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In recent years, the potential of smart technology to provide innovative solutions for disease management has raised high expectations for patients' and healthcare professionals' community. We developed a mobile app, called AIGkit, specifically designed for adult patients with Pompe disease, with the aim to help them manage the burden of illness-related factors, and also to provide clinicians with continuous tracking of each patient in real-time and ambient conditions of everyday life. We present the AIGkit as an innovative approach exploiting cutting-edge technology to improve quality of care and research into neuromuscular disorders.

We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family members complaining of reduced distance vision especially at dusk underwent complete ophthalmological examination. Whole-exome sequencing was performed to identify the gene responsible for myopia in the pedigree. Moderate myopia was diagnosed in the family which was associated to the novel missense variant c.1147A > G p.(Lys383Glu) in the prolyl 4-hydroxylase,alpha-polypeptide 2 (P4HA2) gene, which catalyzes the formation of 4-hydroxyproline residues in the collagen strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression level as well as decreased collagen hydroxylation and deposition in mutated fibroblast primary cultures compared to healthy cell lines. This study suggests that P4HA2 mutations may lead to myopic axial elongation of eyeball as a consequence of quantitative and structural alterations of collagen. This is the first confirmatory study which associates a novel dominant missense variant in P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are advisable to fully clarify genotype-phenotype correlations. We recently described a complex multisystem syndrome in which mild-moderate myopia segregated as an independent trait. A plethora of genes has been related to sporadic and familial myopia. More recently, in Chinese patients severe myopia (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family members complaining of reduced distance vision especially at dusk underwent complete ophthalmological examination. Whole-exome sequencing was performed to identify the gene responsible for myopia in the pedigree. Moderate myopia was diagnosed in the family which was associated to the novel missense variant c.1147A > G p.(Lys383Glu) in the prolyl 4-hydroxylase,alpha-polypeptide 2 (P4HA2) gene, which catalyzes the formation of 4-hydroxyproline residues in the collagen strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression level as well as decreased collagen hydroxylation and deposition in mutated fibroblast primary cultures compared to healthy cell lines. This study suggests that P4HA2 mutations may lead to myopic axial elongation of eyeball as a consequence of quantitative and structural alterations of collagen. This is the first confirmatory study which associates a novel dominant missense variant in P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are advisable to fully clarify genotype-phenotype correlations.

Late onset Pompe disease (LOPD) is characterized by significant motor disabilities, which affect in particular ambulation. Only one study reports on spatial-temporal parameters of gait assessed in a clinical heterogeneous group of unrelated patients. In this study spatiotemporal and kinematic gait patterns are described in a genetically homogenous group of LOPD patients using 3d movement analysis. 7 LOPD siblings, harbouring the same GAA mutations compound, were assessed with clinical scales and with 3d movement analysis to measure spatial-temporal and kinematic parameters during gait cycle and “sit to stand test”. Relevant abnormalities were observed either in spatial-temporal and kinematic parameters. The former consisted in a trend towards a decreased velocity and cadence, a prolonged time in double limb support, shorter step and stride length, and a widening of base of support; the latter in an increased anterior pelvic-tilt and posterior trunk-tilt during the whole gait cycle, a decreased pelvic obliquity, active hip extension and ankle dorsiflexion. This study shows, in homogenous group of LOPD patients, either spatial-temporal and kinematic deviations that may improve understanding of the musculoskeletal alterations, the evolution of disease and the answer to the enzyme replacement therapy.

Background: Natalizumab is an effective therapy in relapsing–remitting multiple sclerosis (RRMS), as it reduces lymphocyte transmigration through the blood–brain barrier (BBB) and induces lymphocytosis. Objectives: To analyse natalizumab-induced lymphocytosis (NIL) as a biomarker of drug efficacy. Materials and methods: We enrolled 50 relapsing–remitting (RR) and progressive–relapsing (PR) natalizumab-treated patients who had received at least 16 infusions and had been tested for lymphocyte count 24 hours before each administration. Clinical, MRI and hematological data were collected. Patients were divided into responders and sub-optimal responders according to the experience of at least one clinical and/or instrumental relapse during the treatment. Results: In 15 (30%) patients, an instrumental/clinical (14) or only instrumental (one) relapse occurred. We found a statistically significant difference in the mean percentage of the lymphocytes between the two groups over the first ten administrations ( p=0.04). The comparison between the time-to-relapse in the groups with high and low levels of lymphocytes showed that the group with a low NIL had a greater risk of relapse ( p=0.03). Conclusions: We suggest that NIL could be a biomarker of therapeutic efficacy in patients with RRMS treated with natalizumab, and that the risk of relapse may be higher in patients with a lower-than-expected NIL.

