Basal ganglia calcifications: No association with cognitive function.

BACKGROUND AND PURPOSE: Basal ganglia calcifications (BGC), a form of vascular calcification, are a common brain computed tomography (CT) finding. We investigated whether BGC are associated with cognitive function and examined the association between vascular risk factors and BGC. MATERIAL AND METHODS: Patients who visited a memory clinic of a Dutch general hospital between April 2009 and April 2015 were included. The patients underwent a standard diagnostic work up including cognitive tests (Cambridge Cognitive Examination, including the Mini Mental State Examination) and brain CT. Vascular risk factors such as hypertension, diabetes mellitus, hyperlipidemia and smoking were assessed. CTs were analyzed for presence and severity (absent, mild, moderate or severe) of BGC. Multivariable logistic regression was used to identify risk factors for BGC and linear regression for the association between BGC and cognitive function. RESULTS: Of the 1992 patients, 40.3% was male. The median age was 80 years and 866 patients (43.5%) had BGC. BGC was associated with female gender (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06-1.53, p 0.011), and inversely associated with hypertension (OR 0.74, 95% CI 0.60-0.89, p 0.002) and use of antihypertensive drugs (OR 0.79, 95% CI 0.64-0.98, p 0.031). No association was found between presence and severity of BGC and cognitive function or other vascular risk factors. CONCLUSIONS: No association with cognitive function was found. Risk factors for BGC were female gender, while hypertension and antihypertensive drug use were associated with a lower risk of BGC.

The factor structure of extrapyramidal symptoms evaluated using the Drug-Induced Extrapyramidal Symptoms Scale in patients with schizophrenia: Results from the 2016 REAP AP-4 study.

INTRODUCTION: Drug-induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychiatry. This study aimed to examine the factor structure of drug-induced extrapyramidal symptoms observed in patients with schizophrenia and assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). METHODS: The participants were 1478 patients with a diagnosis of schizophrenia whose EPS was assessed using the DIEPSS in India, Indonesia, Japan, Malaysia, and Taiwan in the 2016 REAP AP-4 study. The records of the participants were randomly divided into two subgroups: the first for exploratory factor analysis of the eight DIEPSS items, and the second for confirmatory factor analysis. RESULTS: The factor analysis identified three factors: F1 (gait and bradykinesia), F2 (muscle rigidity and tremor), and F3 (sialorrhea, akathisia, dystonia, and dyskinesia). CONCLUSION: The results suggest that the eight individual items of the DIEPSS could be composed of three different mechanisms: acute parkinsonism observed during action (F1), acute parkinsonism observed at rest (F2), and central dopaminergic mechanisms with pathophysiology other than acute parkinsonism (F3).

Prevalence and Association of Basal Ganglia Calcifications and Depressive Symptoms in Patients With Mild Cognitive Impairment or Dementia.

AIM: The aim of this study is to investigate the association between basal ganglia calcification (BGC) and depressive symptoms within older adults with mild cognitive impairment (MCI) or dementia. METHODS: For this cross-sectional study, we included patients with MCI or dementia who visited the memory clinic between April 2009 and April 2015. All patients underwent a standard diagnostic workup, including assessment of depressive symptoms with the Geriatric Depression Scale and computed tomography imaging of the brain. Computed tomography scans were assessed for presence and severity of BGC. To analyse the association between BGC and depressive symptoms, binary logistic regression models were performed with adjustment for age, sex, cardiovascular risk factors, and cardiovascular diseases. RESULTS: In total, 1054 patients were included (median age: 81.0 y; 39% male). BGC was present in 44% of the patients, of which 20% was classified as mild, 20% as moderate, and 4% as severe. There were 223 patients (21%) who had a Geriatric Depression Scale score indicative of depressive symptoms. No association was found between the presence or severity of BGC and depressive symptoms. CONCLUSIONS: Although both BGC and depressive symptoms were common in patients with MCI or dementia, no association was demonstrated between the presence or severity of BGC and depressive symptoms.

Comparison of Extrapyramidal Symptoms Among Outpatients With Schizophrenia on Long-Acting Injectable Antipsychotics.

