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Scientific Reports Feb 2024After severe brain injury, zolpidem is known to cause spectacular, often short-lived, restorations of brain functions in a small subgroup of patients. Previously, we...
After severe brain injury, zolpidem is known to cause spectacular, often short-lived, restorations of brain functions in a small subgroup of patients. Previously, we showed that these zolpidem-induced neurological recoveries can be paralleled by significant changes in functional connectivity throughout the brain. Deep brain stimulation (DBS) is a neurosurgical intervention known to modulate functional connectivity in a wide variety of neurological disorders. In this study, we used DBS to restore arousal and motivation in a zolpidem-responsive patient with severe brain injury and a concomitant disorder of diminished motivation, more than 10 years after surviving hypoxic ischemia. We found that DBS of the central thalamus, targeted at the centromedian-parafascicular complex, immediately restored arousal and was able to transition the patient from a state of deep sleep to full wakefulness. Moreover, DBS was associated with temporary restoration of communication and ability to walk and eat in an otherwise wheelchair-bound and mute patient. With the use of magnetoencephalography (MEG), we revealed that DBS was generally associated with a marked decrease in aberrantly high levels of functional connectivity throughout the brain, mimicking the effects of zolpidem. These results imply that 'pathological hyperconnectivity' after severe brain injury can be associated with reduced arousal and behavioral performance and that DBS is able to modulate connectivity towards a 'healthier baseline' with lower synchronization, and, can restore functional brain networks long after severe brain injury. The presence of hyperconnectivity after brain injury may be a possible future marker for a patient's responsiveness for restorative interventions, such as DBS, and suggests that lower degrees of overall brain synchronization may be conducive to cognition and behavioral responsiveness.
Topics: Humans; Deep Brain Stimulation; Zolpidem; Akinetic Mutism; Motivation; Thalamus; Arousal; Brain Injuries
PubMed: 38316863
DOI: 10.1038/s41598-024-52267-1 -
Cureus Jan 2024A 77-year-old woman exhibited a rapid progression of dementia and declining physical function and, over a period of about four months, reached a state of akinetic...
A 77-year-old woman exhibited a rapid progression of dementia and declining physical function and, over a period of about four months, reached a state of akinetic mutism. A final diagnosis of Creutzfeldt-Jakob disease (CJD) was made. A nasogastric tube was inserted into the stomach, and then it was confirmed on X-ray that the end of the tube was in the correct position. She was discharged to a nursing home, where she received home medical care after discharge. One month after the nasogastric tube insertion, Tumguide® was used to assist in replacing the tube at this home. In home care settings where an X-ray machine may not be available, Tumguide® may assist with nasogastric tube insertion.
PubMed: 38222985
DOI: 10.7759/cureus.52082 -
Cureus Dec 2023Background Sporadic Creutzfeldt-Jakob disease (CJD), the most common form of human prion disease, is the archetypal diagnosis in this category. However, the spectrum of...
Background Sporadic Creutzfeldt-Jakob disease (CJD), the most common form of human prion disease, is the archetypal diagnosis in this category. However, the spectrum of possible diagnoses is wide, encompassing various treatable conditions. A lack of standardized diagnostic criteria and a tendency to opt for brain biopsies and clinical autopsies can be limiting factors in reaching a conclusive diagnosis. Objective This study aims to retrospectively analyze clinical and investigative findings in patients referred to a specialized neurology clinic exhibiting rapidly progressive dementia. These patients were ultimately diagnosed with Probable sporadic Creutzfeldt-Jakob disease (CJD) based on the 2018 CDC criteria for sporadic CJD. Materials and Methods This study included cases of CJD diagnosed based on clinical, electrophysiological, and imaging parameters at a tertiary care hospital in India from 2016 to 2020. The diagnostic criteria proposed by the CDC (Centers for Disease Control and Prevention) were employed to categorize patients as definite, probable, or possible CJD cases. All patients underwent MRI (magnetic resonance imaging) imaging and EEG ( electroencephalography) recording, while diagnostic brain biopsies were not conducted due to a lack of consent from close relatives. Results This observational descriptive study comprised four patients diagnosed with Probable sporadic CJD (sCJD), all of whom were female. The patients exhibited an age range of 57 to 75 years at the onset of the disease, with a mean age of onset at 67.5 years. Unfortunately, all patients succumbed to the disease within 6 months of its onset. Rapidly progressive dementia was a common symptom in all cases. Additionally, patient one and patient four displayed myoclonus and dystonia, patient two exhibited myoclonus and akinetic mutism, and patient three had myoclonus, chorea, and ataxia. MR brain imaging, including T2 sequence, FLAIR sequence, and DWI/ADC mapping, was performed on all patients, revealing both cortical gray matter and deep gray matter (basal ganglia) T2/FLAIR hyperintensities with DWI restriction. A cortical ribboning pattern was observed in all cases. EEG results indicated generalized delta slow waves with triphasic complexes in three patients, while patient three alone displayed periodic sharp wave complexes at a frequency of 1 per 1 - 1.5 seconds. Conclusion MRI with DWI and ADC brain mapping emerges as the most valuable diagnostic tool for patients with clinical presentations suggesting sCJD. In this study, all patients displayed restricted diffusion, as confirmed by ADC mapping. Regrettably, the characteristic features of sCJD with restricted diffusion in the cortex, thalamus, and basal ganglia may often elude detection by radiologists outside specialized centers, resulting in diagnostic delays. Conversely, when basal ganglia or cortical signal abnormalities are detected in conjunction with parenchymal swelling, alternative diagnoses such as encephalitis or lymphoma should be considered, as parenchymal swelling is not a typical feature of sCJD as revealed by MRI.
