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Several evidences support the hypothesis that glutamatergic dysfunction may be implicated in the pathogenesis of schizophrenia and in the last few years great interest has been focused on the role of the N-methyl-D-aspartate receptor (NMDAR). Glutamate is the main excitatory neurotransmitter in human CNS and it plays a prominent role in synaptic plasticity, learning, and memory and other cognitive functions. Increasing interest in memantine add-on therapy in schizophrenic patients with negative and cognitive symptoms may suggest that memantine could be a new promising treatment in schizophrenia. The aim of this update was to evaluate clinical data about the memantine effectiveness in schizophrenic patients. Our systematic review of the literature highlights that memantine therapy in schizophrenic patients seems to improve mainly negative symptoms while positive symptoms and cognitive symptoms did not improve significantly., Competing Interests: The authors declare that they have no competing interests.

Introduction: Rasagiline is a selective, irreversible monoamine oxidase B inhibitor that ameliorates the symptoms of Parkinson's disease (PD) by inhibiting striatal dopamine metabolism. There is also evidence that monoamine oxidase B inhibitors increase melatonin levels in the pineal gland and may have a beneficial effect on sleep disorders, which are a common feature in patients with PD., Methods: This single-center, prospective, observational, 12-week study compared the effect of combination therapy with levodopa 200-300 mg/d + rasagiline 1 mg/d (n=19) with levodopa 200-300 mg/d alone (n=19) in the treatment of sleep disorders in patients with idiopathic PD., Results: After 12 weeks' treatment, mean sleep latency was significantly ( P <0.001) lower and the improvement in sleep latency from baseline was significantly ( P =0.001) greater in patients receiving levodopa + rasagiline than in patients receiving levodopa alone. Similarly, at the end of the study, the mean total sleep time was significantly ( P =0.002) longer and the improvement from baseline in mean total sleep time was significantly ( P =0.026) greater in patients receiving levodopa + rasagiline than levodopa alone. There were no significant differences between treatment groups for the mean number of awakenings reported at week 12 nor the change from baseline to week 12 in mean number of awakenings., Conclusion: Adding rasagiline to levodopa improved sleep outcomes and may be an appropriate option for patients with PD experiencing sleep disorders.

Objective: To apply next-generation sequencing (NGS) for the investigation of the genetic basis of undiagnosed muscular dystrophies and myopathies in a very large cohort of patients., Methods: We applied an NGS-based platform named MotorPlex to our diagnostic workflow to test muscle disease genes with a high sensitivity and specificity for small DNA variants. We analyzed 504 undiagnosed patients mostly referred as being affected by limb-girdle muscular dystrophy or congenital myopathy., Results: MotorPlex provided a complete molecular diagnosis in 218 cases (43.3%). A further 160 patients (31.7%) showed as yet unproven candidate variants. Pathogenic variants were found in 47 of 93 genes, and in more than 30% of cases, the phenotype was nonconventional, broadening the spectrum of disease presentation in at least 10 genes., Conclusions: Our large DNA study of patients with undiagnosed myopathy is an example of the ongoing revolution in molecular diagnostics, highlighting the advantages in using NGS as a first-tier approach for heterogeneous genetic conditions., (© 2016 American Academy of Neurology.)

We report the clinical, neuro-imaging, pathological and biochemical features of an Italian family in which two siblings have the Adult Polyglucosan Body Disease (APBD). APBD is a rare autosomal recessive disorder characterized by a gradually progressive involvement of both the central and peripheral nervous systems caused by the deficiency of the glycogen branching enzyme (GBE1). The two affected siblings, a 64-year-old man and his 67-year-old sister who had complained of urinary urgency and sporadic incontinence and also progressive gait difficulty for 6 and 7 years respectively, had severely impaired deep sensations on direct examination and a moderately severe symmetrical, axonal sensory-motor neuropathy on electrophysiological testing. GBE1 activity was below 25% of the normal rate in leukocytes and sural nerves. The siblings were homozygous for the novel GBE1 mutation p.N541D. All other members of the pedigree are heterozygous and manifest no symptoms, even in the very elderly. The affected siblings showed polyglucosan bodies (PBs) included within non-myelinating Schwann cells and within lymphocyte vesicles, which were positive for the autophagy markers P62 and LC3-II at immunofluorescence microscopy., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Aims: To assess in a sample of people with mental disorders: 1) fear of crime and perceived insecurity; 2) the association between fear of crime and insecurity; 3) the incidence of crimes., Methods: Twenty-four Italian mental health centres have been invited to participate in the study from the network of the Early Career Psychiatrists' Committee of the Italian Psychiatric Association. In each participating centre, the first 20 patients consecutively accessing the mental health centre between February and April 2011 have been recruited. All patients have been assessed using validated assessment tools., Results: The final sample consists of 426 patients. They are mostly female (70.1%), with a mean age of 45 years (± 13.5), and with a good level of education. Fifty-two percent of patients have a diagnosis of mood disorders, and 37.8% on anxiety spectrum disorders. About half of the sample declares that the most prominent feeling toward life is uncertainty. Almost all patients report to have at least one big fear, with the most frequently report being: 1) loss or death of a loved one (41.2%); 2) financial constraint (28.4%); 3) physical or mental health problems (26.5%)., Discussion and Conclusions: Our results show the presence of a common sense of uncertainty among patients, probably as a result of the historical moment we are facing. It is reasonable that this attitude toward life can have a detrimental impact on patients' psychological and physical wellbeing, contributing to high levels of distress. Further studies are needed in order to clarify the possible relationship between fears, uncertainty and mental disorders.