BACKGROUND: Extrapyramidal symptoms (EPSs) are adverse effects of antipsychotics. Different risks of EPSs have been attributed to the 3 classes of antipsychotics. This study aimed to assess EPS in a clinical sample of schizophrenia patients who are on LAI and compare the severity of EPSs among the following 3 antipsychotic groups: (1) partial agonist, (2) second-generation antipsychotics, and (3) first-generation antipsychotics. METHODS: Ninety-two patients were recruited from the Schizophrenia Program Injection Clinic. Using the Extrapyramidal Symptom Rating Scale (ESRS), severity of EPS was assessed and information regarding factors associated with risk of EPS, including coprescriptions, comorbidities, and demographics, was obtained from medical charts. Group differences in ESRS scores and subscores were analyzed using 1-way analyses of variances. RESULTS: Among the 3 groups, there was no significant difference in total ESRS scores and subscores. Risperidone was associated with higher ESRS scores when compared with paliperidone, aripiprazole, and flupenthixol. Doses above maximum were commonly used in the paliperidone group, and there was no significant difference in total ESRS scores between the low, average, or above-maximum doses of paliperidone. CONCLUSIONS: Our results demonstrated a comparative risk of EPS across all 3 antipsychotic classes. Risperidone was associated with more EPS compared with other medications. A higher threshold for the "maximum dose" of paliperidone could be considered and higher doses used with the same cautions as low-average doses.

Movement Disorders and Mortality in Severely Mentally Ill Patients: The Curacao Extrapyramidal Syndromes Study XIV.

BACKGROUND AND HYPOTHESIS: There is a substantial gap in life expectancy between patients with severe mental illness (SMI) and the general population and it is important to understand which factors contribute to this difference. Research suggests an association between tardive dyskinesia (TD) and mortality; however, results are inconclusive. In addition, studies investigating associations between parkinsonism or akathisia and mortality are rare. We hypothesized that TD would be a risk factor for mortality in patients with SMI. STUDY DESIGN: We studied a cohort of 157 patients diagnosed predominantly with schizophrenia on the former Netherlands Antilles. TD, parkinsonism, and akathisia were assessed with rating scales on eight occasions over a period of 18 years. Twenty-four years after baseline, survival status and if applicable date of death were determined. Associations between movement disorders and survival were analyzed using Cox regression. Sex, age, antipsychotics, antidepressants and benzodiazepines at each measurement occasion were tested as covariates. STUDY RESULTS: Parkinsonism was a significant risk factor with an HR of 1.02 per point on the motor subscale of the Unified Parkinson's Disease Rating Scale (range 0-56). TD and akathisia were not significantly associated with mortality. CONCLUSIONS: Parkinsonism may be an important risk factor for mortality in SMI patients. This finding calls for more follow-up and intervention studies to confirm this finding and to explore whether treatment or prevention of parkinsonism can reduce excess mortality.

Basal Ganglia Calcification Is Associated With Local and Systemic Metabolic Mechanisms in Adult Hypoparathyroidism.

CONTEXT: Hypoparathyroidism is characterized by low serum calcium, increased serum phosphorus, and inappropriately low or decreased serum parathyroid hormone, which may be associated with soft tissue calcification in the basal ganglia of the brain. OBJECTIVE: To assess the prevalence and factors involved in the pathophysiology of basal ganglia calcification (BGC) in the brain in chronic hypoparathyroidism and to evaluate proposed pathophysiologic mechanisms. DESIGN: Case-control study with retrospective review of medical records over 20 years. SETTING: Single academic medical center. PATIENTS: 142 patients with chronic hypoparathyroidism and computed tomography (CT) head scans followed between January 1, 2000 and July 9, 2020, and 426 age- and sex-matched controls with CT head scans over the same interval. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Demographic, biochemical, and CT head imaging findings, with semiquantitative assessment of volumetric BGC. RESULTS: The study found that 25.4% of 142 patients followed for a median of 17 years after diagnosis of chronic hypoparathyroidism had BGC, which developed at a younger age than in controls. BGC was 5.1-fold more common in nonsurgical patients and less common in postsurgical patients. Low serum calcium and low calcium/phosphate ratio correlated with BGC. Neither serum phosphorus nor calcium × phosphate product predicted BGC. Lower serum calcium was associated with greater volume of BGC. The extent of BGC varied widely, with nonsurgical patients generally having a greater volume and distribution of calcification. CONCLUSIONS: BGC is associated with low serum calcium and low serum calcium/phosphate ratio, which may be related to severity of the disease, its etiology, or duration of treatment.