Aims: This article aims to (1) explore the levels of perceived insecurity in a sample of patients with mood or anxiety disorders and (2) assess whether living in ‘big cities’ can influence the levels of patients’ perceived insecurity and social contacts compared to living in a non-urbanized context. Methods: A total of 24 Italian mental health centers (MHCs) have been invited to participate. Twenty patients consecutively accessing the MHC have been recruited. All patients have been assessed using validated assessment tools. Results: The sample consisted of 426 patients, mostly female, with a mean age of 45 years. Globally, 52.2% of patients had a diagnosis of mood disorders, and 37.8% had anxiety disorders. Half of the sample declared that the main feeling toward life is uncertainty; higher levels of pessimistic views toward life have been detected in patients living in urban areas. A positive association between negative attitudes toward life and higher levels of depressive and anxiety symptoms, poor social functioning and higher levels of perceived psychological distress has been found. Conclusion: Our findings confirm the presence of a common sense of perceived uncertainty among our sample. Such attitude toward life can have a detrimental impact on patients’ psychological and physical well-being, contributing to high levels of distress.

Objective To evaluate the long-term results of patients who underwent bladder autoaugmentation (BA) in whom BA was used to treat a neuropathic bladder secondary to myelomeningocele, and who presented with a high-pressure/poorly compliant bladder. Patients and methods Eleven patients (eight girls and three boys, mean age 12.8 years, mean follow-up 6.6 years) were selected who had undergone BA between June 1991 and June 1994. At surgery, the patients had a poorly compliant bladder with a mean leak point volume (LPV) of 94 mL and a mean leak point pressure (LPP) of 58 cmH2O. None of the patients had vesico-ureteric reflux (VUR) at BA; five with grade III or IV VUR had undergone endoscopic correction in a day-surgery procedure using a suburethral collagen injection 1–3 weeks before BA. The patients were evaluated using clinical, urodynamic, radiological and endoscopic assessments. The LPV, LPP and safe bladder capacity (SBC, the cystometric volume at an intravesical pressure of 40 cmH2O) were recorded. Results At 1 year after surgery the mean LPV was 297 mL; none of the patients had VUR. The most recent mean LPV was 198 mL and the SBC 167 mL. The mean LPP remained stable at 60 cmH2O. At the last follow-up four patients had recurrent uni- or bilateral grade III–V VUR. At endoscopy the ‘augmented’ bladder portion had a smooth surface, compared with the grossly trabeculated lower half. From this finding all patients on clean intermittent catheterization were treated with oral oxybutynin. Some patients reported slightly less abdominal pain at maximum bladder volume; four needed pads to treat intermittent incontinence. On voiding cysto-urethrography, one patient had an hourglass-shaped bladder. Five patients recently underwent ileocystoplasty because of recurrent urinary tract infection, high-grade VUR and incontinence. Conclusion These results do not justify the routine use of BA in hypertonic/poorly compliant bladders secondary to myelomeningocele. The mean follow-up of 6.6 years showed that this procedure failed in seven of 11 patients. Further studies might be able to identify subgroups in which this approach may be more appropriate.

IntroductionPeripersonal space has been defined as the area immediately surrounding the body in which interactions with a person or an object can occur. Larger peripersonal space may reflect discomfort in close interpersonal situation or cognitive deficit. Individuals with schizophrenia are more sensitive to social stimulation. The capacity to provide accurate judgments of peripersonal space boundaries depend on the capacity to create an organized and structured mental representation that integrates signals from different sensory modalities and brain regions.ObjectivesWe conducted a study on personal space in patients with schizophrenia using a paradigm that was not affected by emotional and social interference.AimsWe aimed to investigate the characteristics of personal space in patients with schizophrenia.MethodsWe recruited 20 schizophrenic patients according to DSM-V criterion and 20 healthy volunteers, matched by gender and age. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Participants performed the peripersonal space (PPS) task. Collected data underwent statistical analyses.ResultsSchizophrenic patients demonstrate a stronger/weaker need for personal space, than the comparison group, depending on the score of negative and positive symptom, as assessed by using the PANSS even without emotional and social interference.ConclusionsInterpersonal interactions between the individual with schizophrenia and people in their immediate environment can lead to increased symptomatology. Social isolation is one of the most primary causes of poor quality of life in mental illnesses. Better understanding of the mechanisms for abnormal interactive behavior could provide significant valid guidelines for innovating intervention programs.Disclosure of interestThe authors have not supplied their declaration of competing interest.

