Neuropsychiatric Signs Research Articles

Weight Loss in Patients with Dementia: Considering the Potential Impact of Pharmacotherapy.

Unintentional body weight loss is common in patients with dementia and is linked to cognitive impairment and poorer disease outcomes. It is proposed that some dementia medications with market approval, while aiming to improve cognitive and functional outcomes of a patient with dementia, are associated with reported body weight or body mass index loss. This review presents evidence in the published literature on body weight loss in dementia, describes selected theories behind body weight loss, evaluates the potential impact of approved dementia pharmacotherapies on body weight, considers the potential role for medical foods, understands the potential influence of treatments for neuropsychiatric symptoms and signs, and finally, summarizes this important area.

Hashimoto Encephalopathy with polymorphic neuropsychiatric signs: a case report

Hashimoto Encephalopathy with polymorphic neuropsychiatric signs: a case report

한의병증에 대한 신경정신과적 증상 기술 연구

한의병증에 대한 신경정신과적 증상 기술 연구

THE ANALYSIS OF CARBON MONOXIDE POISONING CASES PRESENTED TO THE EMERGENCY DEPARTMENT OF A UNIVERSITY HOSPITAL

Introduction : Carbon monoxide poisoning is one of the most leading poisoning causing death through worldwide, although its exact incidence is yet to be determined. Carbon monoxide is a colorless and odorless gas that binds to hemoglobin and cellular oxidative enzymes with a higher affinity than oxygen, causing tissue hypoxia. Hypoxia of heart and nervous system cells leads to neuropsychiatric and cardiological signs and symptoms. In this study, we aimed to investigate the demographic characteristics of the carbon monoxide poisonings occurring in patients presenting to the emergency department. We also aimed to determine the clinical characteristics, and the factors affecting the mortality. Material and Methods : We retrospectively reviewed the demographic and clinical characteristics of 1013 patients who admitted to our adult emergency department and were diagnosed with carbon monoxide poisoning for a period of two years. We recorded and analyzed age, gender, season of presentation, hospital admission rate, sources of poisoning, symptoms at admission, mortality rate, and carboxyhemoglobin and cardiac Troponin-I levels. Results : The mean age of the study population was 36.2±16.2 years. 70.5% of the patients were admitted in winter seasons. 66.1% of the patients’ poisoning source was water heater and stove. The most frequent symptoms were nausea, headache, and dizziness. On multilogistic regression analysis the death rate was significantly correlated with age and cardiac Troponin I level. Conclusion : Our results indicate that accidental carbon monoxide poisonings continue to be an important public health problem in regions with cold winter seasons. We believe that intensifying efforts for public education and efficient control of resources of poisoning are the key steps to prevent carbon monoxide poisonings.

"I swear it is Tourette's!": On functional coprolalia and other tic-like vocalizations.

Coprolalia in neuropsychiatry is typically associated with tic disorders, in particular Gilles de la Tourette syndrome. To date, there has been no report of functional coprolalia. Here, we provide the clinical characteristics of 13 adolescent and adult patients with coprolalic and other functional tic-like complex vocalizations who, on the basis of these symptoms, were misdiagnosed with a primary tic disorder, most commonly Gilles de la Tourette syndrome. We describe similarities and highlight the differences from primary tic disorders in order to provide a pragmatic list of clinical clues that will facilitate correct diagnostic labeling and thereby treatment. Finally, we emphasize that the distinction between a primary and a functional tic disorder should rely on a combination of neuropsychiatric symptoms and signs and not on the presence of single, however striking, abnormal behaviors, such as coprolalia.

