scholarly journals CADASIL syndrome (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) presenting as psychosis

2018 ◽  
Vol 31 (3) ◽  
pp. e100017 ◽  
Author(s):  
Dheerendra Kumar Mishra ◽  
Aman Kishore ◽  
Vijay Niranjan
Keyword(s):  
Autosomal Dominant ◽  
Small Vessel Disease ◽  
Significant Proportion ◽  
Psychotic Symptoms ◽  
Behavioural Disturbance ◽  
Monogenic Form ◽  
Recurrent Strokes ◽  
Spectrum Disorders ◽  
Psychotic Features ◽  
Subcortical Infarct

Cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) is the most common monogenic form of cerebral small-vessel disease characterised by recurrent strokes. Behavioural disturbance also presents in a significant proportion of subjects as neurotic spectrum disorders and psychotic features are rarely reported. In this case report, we highlight a 32-year-old man with CADASIL syndrome, who had overt psychotic symptoms with neurological signs later on.

Psychosis and longitudinal outcomes in Huntington disease: the COHORT Study

2019 ◽  
Vol 91 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Michael H Connors ◽  
Armando Teixeira-Pinto ◽  
Clement T Loy
Keyword(s):  
Huntington Disease ◽  
Autosomal Dominant ◽  
Clinical Course ◽  
Psychiatric Symptoms ◽  
Significant Proportion ◽  
Observational Research ◽  
Psychotic Symptoms ◽  
Behavioural Disturbance ◽  
Longitudinal Outcomes ◽  
Motor Disturbances

ObjectiveHuntington disease (HD) is an autosomal dominant neurodegenerative disease involving motor disturbances, cognitive decline and psychiatric symptoms. Psychotic symptoms occur in a significant proportion of patients. We sought to characterise the clinical outcomes of this group of patients.MethodsData were drawn from the Cooperative Huntington Observational Research Trial, a prospective, multi-centre observational study. 1082 patients with HD were recruited. Measures of cognition, function, behavioural disturbance and motor function were completed annually over 5 years.ResultsOverall, 190 patients (17.6%) displayed psychotic symptoms. These patients demonstrated worse cognition, function and behavioural disturbances than patients without psychosis over time. Patients with psychosis also demonstrated lower levels of chorea than patients without psychosis, despite adjusting for concurrent antipsychotic and tetrabenazine use.ConclusionsPsychosis in HD is associated with poorer outcomes in cognition, function and behavioural symptoms. Patients with psychotic symptoms may also have less chorea. Altogether, the findings suggest patients with psychosis have a distinct clinical course.

scholarly journals Ischemic Stroke in a Patient with Stable CADASIL during COVID-19: A Case Report

2021 ◽  
Vol 11 (12) ◽  
pp. 1615
Author(s):  
Alessandro Cruciani ◽  
Fabio Pilato ◽  
Mariagrazia Rossi ◽  
Francesco Motolese ◽  
Vincenzo Di Lazzaro ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Endothelial Dysfunction ◽  
Autosomal Dominant ◽  
Small Vessel Disease ◽  
Stroke Recurrence ◽  
Vessel Disease ◽  
Increased Risk ◽  
Recurrent Strokes ◽  
Neurological Conditions ◽  
Guillain Barré

Background: SARS-CoV-2 infection has been associated with different neurological conditions such as Guillain-Barré, encephalitis and stroke. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small-vessel disease characterized by recurrent ischemic stroke, cognitive decline, migraine and mood disturbances. One of the mechanisms involved in CADASIL pathogenesis is endothelial dysfunction, which causes an increased risk of recurrent strokes. Since COVID-19 infection is also associated with coagulopathy and endothelial dysfunction, the risk of ischemic stroke might be even higher in this population. We describe the case of a CADASIL patient who developed an acute ischemic stroke after SARS-CoV-2 infection. In patients with diseases causing endothelial dysregulation, such as CADASIL, the hypercoagulability related to COVID-19 may contribute to the risk of stroke recurrence.

Early-onset vascular leukoencephalopathy caused by bi-allelic NOTCH3 variants

2022 ◽  
Author(s):  
Menno Stellingwerff ◽  
Corinne Nulton ◽  
Guy Helman ◽  
Stefan Roosendaal ◽  
William Benko ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Small Vessel Disease ◽  
Cerebral White Matter ◽  
Allelic Loss ◽  
Early Age ◽  
Loss Of Function ◽  
Mri Findings ◽  
Temporal Lobes ◽  
Recurrent Strokes ◽  
Clinical Records

