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World Journal of Clinical Cases Sep 2023Prion diseases are a group of degenerative nerve diseases that are caused by infectious prion proteins or gene mutations. In humans, prion diseases result from mutations...
BACKGROUND
Prion diseases are a group of degenerative nerve diseases that are caused by infectious prion proteins or gene mutations. In humans, prion diseases result from mutations in the prion protein gene (PRNP). Only a limited number of cases involving a specific PRNP mutation at codon 196 (E196A) have been reported. The coexistence of Korsakoff syndrome in patients with Creutzfeldt-Jakob disease (CJD) caused by E196A mutation has not been documented in the existing literature.
CASE SUMMARY
A 61-year-old Chinese man initially presented with Korsakoff syndrome, followed by rapid-onset dementia, visual hallucinations, akinetic mutism, myoclonus, and hyperthermia. The patient had no significant personal or familial medical history. Magnetic resonance imaging of the brain revealed extensive hyperintense signals in the cortex, while positron emission tomography/computed tomography showed a diffuse reduction in cerebral cortex metabolism. Routine biochemical and microorganism testing of the cerebrospinal fluid (CSF) yielded normal results. Tests for thyroid function, human immunodeficiency virus, syphilis, vitamin B1 and B12 levels, and autoimmune rheumatic disorders were normal. Blood and CSF tests for autoimmune encephalitis and autoantibody-associated paraneoplastic syndrome yielded negative results. A test for 14-3-3 protein in the CSF yielded negative results. Whole-genome sequencing revealed a disease-causing mutation in PRNP. The patient succumbed to the illness 11 months after the initial symptom onset.
CONCLUSION
Korsakoff syndrome, typically associated with alcohol intoxication, also manifests in CJD patients. Individuals with CJD along with PRNP E196A mutation may present with Korsakoff syndrome.
PubMed: 37727484
DOI: 10.12998/wjcc.v11.i25.5982 -
JCPP Advances Sep 2023Selective mutism (SM) is an anxiety disorder that often starts in early years with serious and lasting consequences. Nonpharmacological interventions are commonly seen...
BACKGROUND
Selective mutism (SM) is an anxiety disorder that often starts in early years with serious and lasting consequences. Nonpharmacological interventions are commonly seen as the preferred first treatment. This systematic review identifies outcome measures used and outcomes achieved for nonpharmacological interventions for children and adolescents with SM.
METHODS
Systematic searches were conducted using 13 electronic databases and hand searches, including peer-reviewed and grey literature since 1992.
RESULTS
Twenty-five studies were identified. While specific measures varied, all studies reported an outcome measure for speaking behaviour and 18 used a measure of anxiety. Few studies reported measures of SM remission ( = 6), well-being ( = 6), academic impact ( = 2), or quality of life ( = 1). Within subject outcomes for nonpharmacological interventions were variable for improvements in speaking behaviours (very small to large positive effects) and reduction in anxiety symptoms (very small negative to large positive effects). Only five randomised controlled trials (RCTs) were included in the meta-analysis. Three studies compared a combined systems/behavioural approach with waitlist controls indicating a significant and large effect (Hedges = 1.06, < .0001, 95% CI: 0.57-1.56) on improved speaking behaviour. Two of these RCTs showed a large effect for SM remission favouring the intervention (Risk Ratio = 4.25, = .1774, 95% CI: 0.52-34.84) but this did not reach statistical significance. Non-significant outcomes for two RCTs with active controls (Hedges = 0.55, < .2885, 95% CI: -0.47 to 1.57) showed considerable heterogeneity in approach and outcomes, one with large and one with negligible effects.
CONCLUSION
Despite the considerable impairment caused by SM, there has been little systematic evaluation of non-pharmacological interventions. Although combined systems/behavioural interventions are promising, further systematic evaluations are urgently needed to inform treatment approaches. Cross-study measurement harmonisation is required to promote learning from all studies, including wider clinical and economic outcomes.
CLINICAL TRIAL REGISTRATION
Not applicable.
PubMed: 37720585
DOI: 10.1002/jcv2.12166 -
International Journal of Molecular... Aug 2023The co-occurrence of multiple proteinopathies is being increasingly recognized in neurodegenerative disorders and poses a challenge in differential diagnosis and patient...
