Neurological Soft Signs Total Score Research Articles

Relapse in schizophrenia: The role of factors other than non-adherence to treatment.

Relapse rates are very high in schizophrenia. However, little is known about the predictors of the time to relapse other than treatment non-adherence. We investigated possible risk factors for the time to relapse in patients with first-episode schizophrenia (n = 107) who received assured treatment by way of long-acting injectable antipsychotic over 24 months and who underwent regular clinical, cognitive, and metabolic assessments. Using Cox regression analyses we assessed selected premorbid and baseline potential predictors of time to relapse. Relapse was defined using operationally defined relapse criteria. In the primary analysis only neurological soft signs total score retained significance, with higher scores predicting shorter time to relapse (HR = 1.05, 95% CI = 1.01-1.10, p = .029). In a more detailed secondary analysis poorer social relationships predicted shorter time to relapse (HR = 0.85, 95% CI = 0.76-0.95, p = .003). Our predominantly negative findings suggest that many of the previously implicated risk factors for the time to relapse are mediated by non-adherence rather than having a direct effect on relapse-proneness. Neurological soft signs, and perhaps quality of life in social relationships appear to play a role and merit further investigation.

Neurological Soft Signs and Social Cognition in Patients with Schizophrenia: the Missing Link

Schizophrenia is a debilitating mental disorder characterised by a pronounced decline in mental, physical, and social functioning. Our study aims to investigate the relationship between the socio-cognitive and the subtle motor and sensory symptoms of schizophrenia, which are, respectively, represented by facial emotion recognition deficits (FERD) and neurological soft signs (NSS). Thus, we assessed 60 patients diagnosed with schizophrenia. FERD was measured with the “Averaged Karolinska Directed Emotional Faces” set, and NSS was assessed with the Neurological Evaluation Scale. A strong and significant negative correlation was found between the NSS total score and the FERD total score (r = –0.7, p < 0.001). There was also a significant negative correlation between several of the subscores of both instruments. The results show that impaired social cognition is significantly associated with soft neurological disturbances in patients suffering from schizophrenia. Taken together, this reinforces the notion that schizophrenia is characterised by dysfunction and disconnection of a complex cerebral network, which can probably be influenced by psychosocial and physical nonpharmacological therapeutic interventions.

Neurological soft signs in first episode psychosis among psychiatric hospital patients and its relationship with dimensions of psychopathology: A comparative study.

Neurological soft signs (NSS), as subtle, nonlocalising neurological abnormalities, are considered as the potential markers of psychosis. However, comparative studies of antipsychotic-naïve patients with first-episode psychosis (FEP) and first degree relatives (FDRs) are uncommon. We compared the prevalence and pattern of NSS in FEPs, their healthy FDRs and a healthy non-relatives' control group (HC), highlighted the relationship between NSS and psychopathology and proposed cut-off scores for prevalence studies. Two hundred and two participants per group were recruited. The FEPs were consecutive attendees; FDRs were accompanying caregivers; while the HC were from hospital staff. The Brief Psychiatric Rating Scale and the Neurological Evaluation Scale were used to assess psychopathology dimensions and NSS, respectively. Using an item score of two ('substantial impairment'), the prevalence of at least one NSS was: 91.5% (95% confidence interval [CI]: 86.7%-94.9%), 16.8% (95% CI: 11.8%-22.7%) and 6.5% (95% CI: 3.5%-10.9%), respectively, for FEP, FDRs and HC. FEPs were impaired in a broad range of signs. The noteworthy relationships were as follows: (i) a significant correlation between the negative symptoms' dimension versus number of NSS (r = 0.4), and NSS total score (r = 0.3), (ii) the anxiety/depression dimension correlated negatively with number of NSS (r = -0.3) and (iii) NSS cut across psychosis categories. We propose a cut-off score of ≥ 4 for the number of signs signifying probable impairment. The findings indicate that, subject to further studies, NSS could be regarded as a broader phenotype of neurologic dysfunction associated with psychosis proness.