IntroductionPatients affected by bipolar disorder type I (BD-I) show a significant emotional impairment during both acute and euthymic phases of the illness, but the influence of negative life experiences is not yet fully understood.ObjectivesAim of the present study was to investigate the role of previous traumatic events on negative emotion processing in euthymic BD-I patients.MethodsEighteen euthymic BD-I patients, 7 reporting past traumatic events (T-BD-I), but free of post-traumatic stress disorder (PTSD) symptoms at the moment of the evaluation and 11 never exposed to traumas (NT-BD-I), were compared to 24 not traumatized controls (NC). All participants performed a IAPS-based emotional task: they were required to identify vegetable items (targets) among neutral or negative pictures. Accuracy (percentage of correct responses) and mean reaction times (RT) were recorded.ResultsT-BD-I performed similarly to NC and significantly better than NT-BD-I in terms of accuracy (Fig. 1). No significant between-group effects were observed for mean RT.ConclusionsA previous history of traumatic events, without current PTSD symptoms, may significantly impact the negative emotion processing in euthymic BD-I. Interestingly, traumatized patients showed a better accuracy when processing both neutral and negative images, thus suggesting that paying more attention to external stimuli may be a successful compensatory mechanism to cope with potential environmental threats.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Daily rhythms regulate everiday life and sleep/wake alternation is the best expression of this. Disruptions in biological rhythms is strongly associated with mood disorders, often being the major feature of this, major depressive disorder first of all. Although stabilization of rhythms produced by treatments have important outcome on therapeutic efficacy, insomnia often remains an unresolved symptom when major depression has otherwise been successfully treated with antidepressant. We review scientific literature in order to better clarify how to better approach insomnia as a clinical aspect to investigate and to early treat while treating other psychiatric conditions, major depression in particular. Insomnia is associated with impaired quality of life. It can be resolved with adequate diagnosis and treatment: it should be considered a comorbid condition and should be early identificated and treated in a multidisciplinary way, so that the ideal of treatment for patients with treatment resistant insomnia in major depression is an integration of non-pharmacologic measures, along with judicious use of medication, often used as an adjunctive therapy.

The abnormal neuronal excitability hypothesized in myotonic dystrophy (MD) might contribute to psychomotor and behavioral disturbances of MD patients. To gain new insights into the pathophysiology of MD, we determined whether the antiarrhythmic drug hydroquinidine would ameliorate slow saccadic eye movements (SEMs), apathy and hypersomnia in MD patients. SEMs were selected as simple modality for psychomotor investigation. The study was conducted in a randomized, placebo-controlled, double-blind, crossover manner. Ten ambulatory patients without contraindications to hydroquinidine administration were enrolled. Hydroquinidine (450 mg/day) or placebo was given orally for 6 weeks with a washout period of 6 weeks between treatments. SEMs were recorded by electrooculography and analyzed by a computer system. Two patients withdrew in the first week of active treatment because of nausea and epigastralgia. Hydroquinidine significantly increased the normalized peak saccadic velocity and shortened the saccadic reaction time compared to placebo. The drug's effects on apathy and hypersomnia are presented in a companion paper.

We report a 26-year-old Italian man with X-linked Charcot-Marie-Tooth (CMT) disease type 1 (CMT-X1) and a negative family history for neuromuscular diseases. Clinical and electrophysiological examinations of the patient's mother and siblings were normal. Molecular analysis by polymerase chain reaction – single-strand conformation polymorphism (PCR-SSCP) on genomic DNA from the patient and all members of his family revealed a C-to-T transition in codon 8 of exon 2 of the connexin-32 (Cx32) gene on the X chromosome only in the patient. This transition in the 5'-coding region, resulting in a Thr-Ile substitution, is likely to be the cause of CMT phenotype in our patient, and it represents a new de novo mutation of the Cx32 gene.

We report a case with refractory insomnia. We diagnosed her case as depression with high levels of anxiety, weakness, with diminished ability to think or concentrate and with a sensory-motor disorder. Although this last symptom was very distressing, it did not satisfy the criteria for RLS (Restless Legs Syndrome). After treatment with paroxetine (20 mg) and zolpidem (10 mg), anxiety and mood deflection were attenuated. Nevertheless, a mild depression, an intermittent awakening (fragmentation of the sleep-wake rhythm) and subsyndromal RLS persisted. Her resistant insomnia was treated with benzodiazepine sleeping drugs (triazolam 0.25 mg, lorazepam 2.5 mg, fluorazepam 30 mg) with only partial insomnia remission, antidepressants (trazodone 150 mg RP, mirtazapine 15-30 mg, agomelatine 50 mg) and antipsychotics (levomepromazine 25 mg, zuclopentixol 25 mg) without results. Her intractable insomnia was markedly responsive to pregabalin without side effects. Our hypothesis is that the therapy with pregabalin may be indicated for resistant insomnia associated with subsyndromal RLS, even when the latter does not satisfy fully all the criteria for diagnosis.

There is growing interest in the role of neurotrophins in the pathophysiology of schizophrenia. Neurotrophins are a large family of dimeric polypeptides that promote the growth and the differentiation of developing neurons in the central and peripheral nervous systems as well as the survival of neuronal cells in response to stress. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) concentrations are here reviewed in relation to medication-naive early psychotic patients and in medicated chronic schizophrenic patients. Most data point to decreased plasma and serum NGF and BDNF concentrations in naive drug and in medicated schizophrenic patients compared to healthy controls. Higher BDNF levels were observed in patients with the paranoid subtype of schizophrenia. Low serum BDNF levels were associated with reduction in hippocampal volume (HV) at the onset of schizophrenia. Evidence on the correlation between BDNF levels and positive and negative schizophrenic symptoms were ambiguous. There are contrasting results on a possible correlation between increase in BDNF concentrations and treatment with antipsychotics. Antipsychotic treatment can elevate NGF values, specifically atypical. Growth factors might be good candidates as prognostically and diagnostically useful markers in schizophrenia.