PubMed: 38186537
DOI: 10.7759/cureus.50008 -
Brain & NeuroRehabilitation Nov 2023Delayed encephalopathy (DE) following acute carbon monoxide (CO) poisoning is characterized by a wide range of neurological symptoms, including akinetic mutism,...
Delayed encephalopathy (DE) following acute carbon monoxide (CO) poisoning is characterized by a wide range of neurological symptoms, including akinetic mutism, cognitive impairment, and gait disturbances. Herein, we reported the case of a 61-year-old patient with DE after acute CO poisoning, who displayed heterogeneous patterns of cortical and subcortical structural integrity on diffusion tensor imaging (DTI). Four distinct patterns of diffusion tensor metrics (fractional anisotropy [FA] and mean diffusivity [MD]) were observed in the patient compared to age-matched controls (a decrease in FA and an increase in MD, a decrease in FA only, an increase in MD only, and an increase in FA and MD). This study revealed heterogeneous patterns of cortical and subcortical damage associated with DE after CO poisoning, contributing to a deeper understanding of the diverse clinical symptoms observed in this patient.
PubMed: 38047103
DOI: 10.12786/bn.2023.16.e34 -
BMC Neurology Oct 2023Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and ultimately fatal neurodegenerative condition caused by prions. The clinical symptoms of CJD vary with its...
BACKGROUND
Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and ultimately fatal neurodegenerative condition caused by prions. The clinical symptoms of CJD vary with its subtype, and may include dementia, visual hallucinations, myoclonus, ataxia, (extra)pyramidal signs and akinetic mutism. In the early course of disease however, several clinical symptoms of CJD may mimic those of co-existing morbidities.
CASE PRESENTATION
We report a male in his 60s with a history of situs inversus totalis and Churg Strauss syndrome, who presented with speech fluency disturbances, neuropsychiatric symptoms and allodynia, a few months after becoming a widower. Initially presumed a bereavement disorder along with a flare-up of Churg Strauss, his symptoms gradually worsened with apraxia, myoclonic jerks and eventually, akinetic mutism. MRI revealed hyperintensities at the caudate nucleus and thalami, while the cerebrospinal fluid was positive for the 14-3-3 protein and the real-time quick test, making the diagnosis of CJD highly probable. This case illustrates the complexities that may arise in diagnosing CJD when pre-existing multimorbidity may cloud the clinical presentation. We also discuss the potential mechanisms underlying the co-occurrence of three rare conditions (situs inversus totalis, Churg Strauss syndrome, CJD) in one patient, taking into consideration the possibility of coincidence as well as common underlying factors.
CONCLUSIONS
The diagnosis of CJD may be easily missed when its clinical symptoms are obscured by those of pre-existing (rare) multimorbidity. This case highlights that when the multimorbidity has neurological manifestations, an extensive evaluation remains crucial to establish the diagnosis, minimize the risk of prion-transmission and provide appropriate guidance to patients and their caregivers.
Topics: Humans; Male; Creutzfeldt-Jakob Syndrome; Akinetic Mutism; Churg-Strauss Syndrome; Multimorbidity; Myoclonus; Situs Inversus
PubMed: 37784069
DOI: 10.1186/s12883-023-03401-5 -
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 -
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 -
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