Neurological soft signs and brain morphology in people living with HIV

Neurological soft signs (NSS) are a common feature of severe psychiatric disorders such as schizophrenia but are also prevalent in organic brain diseases like HIV-associated neurocognitive disorder (HAND) or Alzheimer’s disease. While distinct associations between NSS, neurocognition, and cerebral regions were demonstrated in schizophrenia, these associations still have to be elucidated in HIV. Therefore, we investigated 36 persons with HIV of whom 16 were neurocognitively healthy and 20 were diagnosed with HAND. NSS were assessed using the Heidelberg scale. NSS scores were correlated with gray matter (GM) using whole brain voxel-based morphometry. Results showed significantly elevated NSS in the HAND group when compared to the neurocognitively healthy with respect to NSS total score and the subscores “orientation” and “complex motor tasks”. While the two groups showed only minor, non-significant GM differences, higher NSS scores (subscales “motor coordination”, “orientation”) were significantly correlated with GM reduction in the right insula and cerebellum (FWE-corrected). Our results corroborate elevated NSS in HIV+ patients with HAND in contrast to cognitively unimpaired patients. In addition, cerebral correlates of NSS with GM reductions in insula and cerebellum were revealed. Taken together, NSS in this patient group could be considered a marker of cerebral damage and neurocognitive deficits.

Investigation of structural brain correlates of neurological soft signs in individuals at ultra-high risk for psychosis.

Increased severity of neurological soft signs (NSS) in schizophrenia have been associated with abnormal brain morphology in cerebello-thalamo-cortical structures, but it is unclear whether similar structures underlie NSS prior to the onset of psychosis. The present study investigated the relationship between severity of NSS and grey matter volume (GMV) in individuals at ultra-high risk for psychosis (UHR) stratified for later conversion to psychosis. Structural T1-weighted MRI scans were obtained from 56 antipsychotic-naïve UHR individuals and 35 healthy controls (HC). The UHR individuals had follow-up data (mean follow-up: 5.2years) to ascertain clinical outcome. Using whole-brain voxel-based morphometry, the relationship between NSS and GMV at baseline was assessed in UHR, HC, as well as individuals who later transitioned (UHR-P, n = 25) and did not transition (UHR-NP, n = 31) to psychosis. NSS total and subscale scores except motor coordination were significantly higher in UHR compared to HC. Higher signs were also found in UHR-P, but not UHR-NP. Total NSS was not associated with GMV in the whole sample or in each group. However, in UHR-P individuals, greater deficits in sensory integration was associated with lower GMV in the left cerebellum, right insula, and right middle frontal gyrus. In conclusion, NSS are present in UHR individuals, particularly those who later transitioned to a psychotic disorder. While these signs show little overall variation with GMV, the association of sensory integration deficits with lower GMV in UHR-P suggests that certain brain areas may be implicated in the development of specific neurological abnormalities in the psychosis prodrome.

Structural correlates of sensorimotor dysfunction in heavy cannabis users.

Sensorimotor dysfunction has been previously reported in persons with cannabis dependence. Such individuals can exhibit increased levels of neurological soft signs (NSS), particularly involving motor coordination and sensorimotor integration. Whether such abnormalities may also apply to non-dependent individuals with heavy cannabis use (HCU) is unknown, as much as the neural correlates underlying such deficits. In this study, we investigated associations between NSS and gray matter volume (GMV) in males with HCU and male controls. Twenty-four persons with HCU and 17 controls were examined using standardized assessment of NSS and structural magnetic resonance imaging (MRI) at 3 T. GMV was calculated using voxel-based morphometry algorithms provided by the Computational Anatomy Toolbox (CAT12). Individuals with HCU showed higher NSS total scores compared to controls. In particular, significant NSS-subdomain effects were found for "motor coordination" (MoCo), "complex motor tasks" (CoMT), and "hard signs" (HS) expression in HCU (p <0.05, Bonferroni-corrected). Compared to controls, persons with HCU showed significant NSS/GMV interactions in putamen and inferior frontal cortex (MoCo), right cerebellum (CoMT) and middle and superior frontal cortices, and bilateral precentral cortex and thalamus (HS). In between-group analyses, individuals with HCU showed lower GMV in the right anterior orbital and precentral gyrus, as well as higher GMV in the right superior frontal gyrus and left supplementary motor cortex compared to controls. The data support the notion of abnormal sensorimotor performance associated with HCU. The data also provide a neuromechanistic understanding of such deficits, particularly with respect to aberrant cortical-thalamic-cerebellar-cortical circuit.