Analysis of Mutations in AARS2 in a Series of CSF1R-Negative Patients With Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a frequent cause of adult-onset leukodystrophy known to be caused by autosomal dominant mutations in the CSF1R (colony-stimulating factor 1) gene. The discovery that CSF1R mutations cause ALSP led to more accurate prognosis and genetic counseling for these patients in addition to increased interest in microglia as a target in neurodegeneration. However, it has been known since the discovery of the CSF1R gene that there are patients with typical clinical and radiologic evidence of ALSP who do not carry pathogenic CSF1R mutations. These patients include those in whom the pathognomonic features of axonal spheroids and pigmented microglia have been found. Achieving a genetic diagnosis in these patients is important to our understanding of this disorder. To genetically characterize a group of patients with typical features of ALSP who do not carry CSF1R mutations. In this case series study, 5 patients from 4 families were identified with clinical, radiologic, or pathologic features of ALSP in whom CSF1R mutations had been excluded previously by sequencing. Data were collected between May 2014 and September 2015 and analyzed between September 2015 and February 2016. Focused exome sequencing was used to identify candidate variants. Family studies, long-range polymerase chain reaction with cloning, and complementary DNA sequencing were used to confirm pathogenicity. Of these 5 patients, 4 were men (80%); mean age at onset of ALSP was 29 years (range, 15-44 years). Biallelic mutations in the alanyl-transfer (t)RNA synthetase 2 (AARS2) gene were found in all 5 patients. Frameshifting and splice site mutations were common, found in 4 of 5 patients, and sequencing of complementary DNA from affected patients confirmed that the variants were loss of function. All patients presented in adulthood with prominent cognitive, neuropsychiatric, and upper motor neuron signs. Magnetic resonance imaging in all patients demonstrated a symmetric leukoencephalopathy with punctate regions of restricted diffusion, typical of ALSP. In 1 patient, brain biopsy demonstrated axonal spheroids and pigmented microglia, which are the pathognomonic signs of ALSP. This work indicates that mutations in the tRNA synthetase AARS2 gene cause a recessive form of ALSP. The CSF1R and AARS2 proteins have different cellular functions but overlap in a final common pathway of neurodegeneration. This work points to novel targets for research and will lead to improved diagnostic rates in patients with adult-onset leukoencephalopathy.

Neuropsychiatric manifestations of vitamin B12 and folate deficiencies: Data from an inpatient psychiatric department

IntroductionThe prevalence of vitamin B12 and folate deficiency is significant in the psychiatric population. These deficiencies may be associated with varied neuropsychiatric signs and symptoms, caused by different pathophysiological mechanisms.ObjectivesCharacterize the main neuropsychiatric signs and symptoms associated with vitamin B12 and folate deficiencies. Evaluate the prevalence of these vitamins deficiencies in an acute inpatient psychiatric department, dedicated to Affective Disorders.AimsTo review the clinical significance of vitamin B12 and folate deficiencies in psychiatric disorders and reflect on the importance of routine screening in mental health care.Material and methodsObservational, retrospective and descriptive study, with analysis of clinical and blood tests data concerning the total number of inpatient episodes in 2015. Non-systematic review of the scientific literature.ResultsA small case series of the patients that had folate or B12 deficiency detected is presented. The prevalence of vitamin B12 and folate deficiencies found in our study is in accordance with the data found in the literature.ConclusionsVitamin B12 and folate deficiencies should be considered in the approach to the psychiatric patient as its neuropsychiatric manifestations are varied, can be severe, and may constitute a potentially treatable cause of mental disorder. Our data shows that folate and B12 deficiencies are significant in inpatients and we believe it justifies routine screening at admission.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Pharmacologic and nonpharmacologic approaches to the prevention and management of delirium.

Delirium is a syndrome of neuropsychiatric signs and symptoms that can accompany virtually any serious medical condition. Delirium is characterized by a disturbance of attention and awareness, as well as variety of other aspects of cognition that develops over a short period of time in response to another medical condition. It is an independent risk factor for increased morbidity and mortality and is associated with increased lengths of stay and costs of care. Despite this, it frequently goes unrecognized, and debate continues about the best prevention and treatment strategies. This article will review the current best practices for the prevention and treatment of delirium and how collaborative care can aid in improving outcomes and minimizing adverse events for patients suffering from delirium.

Parkinsonism as a Manifestation of Neuropsychiatric Systemic Lupus Erythematosus: A Case Report and Literature Review

Involvement of the central nervous system in systemic lupus erythematosus has been well documented. Parkinsonism as a manifestation of central nervous system lupus is rare. In this article, we report a 17-year-old girl who developed parkinsonism within one month of the onset of systemic lupus erythematosus, and presented with expressionless facies, bradykinesia, marked rigidity, and hypermyotonia. Magnetic resonance imaging showed abnormity in bilateral basal ganglia, external capsule, insular lobe, and lateral hippocampus symmetrically. Methylprednisolone pulse therapy, intravenous cyclophosphamide, and intrathecal injection of methotrexate plus dexamethasone were prescribed. Two months later, the patient returned with complete clinical recovery of neuropsychiatric symptoms and signs.

Hereditary leukoencephalopathy with axonal spheroids: a spectrum of phenotypes from CNS vasculitis to parkinsonism in an adult onset leukodystrophy series

BackgroundHereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a hereditary, adult onset leukodystrophy which is characterised by the presence of axonal loss, axonal spheroids and variably present pigmented macrophages on...

