Pyramidal Symptoms Research Articles

A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia

BackgroundAntipsychotic medications often have a variety of side effects, however, it is not well understood how the presence of specific side effects correlate with adherence in a real-world setting. The aim of the current study was to examine the relationship between these variables among community-dwelling patients with schizophrenia.MethodsData were analyzed from a 2007-2008 nationwide survey of adults who self-reported a diagnosis of schizophrenia and were currently using an antipsychotic medication (N = 876). The presence of side effects was defined as those in which the patient reported they were at least "somewhat bothered". Adherence was defined as a score of zero on the Morisky Medication Adherence Scale. To assess the relationship between side effects and adherence, individual logistic regression models were fitted for each side effect controlling for patient characteristics. A single logistic regression model assessed the relationship between side effect clusters and adherence. The relationships between adherence and health resource use were also examined.ResultsA majority of patients reported experiencing at least one side effect due to their medication (86.19%). Only 42.5% reported complete adherence. Most side effects were associated with a significantly reduced likelihood of adherence. When grouped as side effect clusters in a single model, extra pyramidal symptoms (EPS)/agitation (odds ratio (OR) = 0.57, p = 0.0007), sedation/cognition (OR = 0.70, p = 0.033), prolactin/endocrine (OR = 0.69, p = 0.0342), and metabolic side effects (OR = 0.64, p = 0.0079) were all significantly related with lower rates of adherence. Those who reported complete adherence to their medication were significantly less likely to report a hospitalization for a mental health reason (OR = 0.51, p = 0.0006), a hospitalization for a non-mental health reason (OR = 0.43, p = 0.0002), and an emergency room (ER) visit for a mental health reason (OR = 0.60, p = 0.008).ConclusionsAmong patients with schizophrenia, medication side effects are highly prevalent and significantly associated with medication nonadherence. Nonadherence is significantly associated with increased healthcare resource use. Prevention, identification, and effective management of medication-induced side effects are important to maximize adherence and reduce health resource use in schizophrenia.

P-1112 - Attitudes of french psychiatrists toward antipsychotic depot medication in schizophrenia

Despite a favorable pharmacological rational, the prescription of antipsychotics depot formulation in patients with schizophrenia is low. The goal of our study was to assess the attitudes of French psychiatrists toward the use of depot antipsychotics in patients with schizophrenia. 113 french psychiatrists were interviewed at a congress of psychiatry, using a questionnaire to identify psychiatrists attitudes influencing the use of long-acting injectable antipsychotics (LAI) in schizophrenia. Multidimensional and cluster analyses were used to detect correlations. According to data compiled by the german team of S. Heres (2008), two clusters of factors specific to the patient for the prescription of antipsychotic depot, have been identified: the cluster “high level of therapeutic alliance and high level of insight” on the one hand and the cluster “poor compliance to oral therapy and high number of relapses in the past” on the other. The most important factor against the use of LAI antipsychotics is a sufficient estimated compliance with the oral formulation. For first-generation LAI, the main factor is the risk of extra pyramidal symptoms and for second-generation LAI, it is the unavailability of the equivalent of oral formulation. Among the reasons influencing the prescription of LAI antipsychotic, history of poor adherence to oral therapy is important. In contrast, the highlighting of a profile of patients with a high level of insight and a high level of therapeutic alliance, confirms the value of these forms beyond the traditional profile of non-adherent.

Unilateral tremor induced by risperidone in a patient with acute mania: Vitamin B12 deficiency as possible mediating factor

Identification and management of drug-induced movement disorders is a clinical challenge, more so when the clinical presentation is atypical. A young male with acute mania was under treatment with sodium valproate and risperidone. He developed tremors of right hand and neck. These were present at rest and exacerbated by mental activity, when under observation and during voluntarily initiated activity. There were no associated extra pyramidal symptoms or cerebellar signs. Investigations for other common causes of tremors did not reveal any evidence except for low value of serum vitamin B12 levels. The tremors persisted after the withdrawal of valproate, but resolved following the withdrawal of risperidone. It is a common dictum that drug-induced tremors are bilateral. This may not be true always as we found out in our case. These movements were probably induced by risperidone. This atypical presentation could be due to concurrent use of valproate and low serum vitamin B12 levels.

