Neuropsychiatric syndrome with myoclonus after SARS-CoV-2 infection in a paediatric patient.

We report the case of a 12-years-old patient who subacutely developed a positive and negative myoclonus of limbs and face, drowsiness and memory deficits after getting infected by SARS-CoV-2. On admission, nasopharyngeal swab for SARS-CoV-2, brain and spinal MRI with and without contrast, EEG, chest X-ray and abdominal ultrasound were negative. CSF physical-chemical examination, culture, PCR testing for SARS-CoV-2 and other pathogens, and oligoclonal IgG bands were negative as well. A full panel blood test, including clotting, autoimmunity and paraneoplastic blood studies, did not show any alteration. The neuropsychological examination showed an impairment in memory, visual-motor coordination, inductive reasoning skills, attention, and concentration. The patient was first treated with clonazepam and then with intravenous methylprednisolone for five days, with poor response. For this reason, he then received a cycle of IVIG, thus reaching a gradual and complete recovery. To date, this is the first case of a COVID-19 associated myoclonus affecting a paediatric patient.

Default mode network changes in multiple sclerosis: a link between depression and cognitive impairment?

BACKGROUND AND PURPOSE: In multiple sclerosis (MS), depression is a common disorder whose pathophysiology is still debated. To gain insights into the pathophysiology of depression in MS, resting-state (RS) functional connectivity (FC) changes of the default mode network (DMN), salience network (SN) and executive control network (ECN) were assessed in a group of depressed MS (D-MS) patients and in appropriately matched control groups. METHODS: Sixteen D-MS patients, 17 non-depressed MS (ND-MS) patients, 17 non-depressed healthy controls and 15 depressed subjects (D-S), age, sex and education matched, cognitively preserved and non-fatigued, were enrolled. All participants underwent a neuropsychological evaluation and RS functional magnetic resonance imaging study. RESULTS: Comparing D-MS patients with D-S, within the DMN, a significant RS-FC suppression was found in the posterior cingulate cortex (PCC); comparing D-MS with ND-MS, FC was significantly increased in the anterior cingulate cortex and significantly reduced in the PCC. Within the SN increased FC in the right supramarginal gyrus and right middle frontal gyrus was found in D-MS patients compared to D-S and to ND-MS; within the ECN increased FC in the right inferior parietal cortex was found in D-MS patients compared to ND-MS patients. CONCLUSIONS: In cognitively preserved D-MS patients, FC derangement occurs in the SN, ECN and DMN. In the latter, changes occurring both in the anterior cingulate cortex and PCC suggest that depression in MS may be linked to MS itself and, in particular, to a peculiar pattern of network abnormalities favored by MS pathology through disconnection mechanisms. Reduced FC in the PCC, similar to MS patients with cognitive impairment, suggests a functional link between depression and cognitive impairment in MS.

Cognitive impairment and memory disorders in relapsing-remitting multiple sclerosis: the role of white matter, gray matter and hippocampus.

Cognitive disorders occur in up to 65 % of multiple sclerosis (MS) patients; they have been correlated with different MRI measures of brain tissue damage, whole and regional brain atrophy. The hippocampal involvement has been poorly investigated in cognitively impaired (CI) MS patients. The objective of this study is to analyze and compare brain tissue abnormalities, including hippocampal atrophy, in relapsing-remitting MS (RRMS) patients with and without cognitive deficits, and to investigate their role in determining cognitive impairment in MS. Forty-six RRMS patients [20 CI and 26 cognitively preserved (CP)] and 25 age, sex and education-matched healthy controls (HCs) underwent neuropsychological evaluation and 3-Tesla anatomical MRI. T2 lesion load (T2-LL) was computed with a semiautomatic method, gray matter volume and white matter volume were estimated using SIENAX. Hippocampal volume (HV) was obtained by manual segmentation. Brain tissues volumes were compared among groups and correlated with cognitive performances. Compared to HCs, RRMS patients had significant atrophy of WM, GM, left and right Hippocampus (p < 0.001). Compared to CP, CI RRMS patients showed higher T2-LL (p = 0.02) and WM atrophy (p = 0.01). In the whole RRMS group, several cognitive tests correlated with brain tissue abnormalities (T2-LL, WM and GM atrophy); only verbal memory performances correlated with left hippocampal atrophy. Our results emphasize the role of T2-LL and WM atrophy in determining clinically evident cognitive impairment in MS patients and provide evidence that GM and hippocampal atrophy occur in MS patients regardless of cognitive status.