P176 – 2905: Neurological manifestations and clinical outcomes of Hashimoto thyroiditis in children

Objective Hashimoto thyroiditis (HT) is an autoimmune thyroid disease, characterized by different clinical courses and presentation. The purpose of this study was to identify the neurological manifestations of Hashimoto thyroiditis in children and evaluate their clinical outcome. Methods Fifteen patients under monitoring with a diagnosis of HT and also presenting with neurological manifestations were enrolled in the study. Patients presenting with change of consciousness was considered as Hashimoto's encephalopathy. Clinical outcomes were assessed by most recent neurological examinations during their visit at our pediatric neurology department. Results The study patients consisted of 2 boys and 13 girls. The mean age at diagnosis of patients was 12.8±2.83 years (age range, 6–17 years). The mean duration of follow-up was 25.8±12.7 months, and ranged from 6–48 months. At the time of presentation; 5 patients were euthyroid, and 10 was hypothyroid. Neurological findings at presentation included: headache in 10 patients, epileptic seizures in 5 patients, focal paresis in 4 patients, speech abnormalities in 3 patients, decreased school performance in 2 patients, ataxia in 2 patients, Hashimoto's encephalopathy in 2 patients, diplopia in 1 patients, status epilepticus in 1 patients, and coma in 1 patients. Abnormal electroencephalographic recordings revealed in 8 patients. All hypothyroid patients received thyroxine replacement therapy. Two patients received intravenous methylprednisolone, and 1 patient took intravenous immunoglobulin treatment. Four children received antiepileptic therapy for control of epileptic seizures. Four children improved spontaneously without any treatment. In contrast, Hashimoto's encephalopathy relapsed 6 times despite all the treatments in 1 patient during follow up period. Conclusion Hashimoto thyroiditis should be considered in any patient presenting with unexplained neuropsychiatric signs and symptoms.

Long-term and low-dose malathion exposure causes cognitive impairment in adult mice: evidence of hippocampal mitochondrial dysfunction, astrogliosis and apoptotic events

The organophosphorus (OP) pesticide malathion is a neurotoxic compound whose acute toxicity is primarily caused by the inhibition of acetylcholinesterase (AChE), leading to cholinergic syndrome-related symptoms. Some lines of evidence indicate that long-term exposure to low levels of OP may produce neuropsychiatric and/or neurobehavioral signs that do not necessarily involve the AChE inhibition. This study evaluated the effects of a repeated (15-day period) and low-dose malathion exposure on spatial memory and discrimination (object location task), as well as on biochemical parameters in the hippocampus of mice [AChE and mitochondrial chain complexes activities; levels of proapoptotic proteins (Bax and Bak) and cholinergic neuronal and astroglial markers (ChAT and GFAP, respectively)]. Malathion treatments (30 and 100 mg/kg, s.c.) did not affect the body weight of animals and caused no evident signs of cholinergic toxicity throughout the treatment, although the highest dose (100 mg/kg) was associated with inhibition of AChE activity. Malathion-exposed animals showed a significant impairment on spatial memory and discrimination, which was correlated with a decrease in the mitochondrial complex I activity in the hippocampus. Moreover, malathion increased the levels of proapoptotic proteins and induced astroglial activation. The results show that long-term malathion exposure, at a dose that does not affect hippocampal AChE activity (30 mg/kg), caused impaired spatial memory and discrimination in mice that was related to hippocampal mitochondrial dysfunctional, astrogliosis and apoptosis. When extrapolated to humans, such results shed light on noncholinergic mechanisms likely related to the neurobehavioral and cognitive deficits observed in individuals chronically exposed to this pesticide.

Depressive-like behavior is paired to monoaminergic alteration in a murine model of Alzheimer's disease.

Background:Neuropsychiatric signs are critical in primary caregiving of Alzheimer patients and have not yet been fully inves tigated in murine models.Methods:18-month-old 3×Tg-AD male mice and their wild-type male littermates (non-Tg) were used. The open field test and the elevated plus maze test were used to evaluate anxiety-like behaviors, whereas the Porsolt forced swim test, the tail suspension test, and the sucrose preference test for antidepressant/depression-coping behaviors. Neurochemical study was conducted by microdialysis in freely-moving mice, analyzing the basal and K+-stimulated monoamine output in the frontal cortex and ventral hippocampus. Moreover by immunohistochemistry, we analysed the expression of Tyrosin hydroxylase and Tryptophan hydroxylase, which play a key role in the synthesis of monoamines.Results:Aged 3×Tg-AD mice exhibited a higher duration of immobility in the forced swim and tail suspension tests (predictors of depression-like behavior) which was not attenuated by a noradrenaline reuptake inhibitor, desipramine. In the sucrose preference test, 3×Tg-AD mice showed a significantly lower sucrose preference compared to the non-Tg group, without any difference in total fluid intake. In contrast, the motor functions and anxiety-related emotional responses of 3×Tg-AD mice were normal, as detected by the open-field and elevated plus-maze tests. To strengthen these results, we then evaluated the monoaminergic neurotransmissions by in vivo microdialysis and immunohistochemistry. In particular, with the exception of the basal hippocampal dopamine levels, 3×Tg-AD mice exhibited a lower basal extracellular output of amines in the frontal cortex and ventral hippocampus and also a decreased extracellular response to K+ stimulation. Such alterations occur with obvious local amyloid-β and tau pathologies and without gross alterations in the expression of Tyrosin and Tryptophan hydroxylase.Conclusions:These results suggest that 3×Tg-AD mice exhibit changes in depression-related behavior involving aminergic neurotrasmitters and provide an animal model for investigating AD with depression.