Leukodystrophy with a cerebellar cystic aspect and intracranial atherosclerosis: an atypical presentation of cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis (CTX, MIM #213700) is a rare autosomal recessive lipid storage disease where the clinical signs include juvenile cataracts, tendon xanthomas, intractable diarrhea, ataxia, and dementia. Diagnosis is based on increased levels of serum cholestanol and mitochondrial sterol 27-hydroxylase gene (CYP27) mutations. This report describes atypical MRI patterns in a late-onset patient. A 59-year-old woman, free of neurological symptoms up to the age of 50, including absence of mental retardation, presented with a 9-year history of progressive unsteadiness and cognitive impairment. Medical history consisted of a bilateral cataract surgically treated at the age of 47 and diarrhea with weight loss since her early 50s. Clinical examination revealed cerebellar ataxia, pyramidal, extrapyramidal (akinesia and rigidity) and pseudobulbar symptoms, dementia (Mini Mental Status 13/30) without tendon xanthomas. Brain CT scan showed spontaneous hyperdensity and increased diameter of the basilar artery (Fig. 1a). Brain MRI found hyperintensities on T2 and FLAIR sequences, involving middle cerebellar peduncles, pons, internal capsules, corpus callosum, and periventricular areas (Fig. 1b, c), without gadolinium-enhancement on T1 sequences. In addition, severe cerebellar atrophy and extensive hypointense signal of both cerebellar hemispheres were seen on T1 and FLAIR sequences (Fig. 1d–f). T2* sequences showed microbleeds in the cerebellar white matter and left thalamus (Fig. 1g). Extensive research of metabolic causes of leukodystrophy was negative, except for plasma 7 dehydrocholesterol (13.27 mol/l, normal \3 mol/l) and cholestanol levels (31.9 mol/l, normal \6.2 mol/l), which were increased.

“Preclinical” MSA in definite Creutzfeldt‐Jakob disease

Multiple system atrophy (MSA) is a sporadic alpha-synucleinopathy clinically characterized by variable degrees of parkinsonism, cerebellar ataxia and autonomic dysfunction. The histopathological hallmark of MSA is glial cytoplasmic inclusion (GCI). It is considered to represent the earliest stage of the degenerative process in MSA and to precede neuronal degeneration. Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal, rapidly progressive dementia generally associated with ataxia, pyramidal and extrapyramidal symptoms and myoclonus. Definite diagnosis needs neuropathological demonstration of variable degrees of spongiform degeneration of neuropil, neuronal loss, astro- and microgliosis, and the presence of abnormal deposits of the misfolded prion protein PrP(res) . Both diseases, CJD and MSA are infrequent among neurodegenerative diseases. In the present report we describe clinical and neuropathological findings of a previously healthy 64-year-old woman who developed symptoms of classical CJD. At post mortem examination, the brain showed in addition to classical methionine/methionine PrP(res) type 1 (MM1) sCJD changes and moderate Alzheimer-type pathology, features of "preclinical" MSA with minimal histopathological changes. These were characterized by discrete amounts of alpha-synuclein immunoreacive glial cytoplasmic inclusions in the striato-nigral system, isolated intraneuronal inclusions in pigmented neurons of the substantia nigra, as well as some vermiform intranuclear inclusions. To our knowledge, this is the first report on the coexistence of definite sCJD and "minimal changes" MSA in the same patient.

Restless Legs Syndrome in Multiple Sclerosis

Aims: Multiple sclerosis (MS) is a demyelinating neurodegenerative inflammatory autoimmune disease. Restless legs syndrome (RLS) is characterized as a strong urge to move the legs to stop abnormal sensations there. In this study, we aimed to investigate whether or not the increased RLS frequency seen in MS could be associated with depression and fatigue. Methods: The study involved 98 patients with definite MS and 129 healthy volunteers. The Beck Depression Inventory and Fatigue Severity Scale were used to assess all participants. The patients and the healthy volunteers were examined for RLS according to the criteria of the International Restless Legs Syndrome Study Group. Results: When the factors related to RLS in MS were evaluated, there were significant relationships found among age, type of MS, pyramidal symptoms, intestinal and bladder symptoms, number of lesions in MR, depression, and fatigue. Risk factors for RLS were also seen more frequently in the MS group than in the healthy volunteers. Conclusion: RLS was seen 2.55 times more frequently in patients with MS than in the control group. This was due to the existence of numerous factors rather than a single factor – including depression and fatigue.

