The Brief Psychiatric Rating Scale (version 4.0) factorial structure and its sensitivity in the treatment of outpatients with unipolar depression.

The 24-item Brief Psychiatric Rating Scale (BPRS, version 4.0) enables the rater to measure psychopathology severity. Still, little is known about the BPRS's reliability and validity outside of the psychosis spectrum. The aim of this study was to examine the factorial structure and sensitivity to change of the BPRS in patients with unipolar depression. Two hundred and forty outpatients with unipolar depression were administered the 24-item BPRS. Assessments were conducted at intake and at post-treatment in a Crisis Intervention Centre. An exploratory factor analysis of the 24-item BPRS produced a six-factor solution labelled "Mood disturbance", "Reality distortion", "Activation", "Apathy", "Disorganization", and "Somatization". The reduction of the total BPRS score and dimensional scores, except for "Activation", indicates that the 24-item BPRS is sensitive to change as shown in patients that appeared to have benefited from crisis treatment. The findings suggest that the 24-item BPRS could be a useful instrument to measure symptom severity and change in symptom status in outpatients presenting with unipolar depression.

Effectiveness of anti-psychotics and related drugs in the Huntington French-speaking group cohort.

PURPOSE: Huntington's disease is a rare condition. Patients are commonly treated with antipsychotics and tetrabenazine. The evidence of their effect on disease progression is limited and no comparative study between these drugs has been conducted. We therefore compared the effectiveness of antipsychotics on disease progression. METHODS: 956 patients from the Huntington French Speaking Group were followed for up to 8 years between 2002 and 2010. The effectiveness of treatments was assessed using Unified Huntington's Disease Rating Scale (UHDRS) scores and then compared using a mixed model adjusted on a multiple propensity score. RESULTS: 63% of patients were treated with antipsychotics during the survey period. The most commonly prescribed medications were dibenzodiazepines (38%), risperidone (13%), tetrabenazine (12%) and benzamides (12%). There was no difference between treatments on the motor and behavioural declines observed, after taking the patient profiles at the start of the drug prescription into account. In contrast, the functional decline was lower in the dibenzodiazepine group than the other antipsychotic groups (Total Functional Capacity: 0.41 ± 0.17 units per year vs. risperidone and 0.54 ± 0.19 vs. tetrabenazine, both p<0.05). Benzamides were less effective than other antipsychotics on cognitive evolution (Stroop interference, Stroop color and Literal fluency: p<0.05). CONCLUSIONS: Antipsychotics are widely used to treat patients with Huntington's disease. Although differences in motor or behavioural profiles between patients according to the antipsychotics used were small, there were differences in drug effectiveness on the evolution of functional and cognitive scores.

Recombinant human insulin-like growth factor I (rhIGF-I) for the treatment of amyotrophic lateral sclerosis/motor neuron disease.

BACKGROUND: Recombinant human insulin-like growth factor I (rhIGF-I) is a possible disease modifying therapy for amyotrophic lateral sclerosis (ALS, which is also known as motor neuron disease (MND)). OBJECTIVES: To examine the efficacy of rhIGF-I in affecting disease progression, impact on measures of functional health status, prolonging survival and delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival in ALS. Occurrence of adverse events was also reviewed. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (21 November 2011), CENTRAL (2011, Issue 4), MEDLINE (January 1966 to November 2011) and EMBASE (January 1980 to November 2011) and sought information from the authors of randomised clinical trials and manufacturers of rhIGF-I. SELECTION CRITERIA: We considered all randomised controlled clinical trials involving rhIGF-I treatment of adults with definite or probable ALS according to the El Escorial Criteria. The primary outcome measure was change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score after nine months of treatment and secondary outcome measures were change in AALSRS at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life (Sickness Impact Profile scale), survival and adverse events. DATA COLLECTION AND ANALYSIS: Each author independently graded the risk of bias in the included studies. The lead author extracted data and the other authors checked them. We generated some missing data by making ruler measurements of data in published graphs. We collected data about adverse events from the included trials. MAIN RESULTS: We identified three randomised controlled trials (RCTs) of rhIGF-I, involving 779 participants, for inclusion in the analysis. In a European trial (183 participants) the mean difference (MD) in change in AALSRS total score after nine months was -3.30 (95% confidence interval (CI) -8.68 to 2.08). In a North American trial (266 participants), the MD after nine months was -6.00 (95% CI -10.99 to -1.01). The combined analysis from both RCTs showed a MD after nine months of -4.75 (95% CI -8.41 to -1.09), a significant difference in favour of the treated group. The secondary outcome measures showed non-significant trends favouring rhIGF-I. There was an increased risk of injection site reactions with rhIGF-I (risk ratio 1.26, 95% CI 1.04 to 1.54). . A second North American trial (330 participants) used a novel primary end point involving manual muscle strength testing. No differences were demonstrated between the treated and placebo groups in this study. All three trials were at high risk of bias. AUTHORS' CONCLUSIONS: Meta-analysis revealed a significant difference in favour of rhIGF-I treatment; however, the quality of the evidence from the two included trials was low. A third study showed no difference between treatment and placebo. There is no evidence for increase in survival with IGF1. All three included trials were at high risk of bias.