Prevalence of antipsychotic-induced extrapyramidal symptoms and their association with neurocognition and social cognition in outpatients with schizophrenia in the "real-life".

First generation antipsychotics (FGAs) are more likely to induce extrapyramidal side-effects (EPS) than second generation antipsychotics (SGAs), and EPS have been shown associated to cognitive deficits in schizophrenia. So far, no study has explored the relationships between EPS and social cognition (SC) in people with schizophrenia. Therefore, we assessed the prevalence of EPS in a large sample of drug-treated community-dwelling persons with schizophrenia and explored their relationships with patients' neurocognitive and SC abilities. 875 patients underwent EPS, psychopathological, neurocognitive and SC assessments by means of standardized measures. Relationships between EPS, psychopathology and neurocognitive and SC measures were investigated by correlation tests. Moreover, a partial correlation network was computed by means of a network analysis. 256 patients were treated with FGAs alone or in combination with SGA and 619 with SGAs. EPS were significantly more frequent in FGA-treated group than in the SGA-treated one. Patients with EPS disclosed a more severe psychopathology and were more impaired in neurocognitive and SC measures compared to those without EPS. Disorganization, expressive deficit, and duration of illness were significantly associated to both neurocognitive and SC measures while EPS were associated to neurocognitive measures only. The network analysis showed that parkinsonism was the sole EPS directly connected to both psychopathological and neurocognitive indices whereas no direct connection emerged between EPS and SC measures. Present findings confirm that EPS are still present in the era of SGAs and contribute, together with other clinical variables, to the neurocognitive but not to the SC impairment of patients with schizophrenia.

Basal ganglia calcification in hypoparathyroidism and pseudohypoparathyroidism: local and systemic metabolic mechanisms.

BACKGROUND: Hypoparathyroidism and pseudohypoparathyroidism are rare disorders of mineral metabolism which may be associated with soft tissue calcification in the basal ganglia in the brain, and occasionally the skin and other tissues. The basal ganglia are the most common sites of calcification in the central nervous system in these disorders, and were first associated with this manifestation in a report from the Mayo Clinic in 1939. The reasons why the basal ganglia are a common site of soft tissue calcification in these rare disorders has been a matter of investigation for many years. FINDINGS: Due to recent increased understanding of phosphate transport and new insights gained from mRNA expression in the basal ganglia, the pathophysiology of basal ganglia calcification (BGC) is now clearer. There is evidence that the absence of parathyroid hormone in hypoparathyroidism may play a direct role, but this is clearly not the case in pseudohypoparathyroidism, which is associated with increased parathyroid hormone levels. Maintaining the calcium/phosphorus ratio as close to normal as possible, and maintaining normal serum phosphate levels, may help mitigate the progression of BGC. There is no evidence of regression of BGC with conventional treatment, and long-term data with adjunctive or replacement therapy with parathyroid hormone or its analogues are not yet available. PURPOSE OF THE REVIEW: This review will focus on the pathophysiology of BGC in hypoparathyroidism and pseudohypoparathyroidism, and review the proposed pathophysiologic mechanisms, as well as the clinical implications of BGC on patient quality of life.

Spontaneous and emergent extrapyramidal syndromes in Black Africans with first-episode schizophrenia and first exposure to antipsychotics.

BACKGROUND: Persons of African ancestry are thought to carry a higher risk for extrapyramidal syndromes (EPS) in schizophrenia. AIM: We investigated the phenomenon of spontaneous and treatment-emergent EPS in a sample comprising Xhosa (South Africa) and Yoruba (Nigeria) Africans with first-episode schizophrenia and first exposure to antipsychotics. METHODS: The Extrapyramidal Symptom Rating Scale (ESRS) and a variety of validated tools were used for the assessment of participants before, and two-weekly after treatment with low dose flupenthixol decanoate. Participants were followed up for 12 months. Association of EPS with clinical characteristics was investigated using Pearson's correlation and linear regression analyses. RESULTS: Of 88 participants at baseline, 16 (18.1%) had at least one definite EPS prior to antipsychotic exposure and 34 (38.6%) had treatment-emergent EPS. While spontaneous Parkinsonism was associated with negative symptoms (r = 0.2, p = 0.043; ß = 0.6, p = 0.043), treatment-emergent EPS demonstrated non-significant correlations with clinical characteristics. Apart from dyskinesia, the frequency of treatment-emergent EPS decreased over 12 months observation. CONCLUSION: These findings support the hypothesis suggesting that spontaneously occurring Parkinsonism in schizophrenia may be the motor spectrum of negative symptomatology. Future studies of this relationship may lead to early identification of patients who may be more sensitive to EPS.