Neurological Soft Signs and Brain Abnormalities in Schizophrenia: A Literature Review.

Neurological soft signs (NSS) are subtle neurological impairments in sensory integration, motor coordination, balance, and sequencing of complex motor acts. The prevalence of NSS is well over 50% in schizophrenic patients compared to about 5% in healthy controls. About 30% of schizophrenia patients are resistant to treatment. The main reason for not finding better pharmaceutical agents is the inability to elicit the underlying neurophysiological and neuroanatomical basis of schizophrenia. The most common NSS can be divided into three domains: motor coordination, sequencing of complex motor acts, and sensory integration. Here, the neuroimaging correlates of the abovementioned NSS are reviewed. Most of the studies found a negative correlation of NSS subs cores motor coordination and complex motor tasks with the cerebellum, inferior frontal gyrus, and postcentral gyrus. There was a negative correlation between cortical thickness and NSS total scores in the left paracentral lobule, precuneus, middle frontal cortex, right inferior temporal cortex, left/right superior parietal cortex. Instead of considering NSS as a mere trait or state markers, its active inclusion in patient management is required to improve patients' quality of life. Future studies on larger cohorts, combining different imaging modalities are needed to elucidate how these factors might relate to each other and contribute to NSS.

Neurological soft signs (NSS) and cognitive deficits in HIV associated neurocognitive disorder

Neurological soft signs (NSS) are frequently found in severe mental disorders, such as Alzheimer's disease, schizophrenia or HIV associated neurocognitive disorder (HAND) which includes asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND) and HIV-associated dementia. To characterize NSS in patients with HIV we examined them with respect to neuropsychological deficits typically found in the disorder.67 HIV + patients without a history of head trauma, opportunistic infections, severe psychiatric disorders or acute confounding comorbidities of the Central nervous system (CNS) were recruited. NSS and neuropsychological deficits were examined on the Heidelberg scale and the Cambridge Neuropsychological Test Automated Battery (CANTAB), respectively. Semantic and phonemic verbal fluency were additionally established.According to NIMH and NINDS criteria, 18 patients were diagnosed with ANI and 21 with MND, 28 showed no cognitive deficits. NSS total scores were significantly correlated with several cognitive domains and NSS subscales. These correlations were confirmed when motor performance was entered as a covariate.According to our findings, NSS in HIV positive patients are significantly correlated with deficits in a broad range of neuropsychological domains. Similar findings were reported in schizophrenia, emphasizing the transdiagnostic character of NSS and supporting NSS examination in screening HIV patients for HAND.

S202. PROXIMAL AND DISTAL FACTORS ASSOCIATED WITH CLOZAPINE EXPOSURE IN A SAMPLE OF TREATMENT RESISTANT AND TREATMENT RESPONSIVE SCHIZOPHRENIA PATIENTS