Objective Heterozygous NOTCH3 variants are known to cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), with patients typically presenting in adulthood. We describe three patients presenting at an early age with a vascular leukoencephalopathy. Genome sequencing revealed bi-allelic variants in the NOTCH3 gene. Methods Clinical records and available MRI and CT scans of three patients from two unrelated families were retrospectively reviewed. Results The patients presented at 9-14 months of age with developmental delay, seizures, or both. The disease course was characterized by cognitive impairment and variably recurrent strokes, migraine attacks, and seizures. MRI findings pointed at a small vessel disease, with extensive cerebral white matter abnormalities, atrophy, lacunes in the basal ganglia, microbleeds and microcalcifications. The anterior temporal lobes were spared. Bi-allelic cysteine-sparing NOTCH3 variants in exons 1, 32 and 33 were found. Interpretation This study indicates that bi-allelic loss-of-function NOTCH3 variants may cause a vascular leukoencephalopathy, distinct from CADASIL.

Cerebrovascular and Neurodegenerative Pathologies in Long-Term Stable Mild Cognitive Impairment

2021 ◽  
pp. 1-15
Author(s):  
Manu J. Sharma ◽  
Brandy L. Callahan
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cerebral Amyloid Angiopathy ◽  
Neurofibrillary Tangles ◽  
Small Vessel Disease ◽  
Significant Proportion ◽  
Amyloid Angiopathy ◽  
Prodromal Phase ◽  
Cerebral Amyloid

Background: Mild cognitive impairment (MCI) is considered by some to be a prodromal phase of a progressive disease (i.e., neurodegeneration) resulting in dementia; however, a substantial portion of individuals (ranging from 5–30%) remain cognitively stable over the long term (sMCI). The etiology of sMCI is unclear but may be linked to cerebrovascular disease (CVD), as evidence from longitudinal studies suggest a significant proportion of individuals with vasculopathy remain stable over time. Objective: To quantify the presence of neurodegenerative and vascular pathologies in individuals with long-term (>5-year) sMCI, in a preliminary test of the hypothesis that CVD may be a contributor to non-degenerative cognitive impairment. We expect frequent vasculopathy at autopsy in sMCI relative to neurodegenerative disease, and relative to individuals who convert to dementia. Methods: In this retrospective study, using data from the National Alzheimer’s Coordinating Center, individuals with sMCI (n = 28) were compared to those with MCI who declined over a 5 to 9-year period (dMCI; n = 139) on measures of neurodegenerative pathology (i.e., Aβ plaques, neurofibrillary tangles, TDP-43, and cerebral amyloid angiopathy) and CVD (infarcts, lacunes, microinfarcts, hemorrhages, and microbleeds). Results: Alzheimer’s disease pathology (Aβ plaques, neurofibrillary tangles, and cerebral amyloid angiopathy) was significantly higher in the dMCI group than the sMCI group. Microinfarcts were the only vasculopathy associated with group membership; these were more frequent in sMCI. Conclusion: The most frequent neuropathology in this sample of long-term sMCI was microinfarcts, tentatively suggesting that silent small vessel disease may characterize non-worsening cognitive impairment.

scholarly journals Acoustic speech markers for schizophrenia-spectrum disorders: a diagnostic and symptom-recognition tool

2021 ◽  
pp. 1-11
Author(s):  
J. N. de Boer ◽  
A. E. Voppel ◽  
S. G. Brederoo ◽  
H. G. Schnack ◽  
K. P. Truong ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Structured Interview ◽  
Diagnostic Value ◽  
Spectrum Disorder ◽  
Psychotic Symptoms ◽  
Schizophrenia Spectrum Disorders ◽  
Schizophrenia Spectrum Disorder ◽  
Speech Technology ◽  
Schizophrenia Spectrum ◽  
Spectrum Disorders

Abstract Background Clinicians routinely use impressions of speech as an element of mental status examination. In schizophrenia-spectrum disorders, descriptions of speech are used to assess the severity of psychotic symptoms. In the current study, we assessed the diagnostic value of acoustic speech parameters in schizophrenia-spectrum disorders, as well as its value in recognizing positive and negative symptoms. Methods Speech was obtained from 142 patients with a schizophrenia-spectrum disorder and 142 matched controls during a semi-structured interview on neutral topics. Patients were categorized as having predominantly positive or negative symptoms using the Positive and Negative Syndrome Scale (PANSS). Acoustic parameters were extracted with OpenSMILE, employing the extended Geneva Acoustic Minimalistic Parameter Set, which includes standardized analyses of pitch (F0), speech quality and pauses. Speech parameters were fed into a random forest algorithm with leave-ten-out cross-validation to assess their value for a schizophrenia-spectrum diagnosis, and PANSS subtype recognition. Results The machine-learning speech classifier attained an accuracy of 86.2% in classifying patients with a schizophrenia-spectrum disorder and controls on speech parameters alone. Patients with predominantly positive v. negative symptoms could be classified with an accuracy of 74.2%. Conclusions Our results show that automatically extracted speech parameters can be used to accurately classify patients with a schizophrenia-spectrum disorder and healthy controls, as well as differentiate between patients with predominantly positive v. negatives symptoms. Thus, the field of speech technology has provided a standardized, powerful tool that has high potential for clinical applications in diagnosis and differentiation, given its ease of comparison and replication across samples.