[Basal ganglia calcification]. / Calcifications des noyaux gris centraux.

Calcifications of the basal ganglia are frequently seen on the cerebral CT scans and particularly in the globus pallidus. Their frequency increases physiologically with age after 50 years old. However, pathological processes can also be associated with calcium deposits in the gray nuclei, posterior fossa or white matter. Unilateral calcification is often related to an acquired origin whereas bilateral ones are mostly linked to an acquired or genetic origin that will be sought after eliminating a perturbation of phosphocalcic metabolism. In pathological contexts, these calcifications may be accompanied by neurological symptoms related to the underlying disease: Parkinson's syndrome, psychiatric and cognitive disorders, epilepsy or headache. The purpose of this article is to provide a diagnostic aid, in addition to clinical and biology, through the analysis of calcification topography and the study of different MRI sequences.

Basal ganglia infarction after mild head trauma in pediatric patients with basal ganglia calcification.

OBJECTIVES: Incidence rate of basal ganglia infarction (BGI) after mild head trauma was reported higher in children with basal ganglia calcification (BGC). We would like to review patients with BGC showed in head CT scan to see the incidence rate of stroke in these patients and the correlation of variables in these cases. PATIENTS AND METHODS: CT imaging data of cases with diagnosis of mild traumatic brain injury (mTBI) in a large tertiary pediatric center between Mar. 2014 and Mar. 2019 was retrospectively reviewed. Cases with findings of punctate calcification in the region of basal ganglion in CT scan were included. Correlation of variables of these cases (age, side and volume of basal ganglion calcification) with the diagnosis of BGI was the focus of this study. RESULTS: 37 patients (26 males, 9 females, median age: 3.88±3.54) were included in this study. 17 cases (45.9 %) were diagnosed of BGI and were admitted into the department of neurosurgery. Altogether 63 sides of BGC were categorized into two groups based on whether BGI happened and ROC curve was drawn. ROC curve showed when the cut-off point was 6.55 mm3, the sensitivity was 88.9 % and the specificity was 87.5 %; the area under curve was 0.849 (p<0.01). All the cases were divided into two groups according to whether basal ganglia infarction occurred or not. Mann-Whitney U test showed significant difference between these two groups in age (p=0.01). ROC curve of how age affect BGI after mTBI were drawn. The cut-off point was 3.25 years, and the sensitivity was 65.0 % and the specificity was 88.2 %; the area under curve was 0.746 (p=0.01). All patients received conservative treatment and recovered. CONCLUSION: Incidence rate is higher in children with BGC after mild head injury than that of other children. Larger BGC volume indicates higher risk of developing infarction after minor head injury. Older children with BGC are less-likely getting BGI after mTBI.

Extrapyramidal reactions following treatment with antidepressants: Results of the AMSP multinational drug surveillance programme.

Objectives: Extrapyramidal symptoms (EPS) are a common adverse effect of antipsychotics. However, there are case reports describing EPS following treatment with antidepressants. It is not fully understood how antidepressants cause EPS, but a serotonergic input to dopaminergic pathways is a probable mechanism of action.Methods: Data from a multicenter drug-surveillance programme (AMSP, 'drug safety in psychiatry') which systemically documents severe drug reactions during psychiatric inpatient admissions, were reviewed to assess for EPS associated with antidepressant treatment. We identified 15 such cases, which were studied to detect similarities and to characterise risk factors.Results: We report on 15 patients with EPS following antidepressant-therapy between 1994 and 2016. EPS frequently occurred with selective serotonin reuptake inhibitor (SSRI) treatment alone (7/15 cases) or concomitant SSRI treatment (6/15 cases). EPS were most frequent with escitalopram-treatment (5 cases). The most common EPS was atypical dyskinesia (6/15 cases) followed by akathisia (4/15 cases). The mean age of onset for EPS was 54.93 years (SD 17.9). EPS occurred at any dosage and equally often in men and women.Conclusions: Our results highlight the possibility of EPS as an important, although uncommon, adverse effect of antidepressants. Clinicians should beware of this adverse effect and monitor early warning signs carefully.