BackgroundClozapine is the gold standard for Treatment Resistant Schizophrenia (TRS) and its use is strongly recommended after failure of two/three antipsychotics. Nonetheless, prescribing trends do not appear to follow the global guidelines and switching to clozapine is often delayed or improper. Reasons for clozapine underuse are quite understood, whereas little is known on clozapine misuse. In fact, more stringent operative criteria to define TRS should be used in clinical practice, taking advantage of standardized assessment tools in order to avoid false TRS positive.In these perspectives, we studied the patterns of clozapine prescription in a sample of TRS and non-TRS patients, in order to identify psychopathological variables associated with lifetime exposure to clozapine.Methods198 consecutive patients have been screened for eligibility criteria from 2016 until 2019 at Treatment Resistant Psychosis Centre of the University of Naples “Federico II”. Only stabilized schizophrenic patients aged between 18 and 65 were enrolled. All relevant clinical-demographic data were recorded. TRS diagnosis was based on TRRIP working group operational criteria and clear pseudo-resistance factors were excluded. Patients were subdivided into two groups: those having received or currently under clozapine treatment (eCLZ) and those never treated by clozapine (nCLZ). Patients were assessed for psychotic symptoms (PANSS), cognitive performances (BACS), neurological soft signs (NES), functional capacity (UPSA), social functioning (PSP and SLOF scales), and severity of illness (CGI-S).ResultsAmong the patients included (92), eCLZ were 50 (54.3%), of which 20% being non-TRS. Compared to nCLZ, eCLZ had a significantly earlier age at onset, more hospitalizations, higher daily antipsychotic doses; eCLZ patients had significantly higher scores on the CGI-S, PANSS total, PANSS Negative, General Psychopathology and PAUSS subscale and, according to the Five Factor PANSS Model, higher score on Negative and Disorganization Factors; eCLZ had also more impaired Working Memory performances, higher NES Total score, lower PSP and all SLOF areas scores, except Area4.Then we use univariate and multivariate analysis to delineate predictors of clozapine exposure and to evaluate whether these factors may organize in proximal (independent) and distal (mediated) associations. We found five independently associated variables that mediate all the other ones: high antipsychotic doses, higher disease severity, suicide attempts, impaired working memory, more severe Stereotyped Thinking.DiscussionWhile it is expected that some TRS patients might not receive clozapine, the observation that non-TRS patients had been exposed to clozapine may surprise. A possible explanation may be the lack of systematized procedure to diagnose TRS, which is often merely coincident with a nonspecific lack of response to antipsychotics.Due to mediation analysis, we further gained insights into the hierarchy of these variables’ impact on clozapine prescription and we finally compose a complex network of proximal and distal factors predicting clozapine exposure in schizophrenic patients.The above-mentioned independent variables significantly associated with clozapine exposure let intend that eCLZ patients may belong to a subset of more severely ill ones, beyond reaching the response threshold.Earlier onset patients may suffer from a more severe disease, be more prone to suicide attempts, and less responsive to antipsychotics.This result needs to be replicated in wider samples, and this relevant therapeutic issue should be further debated in order to gather robust evidence to support or discourage clozapine off-label use and misuse.

Neurological soft signs (NSS) and brain morphology in patients with chronic schizophrenia and healthy controls.

Subtle abnormalities in sensory integration, motor coordination and sequencing of complex motor acts or neurological soft signs (NSS) are characteristic phenomena in patients with schizophrenia at any stage of the illness. Previous MRI studies in schizophrenia found NSS to be associated with cortical, thalamic and cerebellar changes. Since these studies mainly focused on first-episode or recent onset schizophrenia, the cerebral correlates of NSS in chronic schizophrenia remained rather unclear. 49 middle-aged patients with chronic schizophrenia with a mean duration of illness of 20.3 ± 14.0 years and 29 healthy subjects matched for age and sex were included. NSS were examined on the Heidelberg Scale and correlated to grey matter (GM) by using whole brain high resolution magnetic resonance imaging (3 Tesla) with SPM12/CAT12 analyses. As expected, NSS in patients were significantly (p≤0.001) elevated in contrast to healthy controls, a finding, which not only applied to NSS total score, but also to the respective subscales “motor coordination”, “sensory integration”, “complex motor tasks”, “right/left and spatial orientation” and “hard signs”. Within the patient group NSS total scores were significantly correlated to reduced GM in right lingual gyrus, left parahippocampal gyrus, left superior temporal gyrus, left thalamus (medial dorsal nucleus) and left posterior lobe of the cerebellum (declive). Respective negative associations could also be revealed for the subscales “motor coordination”, “complex motor tasks” and “right/left and spatial orientation”. These findings remained significant after FWE-correction for multiple comparisons and were confirmed when years of education, chlorpromazine-equivalents or variables indicating the severity of psychopathology were introduced as additional covariates. According to our results lingual, parahippocampal, superior temporal, inferior and middle frontal gyri, thalamus and cerebellum have to be considered as important sites of NSS in chronic schizophrenia. That these findings only applied for patients but not healthy controls may indicate a different pathogenesis of NSS.