Psychiatric disorders are frequently associated with disturbances of sleep and circadian rhythms. This review focus on the relationship between sleep disturbances and eating disorders. In the first part are discussed the presence of sleep disorders among patients suffering from anorexia nervosa and bulimia nervosa, the macrostructure and microstructure of theirs sleep, the differences between the various subtypes in ED patients, the dreams of eating disordered patients and their recurrent contents. In the second part, there are treated sleep disturbances in binge eating disorder and other eating disorders not otherwise specified, such as nocturnal (night) eating syndrome and sleep-related eating disorder. In the third part, there are presented data concerning the neurobiological and neuroendocrinological correlates between feeding, metabolism, weight restoration and the processes regulating sleep. In conclusion, possible future investigations are proposed.

Despite a wide range of available antidepressants, the effect of the treatment is often suboptimal and there is a need for more effective and better tolerated drugs. Unlike other antidepressants, agomelatine represents a new approach to depression with an innovative mechanism of action. It is an agonist of melatoninergic receptors MT1 and MT2 and a selective antagonist of 5-HT2c receptors. In this open-label 8-week study we aimed to investigate the efficacy of agomelatine on depressive symptoms in patients with major depression. Secondary endpoints were the effect of agomelatine on anhedonia. Thirty major depressive patients received a flexible dose (25-50 mg; per os, daily) of agomelatine. Depressive (Hamilton Depression Scale) and anxious (Hamilton Anxiety Scale) symptoms, anhedonia (Snaith Hamilton Rating Scale), and sleep quality (Leeds Sleep Evaluation Questionnaire) were assessed. Twenty-four patients (80%) completed 8 weeks of treatment. Significant improvements were seen at all visits on the HAM-D (p.05), HAM-A(p.01), SHAPS (p.05), LSEQ (p.05). Nine subjects (30%) were responders and 5 (17%) remitters at week 1; 18 (60%) were remitters by the end of the trial. There was no serious adverse event. No aminotrasferase elevations were noted. In line with previous studies, in which agomelatine was associated with early clinical improvement, this study also provides evidence of an early response and the findings of improvements in depression scores. Moreover, this is the first study where agomelatine was effective in the treatment of anhedonia. Additional trials are needed to delineate the place of agomelatine in the contemporary pharmacotherapy for depressive disorders.

MyoD is a myogenic regulatory factor with a critical role in skeletal muscle development and regeneration. As muscle regeneration comes with an inflammatory process, it has been proposed that the inflammatory cells can play an important role in the induction of muscle fibres regeneration. The aim of the present work was to verify if a cyclooxygenase inhibitory drug (ketoprofen) would alter the normal expression of MyoD in a regenerating rat soleus muscle after an over-load lesion. Using immunohistochemical techniques, the numbers of m-cadherin-positive cells, a selective marker of satellite cells, and MyoD-positive cells were evaluated in functionally overloaded rat soleus muscles 4 days after a gastrocnemius tendon cut. The same study was conducted either with four rats injected with ketoprofen (100 mg/kg b.w./day) or with four rats injected with saline solution. The data obtained showed a very large decrease in the number of MyoD positive/m-cadherin positive cells in the ketoprofen injected group compared to the control group. Although further studies are needed to elucidate the sequence of biochemical events that induce a reduction of MyoD expression due to ketoprofen, the results demonstrate that prostaglandin synthesis is required for the induction of MyoD expression and that ketoprofen can affect this expression, with possible adverse effects on muscle regeneration.

A retrospective, cross-sectional study was performed on a series of HCV-related mixed cryoglobulinemia (HCV-MC) patients to assess autonomic neuropathy (AN) and its relation to peripheral neuropathy (PN). Thirty consecutive patients affected by HCV-MC underwent clinical, neurological and electrodiagnostic examinations. Autonomic nervous system (ANS) involvement was assessed by functional cardiovascular tests and sympathetic skin response (SSR) evaluation. Sural nerve biopsy was performed in 10 patients with PN. All patients received steroids, 15 also received recombinant interferon-alpha2b (RIfn-alpha2b). PN occurred in 27 patients (90.0%) and AN in 4 (13.3 %) all with signs of PN. SSR was the autonomic test more frequently altered. Biopsy disclosed axonal degeneration more evident in the 4 patients with AN. Three out of 4 patients with AN received steroids and rIFN-alpha2b and 1 steroids alone. In our study on HCV-MC, it was concluded that AN can occur also without dysautonomic symptoms, SSR appears to be one of the optional tests to use together with dysautonomic tests to identify AN and finally PN and AN do not seem to be positively influenced by addition of rIFN-alpha2b to steroid treatment.