Incidence and Trends of Progressive Supranuclear Palsy and Corticobasal Syndrome: A Population-Based Study.

BACKGROUND: Few studies have investigated the incidence of PSP and CBS in the population. OBJECTIVE: To examine the incidence of and trends in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) in a population-based cohort of residents of Olmsted County, MN. METHODS: We used the 1991-2005 population-based, Olmsted County Parkinsonism-cohort study, defined via the Rochester Epidemiology Project. A movement-disorder specialist reviewed medical records, to confirm PSP and CBS diagnoses. RESULTS: We identified 21 patients with these diagnoses 1991-2005 : 18 (85.7%), PSP; 3 (14.3%), CBS. The median diagnosis age was 78 (range: 66-88). 13/21 (62.0%) were male. MRI was performed pre-diagnosis in 11 patients (8 PSP and 3 CBD); 10 showed atrophy consistent with clinical diagnoses. We observed concordance between clinical and pathological diagnoses in two PSP patients who underwent autopsy. Combined incidence for PSP and CBS in Olmsted County was 3.1 per 100,000 person-years (2.6 per 100,000 person-years, PSP; 0.4 per 100,000 person-years, CBS). Incidence was higher in men (4.5, 95% CI, 2.0-7.0) than women (1.8, 95% CI, 0.5-2.9). A combined, significant trend of increasing incidence was observed between 1991 and 2005 (B=0.69, 95% CI 0.42, 0.96, p<0.001). Median time from symptom onset to death among both groups was 6 years (range PSP, 1-10 years; range CBS, 3-8 years). CONCLUSIONS: The combined incidence for PSP and CBS was 3.1 per 100,000 person-years, higher in men than women. We observed a significant increase in both PSP and CBS, likely due to advancing imaging technology and improved diagnostic ability among physicians.

Targeted SLC19A3 gene sequencing of 3000 Saudi newborn: a pilot study toward newborn screening.

BACKGROUND: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is an autosomal recessive neurometabolic disorder mostly presented in children. The disorder is described as having subacute encephalopathy with confusion, dystonia, and dysarthria triggered by febrile illness that leads to neuroregression and death if untreated. Using biotin and thiamine at an early stage of the disease can lead to significant improvement. METHODS: BTBGD is a treatable disease if diagnosed at an early age and has been frequently reported in Saudi population. Keeping this in mind, the current study screened 3000 Saudi newborns for the SLC19A3 gene mutations using target sequencing, aiming to determine the carrier frequency in Saudi Population and whether BTBGD is a good candidate to be included in the newborn-screened disorders. RESULTS: Using targeted gene sequencing, DNA from 3000 newborns Saudi was screened for the SLC19A3 gene mutations using standard methods. Screening of the SLC19A3 gene revealed a previously reported heterozygous missense mutation (c.1264A>G (p.Thr422Ala) in six unrelated newborns. No probands having homozygous pathogenic mutations were found in the studied cohort. The variant has been frequently reported previously in homozygous state in Saudi population, making it a hot spot mutation. The current study showed that the carrier frequency of SLC19A3 gene mutation is 1 of 500 in Saudi newborns. CONCLUSION: For the first time in the literature, we determined the carrier frequency of SLC19A3 gene mutation in Saudi population. The estimated prevalence is too rare in Saudi population (at least one in million); therefore, the data are not in favor of including such very rare disorders in newborn screening program at population level. However, a larger cohort is needed for a more accurate estimate.

Drug-Induced Extrapyramidal Symptoms Scale of the Norwegian version: inter-rater and test-retest reliability.