Molecular properties affecting fast dissociation from the D 2 receptor

Dopamine D 2 receptor antagonism is the foundation of antipsychotic treatment. Antipsychotic agents vary in how fast they dissociate from the D 2 receptors. It has been proposed that the liability to exhibit side effects such as extra pyramidal symptoms may be the result of a slow rate of dissociation. Compounds with a faster rate of dissociation, while still blocking efficiently the D 2 receptors, will subsequently respond better to physiological surges in dopamine transmission. Therefore, work in our laboratories has focussed on identifying fast dissociating and selective D 2 antagonists. Biological screening was performed to measure the affinity and extent of dissociation for a large dataset of over 1800 D 2 antagonists. Subsequent univariate and multivariate statistical analysis revealed the molecular properties which differentiate fast and slow dissociating compounds. It is shown that faster dissociating antagonists are less lipophilic and have lower molecular weight. There was a clear and expected inverse relationship with extent of dissociation and binding affinity with more potent compounds tending to be slower dissociating. However, within a range of comparable affinity both fast and slow dissociating compounds were identified. After de-correlating affinity and dissociation the analysis revealed the important descriptors.

MAPT H1 haplotype is a risk factor for essential tremor and multiple system atrophy

Mutations in the microtubule-associated protein tau gene ( MAPT ) cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17).1 In addition, the major common MAPT- containing H1 haplotype is associated with increased risk for 2 parkinsonian disorders: progressive supranuclear palsy (PSP) characterized by 4-repeat tau pathology and Parkinson disease (PD) with α-synuclein pathology.2,3 However, the role of MAPT variation in other disorders with similar pathology or disease phenotype is unclear. We investigated the frequency of the MAPT H1 haplotype in both essential tremor (ET) and multiple system atrophy (MSA). ET is the most common movement disorder, and prior evidence has indicated a common link between ET and PD from clinical, epidemiologic, and pathologic studies as well as some reports of brainstem Lewy bodies at autopsy in patients with ET.4 MSA is a neurodegenerative disorder with α-synuclein pathology with a mixed clinical presentation combining autonomic dysfunction, parkinsonism, and cerebellar or pyramidal symptoms. The initial clinical signs of MSA with prominent parkinsonism can make it difficult to differentially diagnose it from early PD. In addition, up to 30% of patients with MSA with prominent parkinsonism may have a transient response to levodopa therapy.5 ### Methods. Genotyping of the MAPT H1 discriminating SNP (rs1052553) and H1c subhaplotype SNP (rs242557) was performed on a Sequenom MassArray iPLEX platform (San Diego, CA) (primer sequences are available on request) and analyzed with Typer 4.0 software. The rate of genotype calls was ≥95% in each population. The series contained 356 patients with clinical ET, 61 patients with pathologically confirmed MSA, and 409 US control subjects; all samples are North American Caucasians. Numerical variables were summarized with the sample mean, SD, and range (table e-1 on the …

Primary progressive versus relapsing-onset multiple sclerosis: presence and prognostic value of cerebrospinal fluid oligoclonal IgM

Background: There is increasing evidence on cerebrospinal fluid (CSF) oligoclonal IgM (OCIgM) predicting a more aggressive disease course in relapsing–remitting Multiple Sclerosis (MS), while there is a scarcity of data for primary progressive MS (PPMS). Objective: Our aim was to investigate the presence and possible prognostic value of CSF OCIgM in a group of PPMS and in a group of relapsing-onset MS patients. The possible prognostic role of other clinical and biological factors was also evaluated. Methods: We calculated the impact of single clinical and biological factors, including CSF OCIgM at onset, on the probability of reaching an Expanded Disability Status Scale of 3 and 4 in 45 PPMS and 104 relapsing-onset MS patients. Results: CSF OCIgM were found in only 13% of PPMS patients and did not influence the time taken to reach an Expanded Disability Status Scale of 3 and 4. Conversely, they were present in 46% of relapsing-onset MS patients and increased the risk of reaching an Expanded Disability Status Scale of 4. Clinical factors with a negative prognostic value in PPMS were age at onset <30 years and onset with pyramidal symptoms, while onset with sensory symptoms in relapsing-onset MS predicted a more favourable course. Conclusion: This study confirms that, in relapsing-onset MS patients, the presence of CSF OCIgM at onset predicts a worse disease course. In the cohort of PPMS patients, however, CSF OCIgM were rare, suggesting that heterogeneous pathogenetic mechanisms may be involved in the different MS forms.