Psychiatric signs and symptoms in treatable inborn errors of metabolism

Possible underlying organic causes of psychiatric symptoms can be overlooked in the clinical setting. It is important to increase awareness amongst psychiatric and neurological professionals with regard to certain inborn errors of metabolism as, in some cases, disease-specific therapies are available that can, for instance, treat underlying metabolic causes. The following article describes the basic pathophysiology, clinical and neurological features, and available diagnostic procedures of six treatable metabolic diseases that are associated with neuropsychiatric symptoms: Wilson’s disease, cerebrotendinous xanthomatosis, porphyrias, homocysteinemia, urea cycle disorders, and Niemann-Pick disease type C (NP-C). NP-C is taken as a particularly relevant example because, while it is traditionally considered to be a condition that presents with severe neurological and systemic manifestations in children, an increasing number of patients are being detected who have the adolescent- or adult-onset form, which is frequently associated with neuropsychiatric signs. A notable proportion of adult-onset cases have been reported where NP-C has mistakenly been diagnosed and treated as a psychiatric condition, usually based on patients’ initial presentation with psychotic or schizophrenia-like symptoms. Underlying organic causes of psychiatric disorders such as psychosis should be considered among patients with atypical symptoms and/or resistance to standard therapy. Alongside improved frameworks for additional multidisciplinary diagnostic work in patients with suspected organic disease, the development of convenient and affordable biochemical screening and/or diagnostic methods has enabled new ways to narrow down differential diagnoses.

Niemann-Pick disease type C: introduction and main clinical features.

Niemann-Pick disease type C: introduction and main clinical features.

Progressive neuropsychiatric manifestations of phenylketonuria in adulthood

IntroductionNeuropsychiatric signs and MRI abnormalities can occur in patients with phenylketonuria in adulthood. We describe clinical and radiological features of phenylketonuric patients and we discuss the advantage of continuing diet in adulthood. MethodWe report late onset neuropsychiatric symptoms of four phenylketonuric patients (33–45years) diagnosed in infancy and report the case of a patient (33years) diagnosed with phenylketonuria because of late onset neurological signs. We describe clinical and radiological features of these 5 patients, and their evolution under diet and propose a review of the literature. ResultsThe main neurological abnormalities in phenylketonuric patients diagnosed in infancy are: brisk reflexes, spastic paraparesis, psychiatric signs that appear 10.5years after the diet arrest. A leukoencephalopathy was present in 93% of cases and 91.7% improve clinically after poor phenylalanine diet reintroduction. In 4 patients, neurological abnormalities (spastic paraparesis, dementia, Parkinsonism) led to the late diagnosis. Two of them had a leukoencephalopathy on brain MRI. Patients had high levels of phenylalanine (above 1500μmol/L) when neuropsychiatric signs occurred. Improvement after diet suggests that hyperphenylalaninemia has a direct toxic effect on the brain. Discussion/ConclusionThe long-term follow-up of phenylketonuric patients is mandatory to depict and treat neurological complications in time. Diet reintroduction is efficacious in most cases.

