomatic treatment with conventional antiepileptic and antimyoclonic drugs.

Hypomorphic NOTCH3 mutation in an Italian family with CADASIL features

The cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is because of NOTCH3 mutations affecting the number of cysteine residues. In this view, the role of atypical NOTCH3 mutations is still debated. Therefore, we investigated a family carrying a NOTCH3 nonsense mutation, with dominantly inherited recurrent cerebrovascular disorders. Among 7 family members, 4 received a clinical diagnosis of CADASIL. A heterozygous truncating mutation in exon 3 (c.307C>T, p.Arg103X) was found in the 4 clinically affected subjects and in one 27-year old lady, only complaining of migraine with aura. Magnetic resonance imaging scans found typical signs of small-vessel disease in the 4 affected subjects, supporting the clinical diagnosis. Skin biopsies did not show the typical granular osmiophilic material, but only nonspecific signs of vascular damage, resembling those previously described in Notch3 knockout mice. Interestingly, messenger RNA (mRNA) analysis supports the hypothesis of an atypical NOTCH3 mutation, suggesting a nonsense-mediated mRNA decay. In conclusion, the present study broadens the spectrum of CADASIL mutations, and, therefore, opens new insights about Notch3 signaling.

Melt-spun bioactive sutures containing nanohybrids for local delivery of anti-inflammatory drugs

In this work, a novel concept is introduced in drug-eluting fibres to ensure a good control of drug delivery features and wide applicability to different bioactive compounds. Composite bioactive sutures based on fibre grade poly(ε-caprolactone) (PCL) and loaded with the anti-inflammatory drug Diclofenac (Dic) or a Dic nanohybrid where the drug is intercalated in a synthetic hydrotalcite (Mg/Al hydroxycarbonate) (HT-Dic) were developed. Fibres were prepared by melt-spinning at different PCL/HT-Dic/Dic ratios and analysed in terms of morphology, mechanical properties and drug release features. Results emphasized that tensile properties of fibres are clearly affected by Dic or HT-Dic addition, while the presence of knots has limited influence on the mechanical behaviour of the sutures. Release of Dic strongly depends on how Dic is loaded in the fibre (as free or nanohybrid) whereas the combination of free Dic and HT-Dic can allow a further tuning of release profile. In vivo experiments show a reduction of inflammatory responses associated with Dic-loaded fibers. Thus, a proof of principle is provided for a novel class of bioactive sutures integrating advanced controlled-release technologies.

A case of pure uterine lipoma: immunohistochemical and ultrastructural focus

BackgroundPure uterine lipoma is a rare clinical event and only a few cases have been reported in literature. The histogenesis of these lesions is still debatable. Preoperative diagnosis is difficult and should be pathologically confirmed postoperatively.CaseWe report the case of a 58-year-old woman who presented with pelvic pain and postmenopausal uterine bleeding. The hysterectomy specimen showed a pure intramural lipoma of the uterus. An immunohistochemical study revealed that the lipomatous tissue was reactive to S-100, vimentin, actin and desmin. Electron microscopy examination revealed bundles of spindle cells with intracytoplasmatic vacuoles and parallel-arranged intermediate filaments in the surrounding zone, in which adipose cells were mixed with muscular cells.DiscussionClinical and histological diagnosis of pure uterine lipomas are described and a possible involvement of fatty metaplasia of smooth muscle cells in the development of pure uterine lipomas is discussed.

White matter involvement in a family with a novel PDGFB mutation

Primary familial brain calcification (PFBC) (formerly idiopathic basal ganglia calcification; Fahr disease) is an autosomal dominant cerebral microvascular calcifying disorder with variable clinical and imaging features.1 Four causative genes have been identified: SLC20A2,2 PDGFRB,3 PDGFB,4 and XPR1.5

22-year-old girl with status epilepticus and progressive neurological symptoms.

A 22-year-old girl presented with convulsive status epilepticus and a previous history of recurrent seizures, myoclonus, ataxia and impaired cognitive functions. Neurological examination revealed rest and action-induced myoclonus, pyramidal signs and opposition hypertonia. Testing revealed severe metabolic acidosis, elevated transaminases and creatine kinase, and respiratory insufficiency. After intubation and ventilation, thiopental was introduced but the patients condition worsened dramatically with death in a few hours. Autopsy showed profuse periodic acid-Schiff (PAS) positive intracellular inclusions in the CNS (Lafora bodies), most abundant in thalamus, cerebellum, and brainstem, as well as in other organs. Genetic testing revealed a homozygous missense mutation (c.205C > G, P69A) in the EPM2B (NHLRC1) gene, confirming the diagnosis of progressive myoclonic epilepsy Lafora-type.