Clinical, genetic and magnetic resonance findings in an Italian patient affected by l-2-hydroxyglutaric aciduria

L-2-Hydroxyglutaric aciduria (L-2-HGA) is a neurometabolic disease characterized by the presence of elevated levels of 2-hydroxyglutaric acid in the plasma, cerebrospinal fluid and urine. Clinical features in this inherited condition consist of mental deterioration, ataxia and motor deficits with pyramidal and extrapyramidal symptoms and signs. L-2-HGA is caused by mutations in the L-2-HGDH gene which most probably encodes for a L-2-hydroxyglutarate dehydrogenase, a putative mitochondrial protein converting L-2-hydroxyglutarate to alphaketoglutarate. Here, we report a pathogenic nonsense mutation in the L-2-HGDH gene found for the first time in an Italian patient affected by L-2-HGA, reinforcing the previously described phenotype of this rare metabolic disease and confirming the data indicating that mutations in the L-2-HGDH gene cause L-2-HGA.

MRI Eye-of-the-Tiger Sign in Organophosphate Poisoning

We describe the eye-of-the-tiger sign on magnetic resonance imaging (MRI) of the brain in a 40-year-old man presenting with extra pyramidal symptoms like chorea, flexion neck dystonia, tongue tremors, dysarthria and postural instability as the sequelae of organophosphorus poisoning six months previously. This typical radiological sign has been described in extrapyramidal parkinsonian disorders including cortical-basal ganglionic degeneration, early onset levodopa-responsive parkinsonism and Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy) but hitherto has not been reported in insecticide poisoning. T2-weighted scans showed low signal intensity surrounding a central region of high signal intensity in the anteromedial globus pallidus (gliosis), producing an eye-of-the-tiger appearance with the central hyperintense signal intensity better appreciated in T2W and fluid attenuated inversion recovery (FLAIR) sequences.

Falls in Spinocerebellar Ataxias: Results of the EuroSCA Fall Study

To investigate the frequency, details, and consequences of falls in patients with autosomal dominant spinocerebellar ataxias (SCAs) and to derive specific disease-related risk factors that are associated with an increased fall frequency. Two hundred twenty-eight patients with SCA1, SCA2, SCA3, or SCA6, recruited from the EuroSCA natural history study, completed a fall questionnaire that assessed the frequency, consequences, and several details of falls in the previous 12 months. Relevant disease characteristics were retrieved from the EuroSCA registry. The database of the natural history study provided the ataxia severity scores as well as the number and nature of non-ataxia symptoms. Patients (73.6%) reported at least one fall in the preceding 12 months. There was a high rate of fall-related injuries (74%). Factors that were associated with a higher fall frequency included: disease duration, severity of ataxia, the presence of pyramidal symptoms, the total number of non-ataxia symptoms, and the genotype SCA3. Factors associated with a lower fall frequency were: the presence of extrapyramidal symptoms (more specifically dystonia of the lower limbs) and the genotype SCA2. The total number of non-ataxia symptoms and longer disease duration were independently associated with a higher fall frequency in a logistic regression analysis, while the presence of extrapyramidal symptoms was independently associated with a lower fall frequency. Our findings indicate that, in addition to more obvious factors that are associated with frequent falls, such as disease duration and ataxia severity, non-ataxia manifestations in SCA play a major role in the fall etiology of these patients.

Amisulpride versus other atypical antipsychotics for schizophrenia.