Background: The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) is a multidimensional rating scale designed for the fast, easy and reliable assessment of extrapyramidal symptoms (EPSs) induced by antipsychotics. Aim: The aim of this study was to validate the level of inter-rater and test-retest reliability of the Norwegian translation of this scale. Methods: A total of 125 video clips showing a variety of or no signs of EPSs were used in the present study. The participants recorded were Japanese psychiatric patients receiving first- and/or second-generation antipsychotics. A total of 103 patients (47 males and 56 females), diagnosed with schizophrenia (n = 68) or mood disorders (n = 35) appeared in the video clips. Their mean age was 48.7 ± 16.3 years (range 18-80) at the time of video recording. Inter-rater agreement was assessed with five raters and test-retest reliability with three. Results: Inter-rater reliability analyses showed interclass correlation coefficients (ICCs) ranging from 0.74 to 0.93 for each individual item. Test-retest reliability analysed independently for each rater ranged from 0.71 to 0.96. Conclusions: Inter-rater and test-retest agreement exhibited satisfactory ICC levels above 0.70. The Norwegian version of the DIEPSS is a reliable instrument for the assessment of drug-induced EPSs.

Psychopathology and extrapyramidal side effects in smoking and non-smoking patients with schizophrenia: Systematic review and meta-analysis of comparative studies.

The association between smoking and psychopathology and extrapyramidal side effects (EPSE) in schizophrenia has been controversial. This systematic review and meta-analysis compared psychopathology and EPSE between smoking and non-smoking schizophrenia patients. The PubMed, EMBASE, PsycINFO, Cochrane Library, and Web of Science databases were independently and systematically searched by two researchers to identify relevant articles. Standardized mean differences (SMDs) and their 95% confidence intervals (CI) were calculated with random effect models. Subgroup and meta-regression analyses were performed to explore sources of heterogeneity. The systematic review and meta-analysis included 29 studies that compared psychotic, depressive and anxiety symptoms and EPSE between smoking (n = 3591) and non-smoking schizophrenia patients (n = 2980). Smoking patients had significantly more severe positive symptoms (24 studies; SMD = 0.33, 95% CI: 0.16 to 0.50, P < 0.001), but less severe EPSE (7 studies; SMD = -0.20, 95% CI: -0.38 to -0.02, P = 0. 03). No significant group differences in negative, depressive and anxiety symptoms were found. In conclusion, this systematic review and meta-analysis found that smoking schizophrenia patients had more severe positive symptoms but less severe EPSE than non-smoking patients.

Physical health status of older adults with severe mental illness: The PHiSMI-E cohort study.

The objective was to use various somatic parameters as basis for investigating the physical health of older adults with severe mental illnesses (SMI). A cross-sectional study design is performed by using baseline data from the Physical Health in SMI-elderly (PHiSMI-E) study. Data were collected using the Nursing Monitoring of Somatic Status and Lifestyle - Mental Health instrument in adults aged over 60 with SMI in a large Dutch mental health institute. Ninety-nine elderly SMI patients were included. Somatic comorbidity (84.8%), use of somatic medication (77.7%) and polypharmacy (67.7%) were prevalent. Extrapyramidal symptoms were experienced by 51% of patients, mainly in the subgroup with psychotic disorders (75.6%). Unhealthy diet was reported in 16.2%, obesity in 27.3%, and physical inactivity in 57.6%. Fatigue (67.7%) and dry mouth (66.6%) were the commonest reported physical symptoms. Mean VAS score (scale 0-10) indicating participants' self-perceived physical health was 6.7 (SD ± 1.6). After division of the total patient group into tertiles based on the VAS scores, the lowest tertile was characterized by less physical activity, unhealthier diet, more use of medication, more fatigue, somnolence, and inner agitation. In conclusion, impaired physical health status was common in these older patients with SMI. Although they had more psychiatric and somatic comorbidity than adult SMI patients described in the literature, they had a healthier lifestyle. To reduce morbidity and premature mortality in these frail patients, it is essential that healthcare providers are aware of the high prevalence of somatic comorbidity and symptoms, and of their interactions with the psychiatric disorders. This study improves our understanding of differences in vulnerability factors of older patients with SMI. The (early) detection of somatic comorbidities may improve long-term health outcomes of these patients.

Using an Integrated Care Pathway for Late-Life Schizophrenia Improves Monitoring of Adverse Effects of Antipsychotics and Reduces Antipsychotic Polypharmacy.