Neurological soft signs (NSS) and gray matter volume (GMV) in first-episode psychosis: An analysis of NSS motor subscores

We aimed to study the correlations between gray matter volume and the motor subscores of NSS in first-episode psychosis patients with both, whole brain and region of interest analyses. The structural MRIs of 81 first-episode psychosis patients were analyzed by using voxel-based morphometry (VBM) for SPM. NSS were assessed using the Heidelberg scale. Significant decreases of gray matter volume were correlated to high NSS total scores and, more specifically, frontal, subcortical and cerebellar areas were significantly correlated with increased scores of the subscores Motor Coordination (MoCo) and Complex Motor Tasks (CMT). When applying a stricter statistical correction, only the frontal gyrus and caudate nucleus survived for MoCo; whereas the precentral and superior frontal gyri survived for CMT. When doing regional analyses, using as masks the structures deemed as significant by the whole brain analyses and applying the FWE-correction, the superior frontal gyrus, thalamus and caudate nucleus correlated negatively with MoCo; and the precentral and superior frontal gyri, thalamus and caudate nucleus showed inverse correlations with CMT. These results suggest that cerebral cortex, subcortical structures (thalamus and striatum) and cerebellum are inversely correlated to both motor NSS subscores, the first time a study describes this relationship for all the relevant structures simultaneously. For its part, ROI proves to be effective demonstrating that subcortical structures (thalamus and caudate) are the most affected by motor NSS.

Neurological soft signs in schizophrenia spectrum disorders are not confounded by current antipsychotic dosage

Neurological soft signs (NSS) have garnered increasing attention in psychiatric research on motor abnormalities in schizophrenia spectrum disorders (SSD). However, it remains unclear whether the assessment of NSS severity could have been confounded by current antipsychotic dosage. In this study, we recruited 105 patients with SSD that underwent a comprehensive motor assessment evaluating NSS and extrapyramidal motor symptoms (EPMS) by means of standardized instruments. Current antipsychotic dosage equivalence estimates were determined by the classical mean dose method (doses equivalent to 1 mg/d olanzapine). We used multiple regression analyses to describe the relationship between NSS, EPMS and antipsychotic medication. In line with our expectations, current antipsychotic dosage had no significant effects on NSS total score (p = 0.27), abnormal involuntary movements (p = 0.17), akathisia (p = 0.32) and parkinsonism (p = 0.26). Further, NSS total score had a significant effect on akathisia (p = 0.003) and parkinsonism (p = 0.0001, Bonferroni corr.), but only marginal effect on abnormal involuntary movements (p = 0.08). Our results support the notion that NSS are not significantly modulated by current antipsychotic dosage in SSD. The associations between NSS, akathisia and parkinsonism, as revealed by this study, support the genuine rather than medication-dependent origin of particular motor abnormalities in SSD.

Differential contributions of brainstem structures to neurological soft signs in first- and multiple-episode schizophrenia spectrum disorders

Neurological soft signs (NSS) are frequently found in patients with schizophrenia spectrum disorders (SSD) at any stage of the disease. Brainstem structures are crucial for motor control, integration of sensory input and coordination of automatic motor actions. It is unclear whether disease duration has an impact on NSS/brainstem volume relationships. We tested the hypothesis that volumes of brainstem structures differ between first-episode psychosis (FEP) and multiple-episodes psychosis (MEP) patients with SSD, and that alterations of these structures are associated with NSS. T1-weighted structural MRI data at 3 T were obtained from 92 right-handed SSD patients (27 FEP and 65 MEP). FreeSurfer vers. 6.0 was used for segmentation of brainstem structures including the medulla oblongata, pons, superior cerebellar pedunculus (SCP), and midbrain. Multiple regression analyses were used to describe the relationship between brainstem structures and distinct NSS subdomains. In FEP, pons volume had a significant effect on NSS total score (p = 0.001, Bonferroni corr.). Further, medulla oblongata (p = 0.001, Bonferroni corr.) and pons (p = 0.001, Bonferroni corr.) volumes had a significant effect on NSS motor coordination score. In MEP, significant associations between brainstem structures and NSS levels were not found. The present data support the notion that brainstem structures play an important role in the expression of NSS in SSD individuals with FEP, in contrast to individuals with MEP. Our study also emphasizes the need of better characterizing episode-specific brainstem correlates of NSS in SSD.