Computer-aided cognitive rehabilitation improves cognitive performances and induces brain functional connectivity changes in relapsing remitting multiple sclerosis patients: an exploratory study.

To better understand the effects of short-term computer-based cognitive rehabilitation (cCR) on cognitive performances and default mode network (DMN) intrinsic functional connectivity (FC) in cognitively impaired relapsing remitting (RR) multiple sclerosis (MS) patients. Eighteen cognitively impaired RRMS patients underwent neuropsychological evaluation by the Rao's brief repeatable battery and resting-state functional magnetic resonance imaging to evaluate FC of the DMN before and after a short-term (8 weeks, twice a week) cCR. A control group of 14 cognitively impaired RRMS patients was assigned to an aspecific cognitive training (aCT), and underwent the same study protocol. Correlations between DMN and cognitive performances were also tested. After cCR, there was a significant improvement of the following tests: SDMT (p < 0.01), PASAT 3" (p < 0.00), PASAT 2" (p < 0.03), SRT-D (p < 0.02), and 10/36 SPART-D (p < 0.04); as well as a significant increase of the FC of the DMN in the posterior cingulate cortex (PCC) and bilateral inferior parietal cortex (IPC). After cCR, a significant negative correlation between Stroop Color-Word Interference Test and FC in the PCC emerged. After aCT, the control group did not show any significant effect either on FC or neuropsychological tests. No significant differences were found in brain volumes and lesion load in both groups when comparing data acquired at baseline and after cCR or aCT. In cognitively impaired RRMS patients, cCR improves cognitive performances (i.e., processing speed and visual and verbal sustained memory), and increases FC in the PCC and IPC of the DMN. This exploratory study suggests that cCR may induce adaptive cortical reorganization favoring better cognitive performances, thus strengthening the value of cognitive exercise in the general perspective of building either cognitive or brain reserve.

Prevalence of patient-reported dysphagia in multiple sclerosis patients: an Italian multicenter study (using the DYMUS questionnaire).

OBJECTIVE: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) with a chronic course. Dysphagia represents one of the current challenges in clinical practice for the management of MS patients. Dysphagia starts to appear in mildly impaired MS subjects (EDSS 2-3) and becomes increasingly common in the most severely disabled subjects (EDSS 8-9). The aim of the present study was to evaluate the frequency and characteristics of patient-reported dysphagia in MS patients with a multicenter study using the recently developed DYMUS (DYsphagia in MUltiple Sclerosis) questionnaire. DESIGN: Data were collected in a multi-centre, cross-sectional study using a face-to-face structured questionnaire for clinical characteristics and the DYMUS questionnaire. RESULTS: 1875 patients were interviewed. The current study has shown a correlation between patient-reported dysphagia and EDSS and disease course but not with age, gender and disease duration. Questionnaires were divided into "patient-reported dysphagia-yes" (587, 31.3%) and "patient-reported dysphagia-no" (1288, 68.7%). Compared with the patient-reported dysphagia-no group, patients in patient-reported dysphagia-yes group had higher EDSS score (mean EDSS 4.6 vs. 2.8; p<0.001) and had a longer disease duration (mean duration 13 years vs. 11 years; p<0.001), while there was no significant difference in gender (32.7% vs. 30.5% male and 67.3% vs. 69.5% female) and in age composition (46.18 vs. 42.05). CONCLUSIONS: This study represents the largest, multi-centre sample of MS patients evaluated for patient-reported dysphagia utilizing an ad-hoc questionnaire for this condition.

Adenovirus infections in Bordeaux University Hospital 2008-2010: clinical and virological features.

BACKGROUND: Transversal epidemiological data on adenovirus infections in a hospital setting, including both immuno-competent and transplanted patients, are limited and rarely contain the application of molecular virology. OBJECTIVES: To describe the clinical characteristics and molecular epidemiology of adenovirus infections in Bordeaux University Hospital from 2008 to 2010 (clinical data, viral load and adenovirus species distribution). STUDY DESIGN: Adenovirus DNA quantification (qPCR) and typing (sequencing of hexon and protein VI genes and protein VI polymerase chain reaction (PCR) product analysis) were applied retrospectively to 215 clinical samples from 105 adenovirus-infected patients (2008-2010, Bordeaux University Hospital). Clinical data were recovered and analysed for 73 children and 25 adults. RESULTS: Viral loads were measured in stools, upper and lower respiratory fluids, blood, urine and digestive tract biopsies; the highest values were observed in stools and respiratory samples. Stool viral loads were comparable whatever the immune status. Adenovirus was typed in 57 patients: species Human adenovirus (HAdV) C dominated (n=36), followed by B (n=15), F (n=5) and D (n=1). We could demonstrate no association between HAdV species and load or clinical severity (observed in most patients). In the immuno-compromised, in contrast to immuno-competent patients, adenovirus infections presented no seasonal variation. Co-infections were frequent: mostly bacterial in immuno-competent children (33%) and viral in immuno-compromised people (34%). CONCLUSIONS: The species HAdV C dominates the local ecology, in both respiratory and digestive tract infections, independently of the patient's immune status. Adenovirus infections, often associated with co-infection of bacterial or viral agents, frequently lead to severe clinical consequences in hospital patients.