To elucidate the relationships between alexithymia, suicide ideation and serum lipid levels in drug-naïve adult outpatients with a DSM-IV diagnosis of Panic Disorder (PD), 72 patients were evaluated. Measures were the Panic Attack and Anticipatory Anxiety Scale, the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation (SSI) and the Montgomery Åsberg Depression Rating Scale (MADRS). Alexithymic patients showed higher scores on all rating scales and altered serum lipid levels than non-alexithymics. In the hierarchical regression model, the presence of lower HDL-C and higher VLDL-C levels and Difficulty in Identifying Feelings dimension of TAS-20 were associated with higher suicide ideation. In conclusion, alexithymic individuals with PD may show a cholesterol dysregulation that may be linked to suicide ideation. The authors discuss study limitations and future research needs., (Copyright © 2013 Elsevier Inc. All rights reserved.)

We investigated the efficacy of S-Adenosyl-L-Methionine (SAMe) augmentation in patients with treatment-resistant depressive disorder (TRD). Thirty-three outpatients with major depressive episode who failed to respond to at least 8 weeks of treatment with two adequate and stable doses of antidepressants were treated openly with fixed dose of SAMe (800 mg) for 8 weeks, added to existing medication. The primary outcome measure was the change from baseline in total score on Hamilton Rating Scale for Depression (HAM-D). The Clinical Global Impression of Improvement (CGI-I) was rated at the endpoint. Patients with a reduction of 50% or more on HAM-D total score and a CGI-I score of 1 or 2 at endpoint were considered responders; remission was defined as a HAM-D score ≤7. Secondary outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS) and the Sheehan Disability Scale (SDS). At 8 weeks, a significant decrease in HAM-D score was observed with response achieved by 60% of the patients and remission by 36%. Also a statistically significant reduction in SHAPS and SDS was observed. Our findings indicate that SAMe augmentation may be effective and well tolerated in stage II TRD. However, limitations of the present study must be considered and further placebo-controlled trials are needed.

Objective: The goal of this cross-sectional study was to evaluate the relationships between alexithymia and suicide ideation in 80 adult outpatients with a DSM-IV diagnosis of binge eating disorder (BED)., Methods: Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20); suicide ideation was assessed with the Scale of Suicide Ideation (SSI); severity of BED was assessed with the Binge Eating Scale (BES); and depressive and anxiety symptoms were evaluated, respectively, with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (Ham-A)., Results: Prevalence of current suicide ideation was 27.5% (n = 22) in this sample and 10 subjects (12.5%) had attempted suicide at some time in their lives. Subjects with alexithymia had more significant suicide ideation, a higher prevalence of current suicide ideation, and more previous suicide attempts than those without alexithymia. In a linear regression model, higher MADRS scores and higher scores on the Difficulty in Identifying Feelings/Difficulty in Describing Feelings dimensions of the TAS-20 were associated with increased suicide ideation., Discussion: Suicidal behavior is no less common in BED than in other eating disorders. Individuals with BED may show increased suicide ideation, especially in the presence of alexithymia and depressive symptoms, even if these symptoms are subclinical. The authors also discuss limitations of this study and future research needs.

Objective: The 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., Methods: A mixed male-female sample of 60 subjects (30 males and 30 females) was evaluated 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 > or =61). Alexithymics showed more severe negative and depressive symptoms and increased suicide risk than non alexithymics. 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.