We report a clinical case of a patient with a manic episode after taking methylphenidate (up to 120mgr per day) and cannabis in order to improve performance during exam period. He was hospitalized for disorganized behaviour, increased aggresion, delusions, grandiosity. He was affected by attention deficit and hyperactivity during childhood and recent episods of subthreshold depression. The therapy consisted of benzodiazepine and hydratation. In conclusion clinicians shuould ha ve caution in prescribing neurostimulant in vulnerable subjects.

Introduction Orthorexia nervosa (ON) is an alleged eating disorder in which the person is excessively preoccupied with healthy food. First described by Bratman in 1997, ON entails a fixation on healthy food or a health food dependence. The term orthorexia nervosa arises from the Greek words orthos (=accurate) and orexis (=hunger) meaning obsession with healthy food and proper nutrition. Fears and worries about health, eating, and the quality of food are significant. Objectives We investigated the prevalence of ON in a a population of young Italian adults by using a validated questionnaire (ORTO-15). Aims We aimed to assess the prevalence of ON in a large sample of general population and to identify some possible specific correlation such as gender and Body Mass Index (BMI). Methods 1453 adult subjects from the general population were administered the ORTO-15 test and investigated for gender, age and BMI. Statistical analyses were performed referring to diagnostic threshold (40). Results Orthorexia had a 10,9% prevalence in our sample, with a female prevalence statistically significant (female vs male= 72,8% vs 27,2%). Moreover, age and Body Mass Index did not seem to be significant factors. Conclusions ON is not currently considered as a full-fledged and discrete mental disorder. Again, the definition and diagnostic criteria of ON remain unclear. Further studies are needed to clarify appropriate diagnostic methods and the place of ON among psychopathological categories. This should be accompanied by a vigorous research effort aimed at understanding the core nature of this condition.

reduction of BMI (p< 0.05) was measured between t0 and t1, however body weight remained static over the 6-week period. The power of the test was, however, quite low (14.2%). Conclusions: Our results suggest that magnesium citrate supply is useful in promoting adherence to a hypocaloric diet, in terms of reduction in BMI, in overweight and obese middle-aged women. In particular, this effect seems to be mediated by a major capacity to impose a voluntary control on disordered alimentary habits in response to hedonic signals derived from highly palatable foods typical of today’s diet.

Klippel-Trenaunay syndrome (KTS) is a rare congenital malformation of unknown etiology characterized by cutaneous hemangiomas, venous varicosities and bony and soft tissues hypertrophy usually affecting one limb. Several complex anomalies involving various organs and systems have been described, whereas involvement of the peripheral nervous system has rarely been reported in KTS. We describe the case of a 67-year-old woman with KTS and peripheral neuropathy related to the presence of epineurial microscopic arteriovenous anastomoses (AVA) and endoneurial vascular coils in sural nerve biopsy from both hypertrophic and non-hypertrophic limb. The maintenance of AVA has been proposed to be the cause of the hypertrophy. The observation in our patient of AVA in non-hypertrophic limb contrasts with this hypothesis.

Measurements of magnetic fields in the prototype of the OPERA spectrometer are re-ported. Both the magnetic flux B in the iron and the fringe field in air have been measured by means of pick up coils and Hall probes. These measurements are aimed to the deter-mination of the value of B in the bulk of the spectrometer for different currents and test the magnetic properties of the material in a full-scale prototype. Moreover, comparisons with simulations based on finite-element analysis have been carried out.

Objective To evaluate the efficacy of MAGPI's procedure in children who had a meatal regression after hypospadias repair. Patients and methods Twenty-one children affected by post-hypospadias repair meatal regression underwent a modified MAGPI repair between January 1992 and January 1999: the patients, aged between 3 and 12 years (mean 5.9), had previously undergone hypospadias repair according to the techniques of Duplay (11 patients), Mathieu (2 patients), Snodgrass (5 patients) or the onlay buccal mucosa graft (3 patients). The outcome of the procedure was evaluated in terms of urinary stream and cosmetic appearance. Results The results were good in 18 patients, fair in 2, unchanged in 1. Conclusions MAGPI's repair has proven to be very effective as a secondary procedure in meatal regression after hypospadias correction, with minimal morbidity and a highly successful outcome in terms of satisfactory functionality and cosmetic appearance, and the recovery of gaps as large as 9 mm.