Metabolic Brain Changes Can Predict the Underlying Pathology in Neurodegenerative Brain Disorders: A Case Report of Sporadic Creutzfeldt-Jakob Disease with Concomitant Parkinson's Disease.
The co-occurrence of multiple proteinopathies is being increasingly recognized in neurodegenerative disorders and poses a challenge in differential diagnosis and patient selection for clinical trials. Changes in brain metabolism captured by positron emission tomography (PET) with F-fluorodeoxyglucose (FDG) allow us to differentiate between different neurodegenerative disorders either by visual exploration or by studying disease-specific metabolic networks in individual patients. However, the impact of multiple proteinopathies on brain metabolism and metabolic networks remains unknown due to the absence of pathological studies. In this case study, we present a 67-year-old patient with rapidly progressing dementia clinically diagnosed with probable sporadic Creutzfeldt-Jakob disease (sCJD). However, in addition to the expected pronounced cortical and subcortical hypometabolism characteristic of sCJD, the brain FDG PET revealed an intriguing finding of unexpected relative hypermetabolism in the bilateral putamina, raising suspicions of coexisting Parkinson's disease (PD). Additional investigation of disease-specific metabolic brain networks revealed elevated expression of both CJD-related pattern (CJDRP) and PD-related pattern (PDRP) networks. The patient eventually developed akinetic mutism and passed away seven weeks after symptom onset. Neuropathological examination confirmed neuropathological changes consistent with sCJD and the presence of Lewy bodies confirming PD pathology. Additionally, hyperphosphorylated tau and TDP-43 pathology were observed, a combination of four proteinopathies that had not been previously reported. Overall, this case provides valuable insights into the complex interplay of neurodegenerative pathologies and their impact on metabolic brain changes, emphasizing the role of metabolic brain imaging in evaluating potential presence of multiple proteinopathies.
Topics: Humans; Aged; Creutzfeldt-Jakob Syndrome; Fluorodeoxyglucose F18; Parkinson Disease; Brain; Neurodegenerative Diseases
PubMed: 37685887
DOI: 10.3390/ijms241713081 -
Child's Nervous System : ChNS :... Jan 2024Posterior fossa tumour surgery in children entails a high risk for severe speech and language impairments, but few studies have investigated the effect of the tumour on...
PURPOSE
Posterior fossa tumour surgery in children entails a high risk for severe speech and language impairments, but few studies have investigated the effect of the tumour on language prior to surgery. The current crosslinguistic study addresses this gap. We investigated the prevalence of preoperative word-finding difficulties, examined associations with medical and demographic characteristics, and analysed lexical errors.
METHODS
We included 148 children aged 5-17 years with a posterior fossa tumour. Word-finding ability was assessed by means of a picture-naming test, Wordrace, and difficulties in accuracy and speed were identified by cut-off values. A norm-based subanalysis evaluated performance in a Swedish subsample. We compared the demographic and medical characteristics of children with slow, inaccurate, or combined slow and inaccurate word finding to the characteristics of children without word-finding difficulties and conducted a lexical error analysis.
RESULTS
Thirty-seven percent (n = 55) presented with slow word finding, 24% (n = 35) with inaccurate word finding, and 16% (n = 23) with both slow and inaccurate word finding. Children with posterior fossa tumours were twice as slow as children in the norming sample. Right-hemisphere and brainstem location posed a higher risk for preoperative word-finding difficulties, relative to left-hemisphere location, and difficulties were more prevalent in boys than in girls. The most frequent errors were lack of response and semantically related sideordinated words.
CONCLUSION
Word-finding difficulties are frequent in children with posterior fossa tumours, especially in boys and in children with right-hemisphere and brainstem tumours. Errors resemble those observed in typical development and children with word-finding difficulties.
Topics: Child; Male; Female; Humans; Cross-Sectional Studies; Infratentorial Neoplasms; Language; Brain Neoplasms
PubMed: 37682305
DOI: 10.1007/s00381-023-06119-4 -
Cureus Aug 2023Catatonia is a behavioral syndrome characterized by a variety of symptoms such as mutism, stupor, rigidity, negativism, and verbigeration. It can be caused by various...