Evaluation of a few discrete clinical markers may predict categorization of actively symptomatic non-acute schizophrenia patients as treatment resistant or responders: A study by ROC curve analysis and multivariate analyses

Here, we used Receiver Operating Characteristic (ROC) curve analysis to determine whether clinical factors may aid predicting the categorization of schizophrenia patients as Treatment Resistant (TRS) or antipsychotic responsive schizophrenia (ARS). Patients with an established condition of TRS or ARS were assessed for: clinical presentation and course; neurological soft signs (NES); psychopathology by PANSS; cognitive performances; quality of life scale (QLS); functional capacity; social functioning (PSP and SLOF scales). In ROC curve analysis, significance indicated that the Area under curve (AUC) allowed distinguishing between TRS and ARS. Multivariate analyses were additionally used to provide independent predictive analysis. Multiple clinical variables showed significant AUCs. The largest significant AUCs were found for: NES total score; SLOF Area2; QLS subscale; antipsychotic doses. The highest sensitivity was found for NES total score, the highest specificity for previous hospitalizations. The highest Odds Ratio of being included within the TRS category were found for: NES total score (7.5); QLS total score (5.49); and previous hospitalizations (4.76). This same circumscribed group of variables was also found to be predictive of TRS when adopting stepwise logistic regression or discriminant analysis. We concluded that the evaluation of few clinical factors may provide reliable and accurate predictions on whether one schizophrenia patient may be categorized as a TRS.

F175. NEUROLOGICAL SOFT SIGNS (NSS) AND BRAIN MORPHOLOGY IN PATIENTS WITH CHRONIC SCHIZOPHRENIA AND HEALTHY CONTROLS

BackgroundSubtle abnormalities in sensory integration, motor coordination and sequencing of complex motor acts or neurological soft signs (NSS) are a characteristic phenomenon in patients with schizophrenia at any stage of the illness. Previous MRI studies in schizophrenia have shown that NSS are associated with abnormal cortical, thalamic and cerebellar structure. However, these studies mainly focused on first-episode or recent onset schizophrenia and the respective correlates between brain structure and NSS in patients with a chronic course of the disorder remain rather unclear.Methods49 middle-aged patients with chronic schizophrenia with a mean duration of illness of 20.3 ± 14.0 years and 29 healthy subjects matched for age and sex were included. NSS were examined on the Heidelberg Scale and correlated to grey matter by using whole brain high resolution magnetic resonance imaging (3 Tesla) with SPM12 analyses.ResultsAs expected, NSS in patients were significantly elevated in contrast to healthy controls, a finding, which not only applied to NSS sumscore, but also to the respective subscores motor coordination, sensory integration, complex motor tasks, right/left and spatial orientation and hard signs (p≤0.001).Patients and healthy controls differed referring to right inferior frontal gyrus and left parahippocampal gyrus, with patients showing significantly reduced gray matter volumes, respectively. Within the patient group NSS total score was significantly correlated to reduced grey matter in right occipital lobe, left parahippocampal gyrus, left superior temporal gyrus, left thalamus (medial dorsal nucleus) and left posterior lobe of the cerebellum (declive). The respective findings remained significant after FDR correction for multiple comparisons (k=100 voxels). These results were confirmed when chlorpromazine (CPZ)-equivalents were introduced as additional covariate; moreover, no significant correlates arose between NSS and CPZ-equivalents. In the control group, VBM revealed that higher NSS total scores were significantly correlated with volume of right lentiform nucleus (medial globus pallidus).DiscussionOur study leads further support to the model of ‘cognitive dysmetria’ with a disrupted cortico-cerebellar-thalamic-cortical circuit in schizophrenia. This interpretation is also maintained by a different correlational pattern in our control group. Furthermore, the middle temporal/parahippocampal region may correspond to reduced mnestic functions, which are – besides elevated NSS – consistently reported to be impaired in patients with a chronic course of the disorder.

Neurological Soft Signs in Schizophrenia: An Update on the State- versus Trait-Perspective.