In HCV-related mixed cryoglobulinemia (MC) a peripheral neuropathy (PN) may occur. To evaluate the prevalence and the characteristics of PN, 133 consecutive patients with HCV-MC (117 type II, 16 type III) were studied. Neurologic evaluation was performed according to the guidelines of Italian Group for the Study of Cryoglobulinemias, using a neurological disability score and a neurological symptom score. In 52/133 patients an electrophysiologic study (ENG) of ulnar, peroneal and sural nerves was performed. For 27/52 patients ENG data registered at different times (interval 12-96 months) were available. In 11 patients a sural nerve biopsy was obtained. An overt PN, mostly as sensory asymmetrical or symmetrical nerve impairment, was found in 107/133 patients (80.4%). ENG abnormalities-reduction or absence of sensory and sometimes of motor action potential, normal or slightly impaired nerve conduction velocity, consistent with axonal damage- were detected in 48/52 patients (92.3%). In 26 out of the 27 patients observed at different times an evolution of PN was found. Nerve biopsies showed a prevalent axonal damage, swollen endothelial cells in epi- and perineurial vessels and scarce mononuclear perivascular infiltrates. No leukocytoclastic vasculitis was observed. Immunoglobulins and complement in sub-perineurial vessel wall were detected. CONCLUSIONS: In HCV-MC a PN is frequent. It is mostly a sensory and progressively worsening axonopathy. Different mechanisms may be involved in the pathogenesis of this disorder and a direct role of HCV cannot be excluded.

Fecal incontinence, with or without persistent constipation is often underestimated in children affected by spina bifida. Medullar lesions to the L-S metameres result in a slowing of rectal and/or rectal-sigmoid motility, loss of anal or rectal sensation, deranged external anal sphincter function, altered motility of the anal levator muscles, and loss of motor coordination of the internal sphincter. We conducted an electromyographic and electromanometric evaluation of the anorectal tract in a group of children affected by myelomeningocele (MMC) in an attempt to evaluate the degree of functional damage and to provide appropriate treatment.Anorectal manometry was conducted in 83 children affected by MMC (2-16 yrs, mean age: 8.4 yrs); surface electromyography was also performed in 37 of these children. We thus evaluated overall sphincter pressure, the inhibitory anal reflex, the rectal sphincteric reflex and rectal motility during stimulation and at rest. Recording perfusion catheters (0.1 ml/sec) were placed at rectal and anal level; rectal stimulation was conducted with an endorectal balloon.In all patients there was a reduction in overall sphincter pressure (15-25 mmHg; n.v. 45+/-25 mmHg) and the functional length of the anal canal (1-1.8 cm) compared with age matched controls. The inhibitory anal reflex was normal in all patients, although its amplitude, duration and sensitivity were not constant. Similar findings were obtained for the rectal-sphincteric reflex. The rectal sigmoid motility results were difficult to interpret: sudden, fast and high pressure waves of peristaltic progression were followed by prolonged pauses. No correlation was found between urodynamic and anorectal manometric data. Treatment consisted in daily emptying of the rectum so as to avoid fecal retention. Fifteen patients, who presented prolapse and sphincteric hypotonia (/=10 mmHg), underwent cerclage by 2/0 prolene, with sustained good RESULTS.While evaluation parameters of the neuropathic bladder are well standardised, data on the neuropathic rectum are contradictory. Moreover, the results of functional examination are not always an aid to treatment strategy. Therefore, further studies are required to establish an appropriate diagnostic-therapeutic protocol.

To determine objectively, using uroflowmetry, the functional results of the tubularized-incised plate urethroplasty to repair midshaft-proximal hypospadias.Twenty-one patients (mean age 4 years, mean follow-up 1.8 years) were selected from those undergoing surgery between January 1996 and January 1998 at our institution. All patients had midshaft-proximal hypospadias and were treated using the Snodgrass technique. Patients were included if they were able to void volitionally and had no fistula. The flow pattern, maximum (Qmax) and mean flow rate (Qave) were measured; the results were expressed as percentiles and compared with published values from normal children. The Qmax and Qave were considered normal if25th percentile, as equivocally obstructed when in the 5-25th percentile and obstructed if5th percentile.Fourteen patients were considered normal, four as equivocally obstructed and three as obstructed. Of the second group, one patient had a urethral diverticulum at the native meatus (confirmed by voiding cysto-urethrography) and the remaining three patients had meatal stenosis that responded to dilatation, with normal flow in two and improvement in the other. Of the obstructed group, one patient responded to dilatation and two underwent meatoplasty.The tubularized-incised plate repair provides satisfactory functional results for midshaft-proximal hypospadias; uroflowmetry is an important noninvasive tool to evaluate this technique. A long-term follow-up is needed to confirm these results.

Interferon (IFN)-beta has become a widespread therapy for multiple sclerosis. As already reported for IFN-alpha, thyroid autoimmunity and dysfunctions have been observed also in course of IFN-beta therapy. Nevertheless, very few cases of Graves' disease, occurred in such condition, have been reported in literature. We here describe the case of a 40-year-old female affected by multiple sclerosis, who received IFN-beta-1b, 8 million IU s.c. every other day for her condition. After 22 months of cytokine administration, she developed a severe Graves' disease with persistently positive TR-Ab which suggested the withdrawal of the treatment. Our patient had performed a complete thyroid evaluation with normal findings, before and during the first 6 months of therapy. This case suggests that patients undergoing long-term IFN-beta therapy should be monitored for thyroid hormones and antibodies throughout the treatment as thyroidal side effect can be a late event.