Essential role of ultrastructural examination for spindle cell oncocytoma: Case report of a rare neoplasm and review of the literature

ABSTRACT Spindle cell oncocytoma (SCO) is an extremely rare neoplasm of the sellar region recognized as a distinct benign histopathological subtype of pituitary tumors in the 2007 World Health Organization classification of tumors of the central nervous system. The morphology of its neoplastic cells (spindle cells and granular eosinophilic cytoplasm) is common to several other lesions so that immunohistochemistry, together with ultrastructural examination, becomes essential in solving this differential diagnosis. Despite being labeled as benign, recurrence is described. Herein, we report a case of SCO in a 77-year-old man and discuss the diagnostic difficulties, ultrastructural aspects, and prognostic factors.

Comparison of Left Ventricular Myocardial Structure and Function in Patients with Aortic Stenosis and Those with Pure Aortic Regurgitation

Objective: We aimed to support the structural and functional distinction between aortic stenosis (AS) and aortic regurgitation (AR). Methods: Biopsy specimens taken from 70 selected patients (35 with AS and 35 with AR) undergoing aortic valve replacement (AVR) were analyzed for their cardiomyocyte dimensions and structure, interstitial fibrosis and contractile function. To determine normal values of contractile function, 10 donor hearts were analyzed. Results: Cardiomyocyte diameter was higher in AS than in AR (22.7 ± 2.2 vs. 13.2 ± 0.7 µm, p < 0.001). Length was higher in AR (121.2 ± 9.4 vs. 95.6 ± 3.7 µm, p < 0.001). Collagen volume fraction was increased in both AS and AR, but was lower in the AS specimens (7.7 ± 2.3 vs. 8.9 ± 2.3, p = 0.01). Myofibril density was reduced in AR (38 ± 4 vs. 48 ± 5%, p < 0.001). Cardiomyocyte diameter and length were closely linked to the relative left ventricular (LV) wall thickness (R2 = 0.85, p < 0.001 and R2 = 0.68, p = 0.003). The cardiomyocytes of AS patients had higher Fpassive (6.6 ± 0.3 vs. 4.6 ± 0.2 kN/m2, p < 0.001), but their total force was comparable. Fpassive was also significantly higher in AS patients with restrictive rather than pseudo-normal LV filling (7.3 ± 0.5 vs. 6.7 ± 0.6, p = 0.004). In AS patients, but not in AR patients, Fpassive showed a significant association with the cardiomyocyte diameter (R2 = 0.88, p < 0.001 vs. R2 = 0.31, p = 0.6). Conclusions: LV myocardial structure and function differ in AS and AR, allowing for compensative adjustment of the diastolic/systolic properties of the myocardium.

A 53-Year-Old Woman with a Subfascial Mass of the Back that Lasted for Years

A 53-year-old woman presented with a growing mass in the left lumbar region. The patient had become casually aware of it 10 years ago. Since then she performed radiological and clinical follow-up; she refused surgical resection. In 2009, a cytological examination had displayed mesenchymal cells without nuclear atypia. In the last year, the tumor had been growing and had become symptomatic with pain during physical activity. Clinical examination revealed an unmovable swelling on the left lumbar region with intact skin. MRI showed a 9 3 435 cm T1 hypointense and T2 hyperintense mass, with a strong and heterogeneous enhancement after contrast infusion and a hypointense central core. It extended from the body of the second to the fifth lumbar vertebra. CT scan of the chest also revealed four pulmonary nodules enhancing with contrast, two of which were hypermetabolic during the whole-body PET-CT scan (max SUV 2.7 and 2.4). The patient underwent surgical resection of the lumbar lesion which was easily removed with sharp dissection from the surrounding muscle fibers. PATHOLOGICAL FINDINGS

A Granulomatous Hypophysitis "Consequent" to a Silent ACTH Cell Adenoma: A Case Report

Herein is described a rare association of granulomatous hypophysitis and a silent corticotroph macroadenoma, observed in a 50year-old male who came to the attention of the clinicians with a history of frontal headache. Silent adenomas account for about one quarter of the pituitary adenomas and are characterized by the lack of a characteristic clinical syndrome or serum hormone marker. A granulomatous pituitary inflammatory reaction can be caused by systemic tuberculosis, syphilis, fungal infections or be idiopathic. The coincidence of these two conditions is known in the literature and a few hypotheses have been advanced concerning their relationship. The aim of our report was to scrutinize any possibility of causality that could explain this phenomenon. The ultimate goal was trying to understand a possible prognostic significance of the inflammatory reaction to neoplastic proliferation if there were any.