Neurological soft signs (NSS) represent minor neurological signs, which indicate non-specific cerebral dysfunction. In schizophrenia, their presence has been documented extensively across all stages of the disease. Until recently, NSS were considered an endophenotype or a trait phenomenon. During the past years, however, researchers report fluctuations of the NSS scores. To further clarify the question whether NSS exhibit state or trait components or both, studies that have investigated NSS longitudinally were reviewed. Studies which have assessed NSS longitudinally in adults suffering from schizophrenia, were searched for. The time frame was January 1966 to June 2017. Studies on teenagers were excluded because of interferences between brain maturation and pathology. Twenty-nine follow-up studies were identified. They included patients during different stages of their illness and mainly used established instruments for NSS assessment. Patients with a first episode or a remitting course predominantly show a decrease of NSS over time, whereas a worsening of NSS can be found in the chronically ill. It was shown that change of NSS total scores over time is predominantly caused by motor system subscales and to a lesser extent by sensory integration scales. With respect to medication, the majority of studies agree on a relationship between medication response and improvement of NSS while the type of antipsychotic does not seem to play a major role. Moreover, where information on side-effects is given, it does not favor a strong relationship with NSS. However, NSS seem to correlate with negative and cognitive symptoms. Studies manifest a conformity regarding the presence of NSS in schizophrenia patients on the one hand. On the other hand, fluctuations of NSS scores have been widely described in subgroups. Taken together results strongly support a state-trait dichotomy of NSS. Thus, the usage of NSS as an endophenotype has to be called into question.

Neurological soft signs in euthymic bipolar I patients: A comparative study with healthy siblings and controls

Neurological Soft Signs (NSS) are endophenotypic markers widely studied in schizophrenia and remain poorly evaluated in bipolar disorder. The aims of this paper were to determine the prevalence and scores of NSS in bipolar I patients, compared to healthy siblings and controls and to explore correlations with socio-demographic and clinical features of patients. This was a case-control study comparing 92 euthymic bipolar I patients, 44 of their healthy siblings and 60 control subjects. The neurological assessment was performed through the NSS scale validated by Krebs et al. (2000). Bipolar I patients were also assessed with the Bech-Rafaelsen Mania Scale (MAS), the Hamilton Depression Rating Scale (HDRS) and the Global Assessment of Functioning (GAF). The raters were not blinded to groups. The prevalence and the total score of NSS were significantly higher in bipolar I patients compared to their healthy siblings and controls. The sibling group had significantly higher NSS prevalence and total score than controls. No correlation was found between NSS total score and socio-demographic and clinical features of patients, except a negative correlation with the school level and the GAF score. In conclusion, bipolar I patients have motor and sensory signs, which are unrelated to their clinical features.

Nerological Soft Signs in HIV-associated Neurocognitive Disorder: a Clinical Marker?

Introduction With the introduction of antiretroviral treatment, the survival rates of Human Immunodeficiency virus (HIV) patients have improved significantly. However, the incidence of HIV- associated neurocognitive disorders (HAND) gained importance and represents actually a significant public health problem. Neurological soft signs (NSS) refers to subtle neurological abnormalities in motor and sensory performance. The presence of these symptoms has been widely described in patients with mental diseases like Schizophrenia or Alzheimer’s Disease, but have not been studied in HAND despite its known subcortical physiopathology. Objectives To study the prevalence HAND in a Chilean cohort of HIV patients and describe its association to NSS. Methods HIV patients without history of head injury trauma or opportunistic infections of the CNS were recruited from the HIV clinic, underwent a thorough clinical interview and neuropsychological testing. Healthy controls were recruited from the community. All participants were assessed with the Heidelberger NSS scale. HAND was diagnosed using NIMH and NINDS criteria. Results Until now, 35 HIV+ patients and 18 controls completed the described assessment. 11 patients were cognitive healthy, 11 with Asymptomatic Neurocognitive Impairment (ANI) and 13 with Mild Neurocognitive Disorder (MND). NSS total score differed significantly between groups (F= 2,92 (DF=3), p ANI, MND and Cognitive healthy HIV>MND. Discussion Our data supports the use of NSS as a marker of HAND. It should be considered in the clinical examination of HIV patients.