An abnormal neuronal excitability in myotonic dystrophy (MD) might contribute to psychomotor and behavioral disturbances of MD patients. To gain new insights into the pathophysiology of MD, we determined whether the antiarrhythmic drug hydroquinidine could ameliorate apathy and hypersomnia besides slow saccadic eye movements in these patients. The study was conducted in a randomized, placebo-controlled, double-blind, crossover manner. Ten ambulatory patients without contraindications to hydroquinidine administration were enrolled. Hydroquinidine (450 mg/day) or placebo was given orally for 6 weeks with a washout period of 6 weeks between treatments. Apathy was evaluated by means of the apathy evaluation scale (AES) and hypersomnia by a sleep diary. Two patients withdrew in the first week of active treatment because of nausea and epigastralgia. The drug significantly reduced AES scores and daily sleep time compared to placebo. Thus, hydroquinidine can ameliorate apathy and hypersomnia in MD. However, the possibility of proarrhythmia and the high frequency of cardiac disturbances in MD seriously limit the therapeutic perspective. The effects on eye movements are presented in a companion paper.

Objective: To conduct the genotype-phenotype correlation in a family in which several individuals share clinical and electrophysiologic features of paramyotonia congenita (PC). Background: PC, hyperkalemic periodic paralysis (HyperPP), and potassium-aggravated myotonias form the group of hereditary sodium channelopathies. Each of these disorders is associated with different point mutations in SCN4A , the gene encoding the α-subunit of the adult human skeletal muscle sodium channel. However, in HyperPP families, evidence of a causative gene different from SCN4A has been found. Methods: We conducted direct clinical examination, electrophysiologic (EMG/electroneurographic) and cardiologic studies, as well as laboratory screening in several affected and nonaffected members of the family. We performed the genotype-phenotype correlation by microsatellite linkage and cDNA-mutation analyses of the SCN4A gene. Results: Affected members in this family showed clinical and electrophysiologic features typical of PC. The disease phenotype segregated with the chromosomal region that includes the SCN4A gene. Analysis of the entire cDNA sequence of the SCN4A gene in the index case disclosed a G3826A transition, which results in the Val1276Ile substitution. However, PCR–single-stranded confirmation polymorphism and direct sequencing analysis of the segment coding for Val-1276 on genomic DNA confirmed the G3826A transition in the index case but was negative in 11 affected members of the family; however, neither mutations nor aberrant splicings causative of the PC phenotype in this family were found on SCN4A . Conclusion: The existence of a second gene different from SCN4A that can give rise to a clinical PC phenotype can be speculated upon.

Many authors have shown the role of uroflowmetry in the follow-up of patients operated on for hypospadias. This technique has also been used to assess the validity of the operative technique.Sixty patients have been selected among those operated on for hypospadias from January 1990 till January 1996 at the Pediatric Surgery Department of the Second University of Naples, Italy. These patients underwent uroflowmetry with a rotating disk sensor at clinic. Postoperative time at uroflowmetry ranged between 6 months and 6 years. Flow pattern, maximum flow rate (Q max) and mean flow rate (Q ave) were measured. Results are expressed as percentiles and compared with those obtained from Toguri. Q max and Q ave greater than 25 degrees percentile were considered normal; Q max and Q ave between 25 degrees and 5 degrees percentile were considered query obstructed; Q max and Q ave below the 5 degrees percentile were considered obstructed.Forty-two patients (70%) presented values above the 25 degrees centile, 8 patients (13.4%) presented an obstructed-like flow and 10 children (16.6%) showed a query obstructed flow. Three patients from the latter group presented within three months an obstructed-like flow.Uroflowmetry is an important tool in the follow-up of patients operated on for hypospadias that are at risk for stenosis and then requiring a further treatment, either dilatation or surgery.

Basilar artery dolichoectasia, ectasia of internal carotids and intracranial aneurysm have been described in late-onset glycogenosis II (GSD II). Incidence of these anomalies and their relationship to the genotype are unknown. Also, because studying cerebral vessels is not recommended for diagnosis of late-onset GSDII, the frequency of these anomalies may be underestimated. Therefore, we investigated the occurrence of vascular anomalies in eight siblings (4M, 4F) of an Italian family affected by late-onset GSDII due to a compound mutation (c.118C>T in exon 2 and c.2647-7G>A in intron 18) of the acid α-glucosidase (GAA) gene (17q21-23).