OBJECTIVE: Antipsychotic use in older patients is associated with many adverse effects, including tardive dyskinesia and extrapyramidal symptoms, which, in turn, increase the risk of falling. Antipsychotics are also associated with metabolic syndrome and cognitive impairment in older patients. Integrated care pathways (ICPs) are designed to manage specific conditions using standardized assessments and measurement-based interventions. This study aims to compare the use of recommended tools to monitor for adverse effects associated with antipsychotics in older patients managed within an ICP and those managed under usual care conditions-i.e., treatment as usual (TAU). METHODS: We reviewed and compared the health records of 100 older patients enrolled in an ICP for late-life schizophrenia with those of 100 older patients treated with antipsychotics under TAU conditions. RESULTS: Monitoring rates were significantly higher in the ICP group than in the TAU group for all assessments: extrapyramidal symptoms (94% versus 5%), metabolic disturbances (91% versus 25%), fall risk (82% versus 35%), and cognitive impairment (72% versus 28%). Rates of antipsychotic polypharmacy were also six times higher in the TAU group. CONCLUSION: Older patients with schizophrenia treated with antipsychotics within an ICP experience higher rates of monitoring and less psychotropic polypharmacy than older patients treated with antipsychotics under TAU conditions. These findings suggest that an ICP can improve the quality of antipsychotic pharmacotherapy in older patients and thus possibly its effectiveness. This needs to be confirmed by a randomized controlled trial.

Fahr's syndrome in Southern Tunisia: A broad spectrum of clinical and etiological features.

AIM: We describe the clinical and etiological profile of patients with Fahr's syndrome (FS). METHODS: Charts of sixteen patients diagnosed with FS between 1999 and 2014 were retrospectively assessed. RESULTS:   The mean age at diagnosis was 44.68 years (11-67 years). The most main presenting neurological features were seizures in 6 cases, headaches in 5 cases and parkinson's syndrome in 3 cases. Psychiatric disorders were observed in 2 patients including memory loss and iritability. Hypocalcemia clinical features were observed in 7 cases. The mean value of hypocalcemia was 1.69 mmol/l. Etiologies included idiopathic hypoparathyroidism in 4 patients, pseudohypoparathyroidism in 5 cases, secondary hypoparathyroidism, isolated hypovitaminosis D and cerebral radiotherapy in one case for each and Fahr's disease in 4 patients.  Oral calcium and vitamin D substitution were started in patients with parathyroid disturbances with favorable outcome. CONCLUSION: In this report, we propose to discuss the clinical manifestations of FS, its etiologies especially parathyroid disturbances and its therapeutic modalities.

Association of Antidepressant Use With Drug-Related Extrapyramidal Symptoms: A Pharmacoepidemiological Study.

BACKGROUND: Antidepressants are one of the most prescribed classes of medications. A number of case reports have linked these drugs to extrapyramidal symptoms (EPSs), but no large epidemiologic study to date has examined this association. We sought to quantify the association of EPSs with different antidepressants by undertaking a large pharmacoepidemiologic study. METHODS: A nested case-control study was conducted using a large health claims database in the United States from June 2006 to December 2015. Subjects with a diagnosis of primary Parkinson disease and those who received prescriptions of levodopa, ropinirole, pramipexole, domperidone, metoclopramide, entacapone, benztropine, selegiline, rasagiline, diphenhydramine, trihexyphenidyl, typical and atypical antipsychotics, and tricyclic antidepressants were excluded. Cases were followed to the first billing code for an extrapyramidal event or last date of enrollment in the cohort. For each case, 10 control subjects were matched by follow-up time, calendar time, and age through density-based sampling. Rate ratios were computed using conditional logistic regression adjusting for other covariates. RESULTS: We identified 3,838 subjects with EPSs compared with 38,380 age-matched control subjects. Rate ratios with respect to EPSs were as follows: duloxetine, 5.68 (95% confidence interval [CI], 4.29-7.53); mirtazapine, 3.78 (95% CI, 1.71-8.32); citalopram, 3.47 (95% CI, 2.68-4.50); escitalopram, 3.23 (95% CI, 2.44-4.26); paroxetine, 3.07 (95% CI, 2.15-4.40); sertraline, 2.57 (95% CI, 2.02-3.28); venlafaxine, 2.37 (95% CI, 1.71-3.29); bupropion, 2.31 (95% CI, 1.67-3.21); and fluoxetine, 2.03 (95% CI, 1.48-2.78). CONCLUSIONS: This observational study demonstrates a harmful association between the incidence of Parkinson disease or associated EPSs and use of the antidepressants duloxetine, mirtazapine, citalopram, escitalopram, paroxetine, sertraline, venlafaxine, bupropion, and fluoxetine.