Catatonia is a behavioral syndrome characterized by a variety of symptoms such as mutism, stupor, rigidity, negativism, and verbigeration. It can be caused by various psychiatric and general medical conditions. While the diagnosis in the pediatric population is relatively uncommon, emerging literature supports a higher prevalence of catatonia in children. We present a 12-year-old girl with a complex medical and psychosocial history, including a functional neurological disorder and concerns for child abuse and Munchausen syndrome by proxy imposed by her mother. The patient was initially admitted for medical management of vomiting and refusal to eat. Child psychiatry was consulted for further assessment and noted multiple catatonic symptoms with a Busch-Francis catatonia rating scale (BFCRS) score of 22. A subsequent 1 mg IV lorazepam challenge test showed improvement in the patient's symptoms with a repeat BFCRS score of 10. This case supports emerging literature suggesting a higher prevalence of catatonia in children and the importance of recognizing this syndrome and its wide array of underlying causes.
PubMed: 37680395
DOI: 10.7759/cureus.43082 -
Research Square Aug 2023Studies exploring the brain correlates of behavioural symptoms in the frontotemporal dementia spectrum (FTD) have mainly searched for linear correlations with single...
BACKGROUND
Studies exploring the brain correlates of behavioural symptoms in the frontotemporal dementia spectrum (FTD) have mainly searched for linear correlations with single modality neuroimaging data, either structural magnetic resonance imaging (MRI) or fluoro-deoxy-D-glucose positron emission tomography (FDG-PET). We aimed at studying the two imaging modalities in combination to identify nonlinear co-occurring patterns of atrophy and hypometabolism related to behavioural symptoms.
METHODS
We analysed data from 93 FTD patients who underwent T1-weighted MRI, FDG-PET imaging, and neuropsychological assessment including the Neuropsychiatric Inventory, Frontal Systems Behaviour Scale, and Neurobehavioral Rating Scale. We used a data-driven approach to identify the principal components underlying behavioural variability, then related the identified components to brain variability using a newly developed method fusing maps of grey matter volume and FDG metabolism.
RESULTS
A component representing apathy, executive dysfunction, and emotional withdrawal was associated with atrophy in bilateral anterior insula and putamen, and with hypometabolism in the right prefrontal cortex. Another component representing the disinhibition versus depression/mutism continuum was associated with atrophy in the right striatum and ventromedial prefrontal cortex for disinhibition, and hypometabolism in the left fronto-opercular region and sensorimotor cortices for depression/mutism. A component representing psychosis was associated with hypometabolism in the prefrontal cortex and hypermetabolism in auditory and visual cortices.
DISCUSSION
Behavioural symptoms in FTD are associated with atrophy and altered metabolism of specific brain regions, especially located in the frontal lobes, in a hierarchical way: apathy and disinhibition are mostly associated with grey matter atrophy, whereas psychotic symptoms are mostly associated with hyper-/hypo-metabolism.
PubMed: 37674710
DOI: 10.21203/rs.3.rs-3271530/v1 -
Cureus Aug 2023A 55-year-old African American man who was found down by a friend nine hours after being last seen at the same place was brought to the emergency department (ED) with...
A 55-year-old African American man who was found down by a friend nine hours after being last seen at the same place was brought to the emergency department (ED) with encephalopathy, lactic acidosis, rhabdomyolysis, elevated troponin, acute kidney injury (AKI), and transaminitis. His urine drug screen (UDS) was positive for cocaine. Intravenous (IV) Narcan was given with minimal improvement in mental status. A computed tomography (CT) scan of the head and a CT scan of the cervical spine in the ED showed no acute findings. Due to hypoxia, the patient was eventually intubated. The patient also required a fasciotomy and eventually hyperbaric oxygen (HBO) therapy due to the left lower extremity wound. He was transferred to our facility for further care. Due to incomplete cognitive recovery, as the patient was oriented to self only, further neurological workup, including magnetic resonance imaging (MRI) of the brain, was obtained, which showed bilateral symmetric T2 FLAIR (Fluid attenuated inversion recovery) hyperintensity in the globus pallidus. The patient had slow and gradual deterioration with worsening encephalopathy, akinetic mutism, parkinsonian features, and seizures, which prompted further evaluation from neurology. The patient eventually underwent extensive workup, including a continuous video electroencephalogram (cvEEG), repeat MRI brain with and without contrast, lumbar puncture for cerebrospinal fluid (CSF) analysis, MRI brain with diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS). The patient was treated with multivitamin therapy and coenzyme Q10, but there was no significant benefit. We report a case of cocaine-induced leukoencephalopathy with findings like 'chasing the dragon encephalopathy' with a possible component of delayed post-hypoxic injury with underlying neuroinflammation.