Introduction The primary aim of the present study was to compare the effects of agomelatine and venlafaxine XR on anhedonia in patients with Major Depressive Disorder. Secondary endpoints were to test its antidepressant and anxiolytic efficacy. Methods Sixty patients received randomly agomelatine (25–50 mg/day; N = 30) or venlafaxine XR (75-150 mg/day, N = 30). Psychopathological assessment was performed at baseline and over eight weeks of treatment with the Snaith Hamilton Rating Scale (SHAPS), the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A) and the Clinical Global Impression (CGI). Results Both groups showed an overall significant reduction in times for SHAPS, HAM-D and HAM-A. A significant difference between times was observed for SHAPS scores in Agomelatine group: from baseline of 6.5 (T0) to 4 at week 1 (−2.5) (T1), 3.5 at week 2 (−3.0) (T2), and 3.4 at week 8 (−2.9) (T3). In the venlafaxine group, the reduction on SHAPS scores was not significant between visits (p = .08). At the last observation a significant difference between groups in favour of agomelatine was observed for SHAPS scores (D = 2.2; p Discussion Agomelatine showed significantly greater efficacy on anhedonia and at least similar antidepressant efficacy to venlafaxine in patients with Major Depressive Disorder, with a better clinical improvement. Therefore, the efficacy of agomelatine on anhedonia, a potential trait marker of vulnerability for depression, holds particular importance in the treatment of patients with depressive features.

Introduction Working memory deficits have yet been reported in Schizophrenia and Bipolar Disorder and suggested to be trait markers of those disorders. A few data are reported for Recurrent Unipolar Depression. Objectives and aims Aim of the present study was to evaluate working memory resources in a group of euthymic unipolar subjects. Methods Fifteen outpatients (13 females) affected by Recurrent Unipolar Major Depression, were recruited by the Department of Mental Health of Ortona (Chieti), Italy, and compared to 15 age and gender matched healthy comparisons in terms of Working Memory resources. Inclusion criteria were: a DSM IV diagnosis of Recurrent Major Depression and a condition of euthymia, defined as a Hamilton Depression Scale (HAM-D) score Results Patients showed a significant lower performance, with respect to normal comparisons, limited to the highest level of difficulty working memory task (graph.1). Conclusions In our group of unipolar subjects, working memory resources seemed to be reduced during euthymic periods, thus significantly affecting quality of life and social functioning. Download : Download full-size image

ObjectivesThe aim of the present study was to evaluate the prevalence of alexithymia and its relationships with psychopathological features and suicide risk in a sample of adult patients with a DSM-IV diagnosis of paranoid schizophrenia.MethodA mixed male-female sample of 60 subjects (30 males and 30 females) was evaluetd with the following rating scales: Toronto Alexithymia Scale (TAS-20), Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), Calgary Depression Scale for Schizophrenia (CDSS), Scale for Suicidal Ideation (SSI), State-Trait Anxiety Inventory (STAI). RESULTS. 22 subjects (36.7%) were categorized as alexithymic (TAS-20 scores ≥ 61). Alexithymics showed more severe negative and depressive symptoms and increased suicide risk than nonalexithymics.However, the results of a linear regression with SSI score as dependent variable showed that Difficulty in Identifying and Describing Feelings dimensions of TAS-20 and higher CDSS scores were significantly associated with higher scores on the Scale for Suicide Ideation. Conclusions: The presence of alexithymia in schizophrenia may be related to higher risk of suicide ideation and more severe depressive symptoms, independently by the severity of positive and negative symptoms. However, results are preliminary and limitations must be considered.

IntroductionToday there is a large number of antidepressant drugs. However, the effect of treatment is often suboptimal. Unlike other antidepressants agomelatine has a novel neurochemical mechanism. It is an MT1 and MT2 melatonergic receptor agonist and a selective antagonist of the 5-HT2C receptors. In this open-label 8-week study we aimed to investigate the efficacy of agomelatine on depressive symptoms in patients with major depression. Secondary endpoints were the effect of agomelatine on anhedonia.MethodsThirty major depressive patients received a flexible dose (25–50 mg; per os, daily) of agomelatine. Depressive (Hamilton Depression Scale) and anxious (Hamilton Anxiety Scale) symptoms, anhedonia (Snaith Hamilton Rating Scale), and sleep quality (Leeds Sleep Evaluation Questionnaire) were assessed.ResultsTwenty-four patients (80%) completed 8 weeks of treatment. Significant improvements were seen at all visits on the HAM-D (p< .05), HAM-A(p< .01), SHAPS (p< .05), LSEQ (p< .05). Nine subjects (30%) were responders and 5 (17%) remitters at week 1; 18 (60%) were remitters by the end of the trial. There was no serious adverse event. No aminotrasferase elevations were noted.DiscussionIn line with previous studies, in which agomelatine was associated with early clinical improvement this study also provides evidence of an early response and the findings of improvements in depression scores. Beside this is the first study where agomelatine was effective in the treatment of anhedonia. Additional trials are needed to delineate the place of agomelatine in the contemporary pharmacotherapy for depressive disorders.