Levodopa in the treatment of Parkinson's disease: an old drug still going strong.

After more than 40 years of clinical use, levodopa (LD) remains the gold standard of symptomatic efficacy in the drug treatment of Parkinson's disease (PD). Compared with other available dopaminergic therapies, dopamine replacement with LD is associated with the greatest improvement in motor function. Long-term treatment with LD is, however, often complicated by the development of various types of motor response oscillations over the day, as well as drug-induced dyskinesias. Motor fluctuations can be improved by the addition of drugs such as entacapone or monoamine oxidase inhibitors, which extend the half-life of levodopa or dopamine, respectively. However, dyskinesia control still represents a major challenge. As a result, many neurologists have become cautious when prescribing therapy with LD. This review summarizes the available evidence regarding the use of LD to treat PD and will also address the issue of LD delivery as a critical factor for the drug's propensity to induce motor complications.

Effect on mood of subthalamic DBS for Parkinson's disease: a consecutive series of 24 patients

A series of 24 consecutive PD patients were prospectively studied prior to and within 6 months postoperatively for mood, motor, and cognitive status to investigate the effects on mood of subthalamic deep brain stimulation (DBS) in PD. In six patients (25%), mood state worsened significantly, and three were transiently suicidal despite clear motor improvement. Caregivers and patients should be educated about the potential impact of this neurosurgical procedure on mood.

Neuropsychiatrie de l'épilepsie, des accidents vasculaires cérébraux, de la maladie de Parkinson et de la sclérose en plaques [Neuropsychiatry of epilepsy, stroke, Parkinson's disease and multiple sclerosis]

L'étude du comportement au sens large fait partie intégrante de l'examen neurologique classique. Cet article présente une revue des manifestations comportementales et thymiques dans l'épilepsie, l'accident vasculaire cérébral, la maladie de Parkinson et la sclérose en plaques. The assessement of behavior is common part of the neurological examination. This article reviews the behavioral and mood manifestations in four classical syndroms: Epilepsy, stroke, Parkinson's disease and multiple sclerosis

Small vascular and Alzheimer disease-related pathologic determinants of dementia in the oldest-old.

The relative contributions of Alzheimer disease (AD) and vascular lesion burden to the occurrence of cognitive decline are more difficult to define in the oldest-old than they are in younger cohorts. To address this issue, we examined 93 prospectively documented autopsy cases from 90 to 103 years with various degrees of AD lesions, lacunes, and microvascular pathology. Cognitive assessment was performed prospectively using the Clinical Dementia Rating scale. Neuropathologic evaluation included the Braak neurofibrillary tangle (NFT) and β-amyloid (Aβ) protein deposition staging and bilateral semiquantitative assessment of vascular lesions. Statistics included regression models and receiver operating characteristic analyses. Braak NFTs, Aβ deposition, and cortical microinfarcts (CMIs) predicted 30% of Clinical Dementia Rating variability and 49% of the presence of dementia. Braak NFT and CMI thresholds yielded 0.82 sensitivity, 0.91 specificity, and 0.84 correct classification rates for dementia. Using these threshold values, we could distinguish 3 groups of demented cases and propose criteria for neuropathologic definition of mixed dementia, pure vascular dementia, and AD in very old age. Braak NFT staging and severity of CMI allow for defining most of demented cases in the oldest-old. Most importantly, single cutoff scores for these variables that could be used in the future to formulate neuropathologic criteria for mixed dementia in this age group were identified.

Ambulatory monitoring of physical activities in patients with Parkinson's disease.

A new ambulatory method of monitoring physical activities in Parkinson's disease (PD) patients is proposed based on a portable data-logger with three body-fixed inertial sensors. A group of ten PD patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) and ten normal control subjects followed a protocol of typical daily activities and the whole period of the measurement was recorded by video. Walking periods were recognized using two sensors on shanks and lying periods were detected using a sensor on trunk. By calculating kinematics features of the trunk movements during the transitions between sitting and standing postures and using a statistical classifier, sit-to-stand (SiSt) and stand-to-sit (StSi) transitions were detected and separated from other body movements. Finally, a fuzzy classifier used this information to detect periods of sitting and standing. The proposed method showed a high sensitivity and specificity for the detection of basic body postures allocations: sitting, standing, lying, and walking periods, both in PD patients and healthy subjects. We found significant differences in parameters related to SiSt and StSi transitions between PD patients and controls and also between PD patients with and without STN-DBS turned on. We concluded that our method provides a simple, accurate, and effective means to objectively quantify physical activities in both normal and PD patients and may prove useful to assess the level of motor functions in the latter.