PubMed: 37667711
DOI: 10.7759/cureus.42966 -
Frontiers in Neurology 2023Creutzfeldt-Jakob Disease (CJD) is a rare, rapidly progressive, and fatal neurodegenerative disorder. We describe a man whose initial manifestations of CJD occurred...
Creutzfeldt-Jakob Disease (CJD) is a rare, rapidly progressive, and fatal neurodegenerative disorder. We describe a man whose initial manifestations of CJD occurred shortly after contracting Coronavirus disease 2019 (COVID-19). He first developed anxiety and short-term memory loss a few weeks after a mild COVID-19 infection. He subsequently developed parkinsonism, eventually progressed to akinetic mutism, and passed away 5 months after symptom onset. This case highlights a potential temporal relationship between COVID-19 infection and the onset of neurodegenerative symptoms. Microglia and astrocytes in the central nervous system (CNS) and 'S1' spike proteins on SARS-CoV-2 are potential mediators in neuroinflammation and neurodegeneration.
PubMed: 37609652
DOI: 10.3389/fneur.2023.1239576 -
Journal of Neurosurgery. Case Lessons Aug 2023The supplementary motor area (SMA) is essential in facilitating the commencement and coordination of complex self-initiated movements. Its complex functional...
BACKGROUND
The supplementary motor area (SMA) is essential in facilitating the commencement and coordination of complex self-initiated movements. Its complex functional connectivity poses a great risk for postoperative neurological deterioration. SMA syndrome can occur after tumor resection and comprises hemiakinesia and akinetic mutism (often, but unpredictably temporary). Although awake surgery is preferred for mapping and monitoring eloquent areas, connectomics is emerging as a novel technique to tailor neurosurgical approaches and predict functional prognosis, as illustrated in this case.
OBSERVATIONS
The authors report on a patient presenting with recurrent oligodendroglioma after subtotal resection 7 years earlier. After extensive neuropsychological and neuroradiological assessment (including connectomics), awake surgery was indicated. No intraoperative deficits were recorded; however, the patient presented with postoperative right-sided akinesia and mutism. Postoperative neuroimaging demonstrated the connectome overlapping the preoperative one, and indeed, neurological symptoms resolved after 3 days.
LESSONS
Comparison of the pre- and postoperative connectome can be used to objectively evaluate surgical outcomes and assess patient prognosis. To the best of the authors' knowledge, this is the first case demonstrating the feasibility of quantitative functional connectivity analysis as a prognostic tool for neurological improvement after surgery. A better understanding of brain networks is instrumental for improving diagnosis, prognosis, and treatment of neuro-oncological patients.
PubMed: 37581598
DOI: 10.3171/CASE23286 -
Frontiers in Neurology 2023Obsessive-compulsive disorder (OCD) is a common reason for patients to seek symptomatic treatment in psychiatric departments, which makes it challenging to consider...
BACKGROUND
Obsessive-compulsive disorder (OCD) is a common reason for patients to seek symptomatic treatment in psychiatric departments, which makes it challenging to consider underlying organic nervous system diseases. However, Creutzfeldt-Jakob disease (CJD) can present with atypical symptoms, sometimes even as initial symptoms, leading to misdiagnosis or missed diagnosis. Lumbar puncture and brain DWI are important diagnostic methods for CJD, and the detection of 1,433 protein can be performed to confirm the diagnosis.
CASE PRESENTATION
We present the case of a 63-year-old woman who was initially diagnosed with obsessive-compulsive disorder in 2022. Despite seven months of symptomatic treatment, her symptoms did not improve. She also developed symptoms of altered consciousness, such as upper limb tremors and mutism. Based on brain DWI and positive results from the detection of 1,433 protein, she was ultimately diagnosed with CJD.
CONCLUSION
Creutzfeldt-Jakob disease (CJD) can manifest initially as obsessive-compulsive disorder (OCD) with atypical symptoms, making it prone to misdiagnosis. Therefore, it is crucial to conduct further investigations, including lumbar puncture and imaging, to exclude organic nervous system diseases before initiating symptomatic treatment for psychiatric disorders. This approach can facilitate early diagnosis of CJD and other potential organic neurological diseases.
PubMed: 37533465
DOI: 10.3389/fneur.2023.1227566