AAV-mediated photoreceptor transduction of the pig cone-enriched retina.

Recent success in clinical trials supports the use of adeno-associated viral (AAV) vectors for gene therapy of retinal diseases caused by defects in the retinal pigment epithelium (RPE). In contrast, evidence of the efficacy of AAV-mediated gene transfer to retinal photoreceptors, the major site of inherited retinal diseases, is less robust. In addition, although AAV-mediated RPE transduction appears efficient, independently of the serotype used and species treated, AAV-mediated photoreceptor gene transfer has not been systematically investigated thus so far in large animal models, which also may allow identifying relevant species-specific differences in AAV-mediated retinal transduction. In the present study, we used the porcine retina, which has a high cone/rod ratio. This feature allows to properly evaluate both cone and rod photoreceptors transduction and compare the transduction characteristics of AAV2/5 and 2/8, the two most efficient AAV vector serotypes for photoreceptor targeting. Here we show that AAV2/5 and 2/8 transduces both RPE and photoreceptors. AAV2/8 infects and transduces photoreceptor more efficiently than AAV2/5, similarly to what we have observed in the murine retina. The use of the photoreceptor-specific rhodopsin promoter restricts transgene expression to porcine rods and cones, and results in photoreceptor transduction levels similar to those obtained with the ubiquitous promoters tested. Finally, immunological, toxicological and biodistribution studies support the safety of AAV subretinal administration to the large porcine retina. The data presented here on AAV-mediated transduction of the cone-enriched porcine retina may affect the development of gene-based therapies for rare and common severe photoreceptor diseases.

Verteporfin photodynamic therapy for subfoveal choroidal neovascularization in pathologic myopia: a 12-month retrospective review.

PURPOSE: To evaluate the visual outcome of patients with subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia treated with verteporfin photodynamic therapy (PDT-V) and to verify the predictive role of visual and angiographic parameters. METHODS: This is a retrospective, interventional, consecutive case series study of subjects with subfoveal CNV secondary to pathologic myopia. All patients received PDT-V according to VIP guidelines. A complete ophthalmologic evaluation was performed on all patients and included best-corrected visual acuity (BCVA), fundus examination, and fluorescein angiography (FA, IMAGEnet System, Topcon Corp., Japan). CNV size (mm2) was directly measured on the early phase of the angiogram using the software included with the IMAGEnet package. All checks were scheduled at 3-month intervals for a period of 1 year. A review of medical and angiographic records was performed and assessed throughout a 12-month follow-up period. RESULTS: A total of 62 patients (62 eyes) were examined. Best-corrected visual acuity (BCVA) moderately decreased without reaching a statistically noticeable level throughout the followup; reduction in lesion size reached a significant level at the second checkup. A significant correlation between higher baseline BCVA and better final visual outcome was detected. CONCLUSIONS: Standardized PDT-V minimizes central vision deterioration in patients with CNV secondary to pathologic myopia. Better BCVA at presentation represents a good predictive sign.

A normal electro-oculography in a family affected by best disease with a novel spontaneous mutation of the BEST1 gene.

AIMS: To describe clinical and genetic findings in an Italian family affected by Best disease. METHODS: Five related patients underwent a complete ophthalmological assessment; genetic testing was performed by single-strand conformation polymorphism analysis and direct sequencing of the BEST1 gene. RESULTS: In three of five family members, the sequence analysis of the BEST1 gene revealed a single Phe-to-Leu transition at nucleotide 305 associated with clinical evidence of Best disease. Surprisingly, the electro-oculogram was normal in all affected patients. CONCLUSION: This study reveals a de novo mutation in the BEST1 gene never described before, sustaining the autosomal-dominant pattern of inheritance of the disease. Clinical evaluation showed phenotypic variability between affected members. In addition, these data suggest that a normal electro-oculography (EOG) does not rule out a diagnosis of Best disease, supporting instead the crucial role of molecular analysis.

Prevalence and behaviour of Bacillus cereus in a REPFED of Italian origin.