scholarly journals Contribution of “Omic” Studies to the Understanding of Cadasil. A Systematic Review

2021 ◽  
Vol 22 (14) ◽  
pp. 7357
Author(s):  
Elena Muiño ◽  
Israel Fernández-Cadenas ◽  
Adrià Arboix
Keyword(s):  
Growth Factor ◽  
Protein Misfolding ◽  
Drug Targets ◽  
Transforming Growth Factor ◽  
Small Vessel Disease ◽  
Transforming Growth Factor Β ◽  
Small Vessel ◽  
Vessel Disease ◽  
Extracellular Matrix Components ◽  
Recurrent Strokes

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a small vessel disease caused by mutations in NOTCH3 that lead to an odd number of cysteines in the epidermal growth factor (EGF)-like repeat domain, causing protein misfolding and aggregation. The main symptoms are migraines, psychiatric disorders, recurrent strokes, and dementia. Omic technologies allow the massive study of different molecules for understanding diseases in a non-biased manner or even for discovering targets and their possible treatments. We analyzed the progress in understanding CADASIL that has been made possible by omics sciences. For this purpose, we included studies that focused on CADASIL and used omics techniques, searching bibliographic resources, such as PubMed. We excluded studies with other phenotypes, such as migraine or leukodystrophies. A total of 18 articles were reviewed. Due to the high prevalence of NOTCH3 mutations considered pathogenic to date in genomic repositories, one can ask whether all of them produce CADASIL, different degrees of the disease, or whether they are just a risk factor for small vessel disease. Besides, proteomics and transcriptomics studies found that the molecules that are significantly altered in CADASIL are mainly related to cell adhesion, the cytoskeleton or extracellular matrix components, misfolding control, autophagia, angiogenesis, or the transforming growth factor β (TGFβ) signaling pathway. The omics studies performed on CADASIL have been useful for understanding the biological mechanisms and could be key factors for finding potential drug targets.

scholarly journals HNF1α mutations are present in half of clinically defined MODY patients in South-Brazilian individuals

2008 ◽  
Vol 52 (8) ◽  
pp. 1326-1331 ◽  
Author(s):  
Jorge de Faria Maraschin ◽  
Caroline Kannengiesser ◽  
Nádia Murussi ◽  
Nicole Campagnolo ◽  
Luís Henrique Canani ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Age Of Onset ◽  
Pancreatic Beta Cell ◽  
Early Age ◽  
Hepatocyte Nuclear Factor ◽  
Cell Dysfunction ◽  
Monogenic Form ◽  
Hepatocyte Nuclear Factor 1Α ◽  
Relative Prevalence ◽  
Clinical Diagnostic Criteria

Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset, and pancreatic beta cell dysfunction. Heterozygous mutations in at least seven genes can cause MODY. In the present study we investigated the relative prevalence of GCK (glucokinase) and HNF1α (hepatocyte nuclear factor 1α) mutations, the more frequent causes of MODY, in 13 South-Brazilian families with multiple cases of diabetes consistent with MODY. Heterozygous variants in GCK and HNF1α genes were observed respectively in one (7.7%), and six (46.2%) families. The six HNF1α variants are likely to cause diabetes in the families where they were observed. However, we could not ascertain whether the GCK Gly117Ser variant found in one family is a causal mutation. In conclusion, we have confirmed in a South-Brazilian population that HNF1α mutations are a common cause of monogenic diabetes in adults selected with strict clinical diagnostic criteria.

scholarly journals The Genetics of Monogenic Frontotemporal Dementia

2015 ◽  
Vol 9 (3) ◽  
pp. 219-229 ◽  
Author(s):  
Leonel T. Takada
Keyword(s):  
Frontotemporal Dementia ◽  
Autosomal Dominant ◽  
Positive Family History ◽  
Chromosome 9 ◽  
Complex Phenotype ◽  
Reading Frame ◽  
Protein Tau ◽  
Paget Disease ◽  
Fused In Sarcoma ◽  
Spectrum Disorders