Monogenic forms of Parkinson's disease (PD) provide an opportunity to examine mechanisms underlying phenotypic variation. Glutathione S-transferase (GST) has detoxification and antioxidative functions. To screen genetic variations in GST for an effect on the onset age (OA) of PD, we typed seven common genetic polymorphisms in five GST isoenzymes, M1, M3, P1, T1, and Z1, in 36 affected individuals of Italian or Greek origin with the alpha-synuclein A53T (PARK1) mutation. Mean OA was 45.2 years with a wide SD of 11.03 years, similar to that of idiopathic PD. Our allelic analysis showed that the subjects homozygous for the GSTP1 G-for-A nucleotide substitution at position 313 had a mean OA acceleration of 15.2 years (31.3 +/- 7.09 years, n = 3 vs. 46.5 +/- 10.50 years, n = 33, P = 0.020). The GSTP1 C341T substitution was associated with a 9.7-year acceleration of OA, but the significance was borderline (36.4 +/- 8.35 years vs. 46.7 +/- 10.85 years, P = 0.0519). After correction for the five genes examined, both results lose statistical significance. Nevertheless, our results suggest that further investigation in GSTP1 variants and PD pathogenesis is warranted in sporadic PD and that a search for toxins that accelerate PD OA should pay particular attention to GST-P1 substrates., ((c) 2006 Wiley-Liss, Inc.)

A retrospective study was performed on 27 patients with hepatitis C (HCV)-related mixed cryoglobulinemia (purpura, arthralgia, hepatitis, glomerulonephritis, peripheral neuropathy) to assess peripheral nerve involvement during follow-up of up to 8 years. All patients had the same degree of organ/system involvement initially and were clinically evaluated at least annually. All 27 patients received steroids; 15 also received recombinant interferon-alpha 2b (rIFN-alpha 2b). At first examination, neurological signs and electrodiagnostic findings consistent with peripheral neuropathy were found in 20 (74%) and in 24 (88.8%) patients, respectively. Neurological evaluation and electrodiagnostic data at 3 and 8 years revealed worsening of neuropathy, whereas the other manifestations of mixed cryoglobulinemia (MC) were stable. At the last examination, clinical and electrodiagnostic signs of neuropathy were found in 25 patients (92.5%), occurring in 1 of 3 patients with normal initial findings, and worsened in 8. A more severe neuropathy was observed in 3 (25%) of the patients treated with prednisone alone and in 6 (40%) of the patients additionally treated with rIFN-alpha 2b. Our data confirm that in patients with HCV-related MC, peripheral nerve involvement is frequent, is progressive, and does not seem to benefit by addition of rIFN-alpha 2b to steroid treatment.

Cerebrospinal fluid (CSF) levels of rT(3) were evaluated in 21 euthyroid patients with overt Alzheimer's disease (AD) and 18 matched healthy controls. The assessment also included transthyretin and total T(3) and T(4) CSF concentrations. Despite normal circulating thyroid hormone levels, AD subjects showed significantly increased rT(3) levels and an increased rT(3) to T(4) ratio in the face of unchanged CSF total T(4) and transthyretin levels. These results suggest an abnormal intracerebral thyroid hormone metabolism and possibly the occurrence of brain hypothyroidism, either as a secondary consequence of the ongoing process or as a cofactor in the progression of the disease.

Chorea-Acanthocytosis (CHAC) is an autosomal recessive disease characterized by neurodegeneration and acanthocytosis. Enhanced creatine kinase concentration is a constant feature of the condition. The mechanism underlying CHAC is unknown. However, acanthocytosis and enhanced creatine kinase suggest a protein defect that deranges the membrane-cytoskeleton interface in erythrocytes and muscle, thereby resulting in neurodegeneration. Acanthocytes have been correlated with structural and functional changes in membrane protein band 3--a ubiquitous anion transporter. Residue Gln-30 of band 3 serves as a membrane substrate for tissue transglutaminase (tTGase), which belongs to a class of intra- and extra-cellular Ca2+-dependent cross-linking enzymes found in most vertebrate tissues. In an attempt to cast light on the pathophysiology of CHAC, we used reverse-phase HPLC and immunohistochemistry to evaluate the role of tTGase in this disorder. We found increased amounts of tTGase-derived N(epsilon)-(-gamma-glutamyl)lysine isopeptide cross-links in erythrocytes and muscle from CHAC patients. Furthermore, immunohistochemistry demonstrated abnormal accumulation of tTGase products as well as proteinaceous bodies in CHAC muscles. These findings could explain the mechanisms underlying the increased blood levels of creatine kinase and acanthocytosis, which are the most consistent features of this neurodegenerative disease.

We describe the clinical, neuropathological and molecular findings from a patient affected with neuronal ceroid lipofuscinosis with a juvenile onset (JNCL). She was a 9-year-old right-handed girl with a normal birth and early developmental milestones. At the age of 4 the early symptoms began. Skin biopsy showed granular osmiophilic deposits (GRODs). Because JNCL with GRODs is caused by mutations in the CNL1 gene, we performed a molecular investigation by direct sequencing of nine exons of the CNL1 gene. This analysis revealed a novel mutation in homozygous form in the exon 7 that caused an aminoacid substitution at codon 222 (Leu --> Pro). Direct sequencing of the exon 7 in both parents showed the same substitution in heterozygous form.