This paper reports on the prevalence and behaviour of Bacillus cereus in gnocchi, a REPFED of Italian origin. A survey of gnocchi under varying storage conditions, revealed that, although B. cereus was found in 33% of the samples, the contamination level was lower than 10(2) CFU/g for the unstored and the refrigerated (8 degrees C) samples. Counts increased with increasing storage temperatures and prolonged storage times in samples prepared without sorbic acid. The effect of different formulations (sorbic, citric and lactic acid) and storage conditions (8, 12 and 20 degrees C) have been evaluated in a challenge testing with spores of B. cereus. Results indicate that the use of sorbic acid in association with citric or lactic acid to pH 5.0 is effective in inhibiting growth of B. cereus and the anticipated shelf life of the product is safe even if temperature abuse occurs. If sorbic acid is omitted, lactic acid can inhibit B. cereus growth during storage at 8 degrees C. On the contrary, when temperature abuse occurs (12 and 20 degrees C), lactic or citric acid are not able to prevent growth of B. cereus.

A rare gastric ulcer complication: the gastrocolic fistula. A case report.

We report a case of gastrocolic fistula following a benign gastric ulcer, which is now a truly exceptional finding, due to the widespread use of H2-receptor antagonists and proton- pump inhibitors. A review of the literature shows that this condition warrants a complete diagnostic work-up to exclude more ominous underlying diseases. Careful attention to the symptoms of peptic ulcer and particular care with patients undergoing long-term treatments with drugs potentially harmful for the stomach are recommended.

Anosognosia for hemiplegia, neglect dyslexia, and drawing neglect: clinical findings and theoretical considerations.

In this paper different models of anosognosia are confronted and data concerning denial behaviors are presented that were collected on a selected population of right brain-damaged patients affected by motor and neglect disorders. Anosognosia for motor impairment and anosognosia for cognitive impairments were found to be dissociated, as well as anosognosia for the upper and lower limb motor impairments. These findings are then discussed in an attempt to choose the more suitable theoretical framework for interpreting the various disorders related to denial of illness.

Ocular involvement correlated with age in patients affected by major and intermedia beta-thalassemia treated or not with desferrioxamine.

We examined 25 patients affected from Cooley's disease and five by beta-thalassemia intermedia. The mean age was 15 +/- 6.3 years. Fifteen patients, (18 years or older) three of them affected by beta-thalassemia intermedia, presented ocular abnormalities. So it was impossible to establish a correlation between laboratory data and ocular damages; their observation, with reference to untreated beta-thalassemia subjects, suggested that ocular abnormalities cannot be only attributed to desferrioxamine treatment.

Cataract risk factors: blood level of antioxidative vitamins, reduced glutathione and malondialdehyde in cataractous patients.

Since many years experimental evidences have suggested an association between nutrition and lens opacities. A dietary deficiency of antioxidants and reactive oxygen scavengers may be involved in the pathogenesis of the "idiopathic" human senile cataract, as it has been demonstrated in some experimental cataracts. We tested the levels of ascorbic acid (vit. C), alpha-tocopherol (vit. E), reduced glutathione (GSH) and malondialdehyde (MDA) in the plasma or in the red blood cells (RBC) of 42 patients who were affected by surgically significant cataract and of 40 age-matched controls. Plasma vit. C mean level was 4.46 gamma/ml in cataracts and 4.62 gamma/ml in controls, while vit. E level was 7.70 and 7.09 gamma/ml respectively. RBC GSH was found to be 342 gamma/ml in cataracts and 346 in controls, while the MDA content was 4.06 picoMol/ml and 4.08 picoMol/ml respectively. The level of each tested nutrient or metabolite was not found to be statistically different between cataractous patients and controls, nor any significant trend was found to be present when the nutrients and metabolites were correlated to each other. Our results do not support the hypothesis of a nutritional deficiency in human senile cataracts. However, a defect in the antioxidative metabolism pathways could be present either systemically or at lens level.

[Experimental study of bonding resistance to vertical traction of a new photopolymerizing composite]. / Studio sperimentale sulla resistenza di legame alla trazione verticale di un nuovo composito fotopolimerizzante.

The Authors studied a new photopolymerizing orthodontic bonding resin, Trans-Band of 3M. Many ad vantages of the resin were described and particularly the short photopolymerizing time, 20 seconds only, and the uniformity of bond strengths obtained by 20 tests, all higher than 10 Kg. So, the Authors propose to experiment clinically Trans-Bond and, if it had the same ad vantages, to make use of it in place of Concise, the most used composite in orthodontics.