Molecular chaperones and associated cellular clearance mechanisms against toxic protein conformers in Parkinson's disease.

Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder marked by the loss of dopaminergic neurons (in particular in the substantia nigra) causing severe impairment of movement coordination and locomotion, associated with the accumulation of aggregated α-synuclein (α-Syn) into proteinaceous inclusions named Lewy bodies. Various early forms of misfolded α-Syn oligomers are cytotoxic. Their formation is favored by mutations and external factors, such as heavy metals, pesticides, trauma-related oxidative stress and heat shock. Here, we discuss the role of several complementing cellular defense mechanisms that may counteract PD pathogenesis, especially in youth, and whose effectiveness decreases with age. Particular emphasis is given to the 'holdase' and 'unfoldase' molecular chaperones that provide cells with potent means to neutralize and scavenge toxic protein conformers. Because chaperones can specifically recognize misfolded proteins, they are key specificity factors for other cellular defenses, such as proteolysis by the proteasome and autophagy. The efficiency of the cellular defenses decreases in stressed or aging neurons, leading to neuroinflammation, apoptosis and tissue loss. Thus, drugs that can upregulate the molecular chaperones, the ubiquitin-proteasome system and autophagy in brain tissues are promising avenues for therapies against PD and other mutation-, stress- or age-dependent protein-misfolding diseases.

Sub-acute delayed failure of subthalamic DBS in Parkinson's disease: the role of micro-lesion effect.

OBJECTIVE: To study delayed failure after subthalamic nucleus (STN) deep brain stimulation in Parkinson's disease (PD) patients. METHODS: Out of 56 consecutive bilaterally STN-implanted PD patients, we selected subjects who, after initial clinical improvement (1 month after surgery), lost benefit (delayed failure, DF). RESULTS: Five patients developed sub-acutely severe gait disorders (DF). In 4/5 DF patients, a micro-lesion effect, defined as improvement without stimulation, was observed; immediate post-operative MRI demonstrated electrode located above or behind to the STN. CONCLUSIONS: Patients presenting micro-lesion effect should be carefully monitored, as this phenomenon can mask electrodes misplacement and evolution in DF

Predicting clinical scores from magnetic resonance scans in Alzheimer's disease.

Machine learning and pattern recognition methods have been used to diagnose Alzheimer's disease (AD) and mild cognitive impairment (MCI) from individual MRI scans. Another application of such methods is to predict clinical scores from individual scans. Using relevance vector regression (RVR), we predicted individuals' performances on established tests from their MRI T1 weighted image in two independent data sets. From Mayo Clinic, 73 probable AD patients and 91 cognitively normal (CN) controls completed the Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), and Auditory Verbal Learning Test (AVLT) within 3months of their scan. Baseline MRI's from the Alzheimer's disease Neuroimaging Initiative (ADNI) comprised the other data set; 113 AD, 351 MCI, and 122 CN subjects completed the MMSE and Alzheimer's Disease Assessment Scale-Cognitive subtest (ADAS-cog) and 39 AD, 92 MCI, and 32 CN ADNI subjects completed MMSE, ADAS-cog, and AVLT. Predicted and actual clinical scores were highly correlated for the MMSE, DRS, and ADAS-cog tests (P<0.0001). Training with one data set and testing with another demonstrated stability between data sets. DRS, MMSE, and ADAS-Cog correlated better than AVLT with whole brain grey matter changes associated with AD. This result underscores their utility for screening and tracking disease. RVR offers a novel way to measure interactions between structural changes and neuropsychological tests beyond that of univariate methods. In clinical practice, we envision using RVR to aid in diagnosis and predict clinical outcome.

Les troubles psychiatriques des patients âgés avec une maladie de Parkinson et leurs traitements [Psychiatric disorders in elderly patients with Parkinson's disease and their treatments].

Parkinson's disease (PD) is a neuropsychiatric disorder. During the course of PD, most patients develop at least one psychiatric syndrome. Depression is the most frequent disorder and affects nearly half of all patients. The use of an increasing number of new drugs, in particular the dopaminergic agents, puts these patients at risk of developing both delirium and psychosis. This article summarizes the different psychiatric syndromes seen in PD and gives an account of the various treatment possibilities.