The Involvement of Secondary Neuronal Damage in the Development of Neuropsychiatric Disorders Following Brain Insults

Neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people. Previous publications have demonstrated that neuropsychiatric disorders can cause histomorphological damage in particular regions of the brain. By using a clinical symptom-comparing approach, 55 neuropsychiatric signs or symptoms related usually to 14 types of acute and chronic brain insults were identified and categorized in the present study. Forty percent of the 55 neuropsychiatric signs and symptoms have been found to be commonly shared by the 14 brain insults. A meta-analysis supports existence of the same neuropsychiatric signs or symptoms in all brain insults. The results suggest that neuronal damage might be occurring in the same or similar regions or structures of the brain. Neuronal cell death, neural loss, and axonal degeneration in some parts of the brain (the limbic system, basal ganglia system, brainstem, cerebellum, and cerebral cortex) might be the histomorphological basis that is responsible for the neuropsychiatric symptom clusters. These morphological alterations may be the result of secondary neuronal damage (a cascade of progressive neural injury and neuronal cell death that is triggered by the initial insult). Secondary neuronal damage causes neuronal cell death and neural injury in not only the initial injured site but also remote brain regions. It may be a major contributor to subsequent neuropsychiatric disorders following brain insults.

Abstract W P227: Cerebral Hyperperfusion Syndrome after Intravenous Thrombolysis for Acute Ischemic Stroke

Background: Cerebral hyperperfusion syndrome (CHS) is a recognized complication after surgical revascularization of a chronically atherosclerotic artery. However, this phenomenon is unexpected when an acutely occluded artery is recanalized by IV-TPA for acute ischemic stroke (AIS).In patients with discrepant neuroimaging and clinical findings, our multimodal evaluations revealed CHS in a series of 7 patientsmafter IV- TPA therapy. Methods: Patients in whom the occluded ICA or MCA in pre-TPA CT-angiogram (CTA) showed recanalization in the day-2 CTA, were observed for any new unexpected neuropsychiatric symptoms/signs. If these were present they underwent multimodal evaluation including serial transcranial Doppler (TCD), quantitative electroencephalography (QEEG) and HMPAO-SPECT. Patients with considerable mismatch between clinical and neuroimaging findings were also included. CHS was deemed to have occurred if the unexpected neuropsychiatric signs corresponded with TCD flow velocity >100% of the contralateral vessel, EEG showed abnormal activity and HMPAO-SPECT scan showed markedly increased cerebral perfusion compared to the contralateral side. Results: Out of 155 patients treated with IV-TPA, 7 (4.5%) patients fulfilled our definition of CHS. All 7 patients developed the symptoms 2-3 days after IV-TPA. Abnormalities on TCD, QEEG and HMPAO-SPECT were observed in all patients. The unexpected symptoms included generalized headache (4 cases), unexplained persistent drowsiness (3 cases), visual neglect (2 cases), aphasia (2 cases) and severe suicidal thoughts despite complete neurological recovery (1 case). All cases had hypertension prior to the index stroke. Upright posture, fluid restriction and aggressive blood pressure control resulted in rapid resolution of abnormal features in all cases within a week. All patients achieved modified Rankin score 0-1 with no intracranial hemorrhage. Conclusion: CHS after intravenous thrombolysis in acute ischemic stroke should be suspected in patients that achieve arterial recanalization with unexplained new neuropsychiatric manifestations. Early diagnosis and appropriate management might prevent hemorrhage and achieve good functional outcomes.

Heterogeneity and frequency of movement disorders in juvenile and adult-onset Niemann-Pick C disease

Niemann-Pick type C disease (NPC) is a recessive neurolipidosis. We report five adolescent and adult NPC cases to underscore the frequency and heterogeneity of movement disorders in NPC. Clinical, morphologic, biochemical and genetic study was performed in the five patients. Disease onset was between 8 and 50 years. Movement disorders were present in all cases, were heterogeneous and often combined [cerebellar ataxia (5/5), myoclonus (3/5), dystonia (2/5), chorea (1/5) and tremor (1/5)] and were the first sign in 4/5. Two patients were reported to have no vertical supranuclear gaze palsy (VSGP) at the first examination. Two patients experienced acute neuropsychiatric signs leading to death in one case due to myoclonic storm. Filipin staining was always positive. Two NPC1 mutations were identified in three patients, only one in two siblings. NPC should be considered in case of unexplained movement disorders, even when VSGP or cataplexy are not reported. Filipin staining remains a strong support for the diagnosis. Treatment with miglustat should be considered which is currently the only approved disease-specific treatment of NPC in children and adults.

Delirium as a result of vitamin B12 deficiency in a vegetarian female patient

Vitamin B12 deficiency can manifest with haematological, gastrointestinal and neuropsychiatric signs. The neuropsychiatric symptoms may be concurrent or precede the other symptoms. The reported case is a clinical case of delirium due to vitamin B12 deficiency in a female vegetarian patient. The patient was treated with vitamin B12 supplementation. Initially, it was difficult to diagnose this patient, who presented with delirium that could have been due to multiple causes. The finding underlines the importance of conducting a complete laboratory test panel for delirium, including the blood levels of vitamin B12.