In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of amisulpride differs from that of other second generation antipsychotics. To evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO. We included randomised, at least single-blind, trials comparing oral amisulpride with oral forms of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. We extracted data independently. For continuous data we calculated weighted mean differences (MD), for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. The review currently includes ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50). Amisulpride induced less weight gain than risperidone (n=585, 3 RCTs, MD -0.99 CI -1.61 to -0.37) or olanzapine (n=671, 3 RCTs, MD -2.11 CI -2.94 to -1.29). Olanzapine was also associated with a higher increase of glucose (n=406, 2 RCTs, MD -7.30 CI -7.62 to -6.99). There was no difference in terms of cardiac effects and extra pyramidal symptoms (EPS) compared with olanzapine (akathisia: n= 587, 2 RCTs, RR 0.66 CI 0.36 to 1.21), compared with risperidone (akathisia: n=586, 3 RCTs, RR 0.80 CI 0.58 to 1.11) and compared with ziprasidone (akathisia: n=123, 1 RCT, RR 0.63, CI 0.11 to 3.67). There is little randomised evidence comparing amisulpride with other second generation antipsychotic drugs. We could only find trials comparing amisulpride with olanzapine, risperidone and ziprasidone. We found amisulpride may be somewhat more effective than ziprasidone, and more tolerable in terms of weight gain and other associated problems than olanzapine and risperidone. These data, however, are based on only ten short to medium term studies and therefore too limited to allow for firm conclusions.

Cortical Abnormalities in Creutzfeldt-Jakob Disease Measured by MEG, a Case Report

Event Abstract Back to Event Cortical Abnormalities in Creutzfeldt-Jakob Disease Measured by MEG, a Case Report Eero Pekkonen1*, Juha Wilenius2, Jukka Lyytinen1, Anders Paetau3, Maarit Palomäki4 and Jyrki Mäkelä5 1 University of Helsinki, Department of Neurology, Finland 2 University of Helsinki, BioMag laboratory, Finland 3 University of Helsinki, Department of Pathology, Finland 4 University of Helsinki, Department of Radiology, Finland 5 Helsinki University Central Hospital, BioMag laboratory, Finland Creutzfeldt-Jakob Disease (CJD) is a rare neurodegenerative disease, which belongs to a group of spongiform encephalopathies termed prion diseases.Main symptoms of CJD are progressive dementia, py-ramidal and extrapyramidal symptoms, and myoclonus. Currently there is no effective therapy for CJD. Definite diagnosis is based on autopsy findings.Here we report a male patient with a rapidly progres-sive memory disorder, ataxia and myoclonus. EEG showed slow wave activity, and head MRI revealed in-creased basal ganglia and left-dominant increase in cor-tical signal intensity. In cerebrospinal fluid (CSF) 14-3-3 test was positive. The autopsy confirmed the sporadic CJD.A 306-channel MEG measurement was performed to the patient. Spontaneous brain activity and auditory evoked fields (AEF) were recorded.Both hemispheres had slow wave activity and periodic sharp waves, activity being more pronounced in the left, more damaged, hemisphere. The source of auditory N100m were more lateral in the left than in the right hemisphere. P200m was larger and more posterior in the left hemisphere compared with the right hemisphere. This is the first MEG-recording of a patient with spo-radic CJD. The more damaged left hemisphere in MRI had more pronounced slow and sharp waves in MEG. The sources of auditory responses and amplitude of later 200m deflection were different between the more and less damaged hemispheres. MEG appears to be suitable to investigate and locate brain activity in prion diseases. Conference: Biomag 2010 - 17th International Conference on Biomagnetism , Dubrovnik, Croatia, 28 Mar - 1 Apr, 2010. Presentation Type: Poster Presentation Topic: MEG: Clinical applications Citation: Pekkonen E, Wilenius J, Lyytinen J, Paetau A, Palomäki M and Mäkelä J (2010). Cortical Abnormalities in Creutzfeldt-Jakob Disease Measured by MEG, a Case Report. Front. Neurosci. Conference Abstract: Biomag 2010 - 17th International Conference on Biomagnetism . doi: 10.3389/conf.fnins.2010.06.00286 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 05 Apr 2010; Published Online: 05 Apr 2010. * Correspondence: Eero Pekkonen, University of Helsinki, Department of Neurology, Helsinki, Finland, eero_pekkonen@hotmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Eero Pekkonen Juha Wilenius Jukka Lyytinen Anders Paetau Maarit Palomäki Jyrki Mäkelä Google Eero Pekkonen Juha Wilenius Jukka Lyytinen Anders Paetau Maarit Palomäki Jyrki Mäkelä Google Scholar Eero Pekkonen Juha Wilenius Jukka Lyytinen Anders Paetau Maarit Palomäki Jyrki Mäkelä PubMed Eero Pekkonen Juha Wilenius Jukka Lyytinen Anders Paetau Maarit Palomäki Jyrki Mäkelä Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