Neurological abnormalities in recent-onset schizophrenia and asperger-syndrome.

Background: Neurological abnormalities including a variety of subtle deficits such as discrete impairments in sensory integration, motor coordination (MOCO), and sequencing of complex motor acts are frequently found in patients with schizophrenia (SZ) and commonly referred to as neurological soft signs (NSS). Asperger-syndrome (AS) is characterized by sensory-motor difficulties as well. However, the question whether the two disorders share a common or a disease-specific pattern of NSS remains unresolved.Method: A total of 78 age- and education-matched participants [26 patients with recent-onset SZ, 26 individuals with AS, and 26 healthy controls (HC)] were recruited for the study. Analyses of covariance (ANCOVAs), with age, years of education, and medication included as covariates, were used to examine group differences on total NSS and the five subscale scores. Discriminant analyses were employed to identify the NSS subscales that maximally discriminate between the three groups.Results: Significant differences among the three groups were found in NSS total score and on the five NSS subscales. The clinical groups differed significantly in the NSS subscale MOCO. The correct discriminant rate between patients with SZ and individuals with AS was 61.5%. The correct discriminant rate was 92.3% between individuals with AS and HC, and 80.8% between SZ patients and HC, respectively.Conclusion: Our findings provide new evidence for the presence of NSS in AS and lend further support to previously reported difficulties in movement control in this disorder. According to the present results, SZ and AS seem to be characterized by both quantitative and qualitative NSS expression.

Signes neurologiques mineurs dans la schizophrénie précoce

Neurological soft signs (NSS) are subtle neurological abnormalities that cannot be linked to the achievement of a specific region of the central nervous system and which are not part of a particular neurological syndrome. These signs are observed in the case of diseases supporting the neurodevelopmental model such as schizophrenia in general and its early form defined notably by an age of onset of less than 18 years. Indeed, the NSS belong to a set of clinical, cognitive, electrophysiological and neuroanatomical markers reflecting neurodevelopmental brain abnormalities in patients with schizophrenia. The objectives of our study were to determine the prevalence, the scores, and the nature of neurological soft signs (NSS) in adolescent patients suffering from early onset schizophrenia diagnosis in comparison to healthy controls, and to explore the correlations between NSS and the demographic, clinical and therapeutic features of these patients. Twelve adolescents were recruited in the Child Psychiatry Department at the Razi Hospital (Tunisia), with the diagnosis of schizophrenia according to the DSM-IV supplemented by the Kiddie SAD PL. They were matched by age and educational level with twelve healthy controls without psychiatric family or personal history. The clinical status of the patients was assessed using the Positive and Negative Syndrome Scale (PANSS). Neurological soft signs (NSS) were rated with the Neurological Soft Signs Examination (NSSE) by Krebs et al. (2000) for the two groups. This scale is composed of 23 items exploring motor coordination, motor integrative function, sensory integration, involuntary movements and quality of lateralization. The mean age of our population was 14.7 years. The average age of onset of the disease was 12.2 years. The sex-ratio was 1.4. Educational level was 7.4 years. The PANSS mean total score was 74.3. The mean daily dose, in chlorpromazine equivalents, was 523.9 mg/day. Four patients received a strict monotherapy of antipsychotics, while the other patients were receiving an association of two neuroleptics. The prevalence of NSS was 100% (cut-off point=11) with a mean total score of 29.3±4.1. The highest score was for the motor coordination (10.1). As for the control group, the mean total score was 7±1.3. A highly significant difference was found between patients and controls for all sub-scores of NSS. Negative correlations were found in patients, between age and neurological soft signs total score (P=0.05; r=-0.57) and also with sensory integration score (P=0.04; r=-0.58). The NSS total score was also correlated with low educational level (P=0.03; r=-0.61). There was no correlation between neurological soft signs scores and PANSS scores or the daily dose of antipsychotics. The prevalence and NSS scores are high among young people with early onset schizophrenia diagnosis illustrating the existence of structural abnormalities of the brain, themselves consequences of early neurodevelopmental disturbances, which would support the neurodevelopmental hypothesis concerning this pathology.