ABSTRACT Around 10-15% of patients diagnosed with frontotemporal dementia (FTD) have a positive family history for FTD with an autosomal dominant pattern of inheritance. Since the identification of mutations in MAPT(microtubuleassociated protein tau gene) in 1998, over 10 other genes have been associated with FTD spectrum disorders, discussed in this review. Along with MAPT, mutations in GRN(progranulin) and C9orf72(chromosome 9 open reading frame 72) are the most commonly identified in FTD cohorts. The association of FTD and motor neuron disease (MND) can be caused by mutations in C9orf72and other genes, such as TARDBP(TAR DNA-binding protein), FUS(fused in sarcoma), UBQLN2(ubiquilin 2). Multisystem proteinopathy is a complex phenotype that includes FTD, Paget disease of the bone, inclusion body myopathy and MND, and can be due to mutations in VCP(valosing containing protein) and other recently identified genes.

scholarly journals Monogenic Causes of Strokes

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1855
Author(s):  
Justyna Chojdak-Łukasiewicz ◽  
Edyta Dziadkowiak ◽  
Sławomir Budrewicz
Keyword(s):  
Autosomal Recessive ◽  
Genetic Factors ◽  
Autosomal Dominant ◽  
Small Vessel Disease ◽  
Clinical Phenotype ◽  
Single Gene ◽  
Monogenic Disorders ◽  
Single Gene Disorders ◽  
Appropriate Therapy

Strokes are the main cause of death and long-term disability worldwide. A stroke is a heterogeneous multi-factorial condition, caused by a combination of environmental and genetic factors. Monogenic disorders account for about 1% to 5% of all stroke cases. The most common single-gene diseases connected with strokes are cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) Fabry disease, mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS) and a lot of single-gene diseases associated particularly with cerebral small-vessel disease, such as COL4A1 syndrome, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), and Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). In this article the clinical phenotype for the most important single-gene disorders associated with strokes are presented. The monogenic causes of a stroke are rare, but early diagnosis is important in order to provide appropriate therapy when available.

An Exploratory Retrospective Evaluation of Ropinirole-Associated Psychotic Symptoms in an Outpatient Population Treated for Restless Legs Syndrome or Parkinson's Disease

2009 ◽  
Vol 43 (9) ◽  
pp. 1426-1432 ◽  
Author(s):  
Steven C Stoner ◽  
Megan M Dahmen ◽  
Mignon Makos ◽  
Jessica W Lea ◽  
Lora J Carver ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine Receptors ◽  
Restless Legs Syndrome ◽  
Dopamine Agonists ◽  
Dual Therapy ◽  
Psychotic Symptoms ◽  
Antipsychotic Treatment ◽  
Restless Legs ◽  
Psychotic Features

Background: Traditional treatment approaches for the management of restless legs syndrome (RLS) and Parkinson's disease (PD) include the use of medications that either directly or indirectly increase dopamine levels. In turn, a potential adverse event that could be expected is the development or exacerbation of psychiatric-related symptoms. Objective: To evaluate and describe the incidence of psychosis and associated behavioral features in patients taking ropinirole for RLS or PD. Methods: Patients were identified from a computerized database search of outpatients being treated with ropinirole for 1 of 2 medical conditions: PD or RLS. Data were collected in a retrospective manner from 95 patients who were tracked over the course of their therapy to determine whether psychosis or associated behavioral symptoms developed as a result and whether an intervention was needed to adjust ropinirole dosing or if additional medications had to be added to control features associated with psychosis. Results: A total of 284 patients being treated for RLS or PD were identified; of this group, 95 patients were identified as being treated for PD or RLS with ropinirole. Of the 95 patients being treated with ropinirole, 13 developed psychotic features that required therapeutic intervention with either the use of an antipsychotic or dose adjustment of ropinirole. PD patients included in this study were numerically more likely to develop psychotic features compared with RLS patients; however, the difference was not statistically significant (p = 0.122). The results do suggest that this risk is increased when ropinirole is used as part of a dual therapy approach with dopamine agonists in the treatment of either PD or RLS (p = 0.003). Discussion: Dopamine agonists have long been used as preferred treatment in the management of PD and RLS. When treating either PD or RLS in the psychiatric population, the concern arises that increased activity at dopamine receptors may induce or exacerbate psychiatric features. A potential clinical concern with the use of ropinirole is the potential for patients to develop psychiatric features, although there are few data available to demonstrate whether stimulation of targeted individual dopamine receptors is linked to the development or exacerbation of psychotic features. It is also undetermined whether concurrent antipsychotic treatment provides any protective benefit against psychosis, especially in patients already being treated for psychotic symptoms. Conclusions: Our findings suggest that ropinirole may play a role in inducing or exacerbating psychosis and its associated features, although a number of confounding variables prevent the determination of a clear association and suggest that further investigation is warranted in controlled clinical trials.

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