P03-113 - Treatment of extrapyramidal symptoms due to neuroleptic drugs use

IntroductionThe extra pyramidal effects related to the use of neuroleptics are a limiting factor in schizophrenia treatment.ObjectiveThe aim of this study was to identify the neuroleptics prescribed for schizophrenic patients in a public health service, the extra pyramidal symptoms (EPS) incidence and its treatment.MethodsOur restrospective study included 40 patients with mean age of 39.13 ± 2.19 in a treatment period of of 134.17 ± 16.83 days. The data were randomly collected from medical records of these patients.ResultsThe patients under study received typical neuroleptics (31.03%),atypical agents (37.93%) or association of both (31.03%). EPS was observed in 65.52% patients of which, 44.83% even though receiving biperiden 2mg, still have EPS. 20.69% were not receiving anticolinergic drug treatment for EPS, but promethazine or anticonvulsants. From the 34.48% who did not showed EPS, 20.69% had biperiden prescription and 13.79 % had been treated with olanzapine, clozapine or risperidone associated or not to clonazepam 2mg. Weigth gain of 5.20 ± 1.14 kg was observed in our total sample.ConclusionsWe suggest the use of EPS evaluation scale (Sympson - Angus or Barnes). 65.52 % of the patients under study had EPS and 20.69% of them had no prescription of central acting anticholinergic drug. 44.83% even though receiving biperiden 2mg, still have EPS.

Preparation and comparative evaluation of sustained release metoclopramide hydrochloride matrix tablets

Metoclopramide hydrochloride (MCP) is commonly used for the management of gastrointestinal disorders. Frequent administration and the undesired side effects (extra pyramidal symptoms) of the drug on the central nervous system due to the fluctuations of its plasma concentrations may lead to patient incompliance, and hence, improper therapy. Therefore, the present work will be devoted to formulate the drug in sustained release formulations. MCP was incorporated in 12 formulae containing different polymers and/or different polymer ratios. These polymers were hydroxypropylmethyl cellulose (HPMC), carboxymethylcellulose (CMC) and ethyl cellulose (EC). Sodium starch glycolate (SSG) was added to some formulae in different amounts in order to soften and/or disintegrate the tablets. Both direct compression and granulation techniques were used to prepare the tablets. The physical properties were found to be satisfactory for all the formulae. The dissolution profiles of the tablets were constructed using the change-over method. The drug release involved a combination of both diffusion and polymer-chain relaxation mechanisms. The time required to release 50% of MCP ranged from 1.2 to more than 8h. Direct compression and dry granulation techniques produced sufficient sustaining of the drug release. However, the pellets made by wet granulation released MCP in about 2h, i.e., pelletization spheronization technique was not effective in sustaining the drug.

Progressive supranuclear palsy--20 years later.

Reviewing the literature since recognition of progressive supranuclear palsy (PSP) as a clinicopathological entity 20 years ago, the present state of knowledge is delineated. The etiology of PSP is still unknown. The clinical hallmarks are supranuclear palsy of vertical gaze, axial dystonia in extension and pseudobulbar palsy with marked dysarthria and dysphagia. Accessory features include subcortical dementia, mental, extrapyramidal, pyramidal and cerebellar symptoms. PSP is a disease of the presenium (average age at onset, 59.6 years) with a male preponderance (60% men). The onset is insidious with vague complaints of dysequilibrium (60%), mental changes (46%) and disturbed vision (21%), often preceding abnormal neurological findings. The important borderland and main differential diagnosis is parkinsonism. However, in PSP, responsiveness to antiparkinsonian agents is poor and progression is rapid and fatal within few years (average survival time, 5.7 years). Promising diagnostic tools at present include CT-scanning and neuro-otologic and -ophthalmologic examination. Neuropathological findings, confined to specific diencephalic, brainstem and cerebellar nuclei, include neurofibrillary tangles (ultrastructurally different from those seen in other CNS disorders), neuron loss and gliosis. The importance of research on neurocytochemistry, brain ultrastructure and immunology in the current investigation of PSP is outlined.

Decreased sympathetic outflow to muscles in patients with cervical spondylosis.

To clarify the pathogenesis of neurologic symptoms of a vascular nature that may accompany cervical spondylosis (CS), we measured the sympathetic outflow to muscles (muscle sympathetic nerve activity: MSNA) in 8 ambulatory patients with CS and 10 healthy volunteers (controls). The burst rate and incidence of MSNA at rest were significantly lower in patients with CS than in controls (P < 0.01). There were no differences between the 2 groups in either resting heart rate or blood pressure. During a head-up tilting, the changes in MSNA were slightly greater in CS patients than controls due to reduced baseline levels of MSNA in CS patients. The burst incidence of MSNA in CS was significantly negatively correlated with the severity of pyramidal tract symptoms (P < 0.05). The decreased MSNA at rest in CS patients may be due to a spinal cord compression resulting from posterior spondylotic changes in the cervical spine.

Impact of schizophrenia and schizophrenia treatment-related adverse events on quality of life: direct utility elicitation

ObjectiveTo examine the impact of schizophrenia, its treatment and treatment-related adverse events related to antipsychotics, on quality of life from the perspective of schizophrenia patients and laypersons.MethodsHealth state descriptions for stable schizophrenia, extra pyramidal symptoms (EPS), hyperprolactinemia, diabetes, weight gain and relapse were developed based on a review of the literature and expert opinion. The quality of life impact of each health state was elicited using a time trade-off instrument administered by interview to 49 stable schizophrenia patients and 75 laypersons. Regression techniques were employed to examine the importance of subject characteristics on health-related utility scores.ResultsPatients and laypersons completed the interview in similar times. Stable schizophrenia had the highest mean utility (0.87 and 0.92 for laypersons and patients respectively), while relapse (0.48 and 0.60) had the lowest mean utility. Of the treatment-related adverse events, EPS had the lowest mean utility (0.57 and 0.72, respectively). Age, gender and PANSS score did not influence the utility results independently of health state. On average, patient utilities are 0.077 points higher than utilities derived from laypersons, although the ranking was similar between the two groups.ConclusionEvents associated with schizophrenia and treatment of schizophrenia can bring about a significant detriment in patient quality of life, with relapse having the largest negative impact. Results indicate that patients with stable schizophrenia are less willing to trade years of life to avoid schizophrenia-related symptoms compared to laypersons. Both sets of respondents showed equal ability to complete the questionnaire.

A multifactorial prognostic index in multiple sclerosis

The ability to predict the future progression of MS represents a key issue for the neurologist. The aim of the study was to create a multifactorial prognostic index (MPI) providing the probability of a severe MS course at diagnosis based on clinical and immunological CSF parameters. 64 clinically definite relapsing-remitting (RR)MS patients (38 benign, 26 severe MS) followed up for at least 10 years were included. Clinical and demographic details, EDSS after 5 and 10 years, progression index, relapse number and rate, time to a second relapse were assessed. CSF and serum samples collected at diagnosis were examined for CSF IgM and IgG oligoclonal bands (OB) and quantitative IgM and IgG determination. Kaplan-Meier analysis showed that the probability of reaching an EDSS score of 3 or 4 was significantly influenced by the presence of IgMOB (p<0.01 and p<0.01, log-rank test) and by the symptoms at onset (p=0.04 and p=0.03, log-rank test). These results were confirmed at multivariate analysis (Cox model). Univariate logistic analysis showed that IgMOB presence predicted a severe MS course (OR=9.33, CI=2.92- 29.88), whereas sensory symptoms at onset predicted a benign MS course (OR=0.12, CI=0.02-0.56). Using multivariate logistic regression the factors found to be significant were: presence/absence of IgMOB (p<0.01), onset with sensory (p<0.01) and pyramidal symptoms (p=0.01), and first inter-attack interval (p=0.03). The individual probability of a severe evolution was thus estimated by a simple formula comprising clinical and biological markers of prognosis available at diagnosis (pyramidal and sensory symptoms, months to the 2nd episode, and IgMOB presence/absence), giving the probability of developing a severe MS course. Applied to the same patient cohort this formula showed a global error of 6/64 (9.37%). We then used another independent series of 65 RRMS patients to validate this model. In this second patient cohort, 4/45 BMS and 4/20 SMS patients were found to have been incorrectly classified (based on the formula), with a global error of 8/65 (12.31%). For the first time we created a MPI, using clinical and biological markers to predict the clinical course of MS at diagnosis. This index can support the clinician in patient counselling, therapeutic choices, as well as in patient selection criteria for clinical trials.