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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 -
BMC Neurology Jul 2023Creutzfeldt-Jakob disease (CJD), is a deadly degenerative condition of the central nervous system marked by rapidly progressive dementia. Magnetic resonance imaging...
BACKGROUND
Creutzfeldt-Jakob disease (CJD), is a deadly degenerative condition of the central nervous system marked by rapidly progressive dementia. Magnetic resonance imaging (MRI) abnormalities in the cerebral cortex, basal ganglia, thalamus, and cerebellum could indicate severe acute diseases caused by a variety of factors. Although their MRI patterns may resemble those of CJD, clinical history, additional MRI findings, and laboratory testing are all necessary to provide a reliable difference. Here, we report a misdiagnosed case of probable VV1 subtype of sporadic CJD (sCJD) in which follow-up MRI supported the diagnosis.
CASE PRESENTATION
A 41-year-old male patient attended the Neuropsychiatry Department with rapidly progressive dementia, akinetic mutism, and difficulty walking and speaking. His problem began with forgetfulness, disorganized behavior, and disorganized speech 7 months earlier which progressed rapidly and was accompanied by aphasia, apraxia, agnosia, and akinetic mutism in the last 2 months. On neurologic examination, hypertonia, hyperreflexia, frontal ataxia, bradykinesia, gait apraxia, and aphasia were noted. Based on clinical features and rapid symptoms progression the likely diagnosis of CJD was suspected. MRI and electroencephalography (EEG) were advised. MRI revealed features of diffuse cortical injury of both cerebral hemispheres also involving bilateral corpus striatum with evidence of cerebral volume loss. EEG showed lateralized periodic theta slow waves on the right side. According to the CDC's diagnostic criteria for CJD, the diagnosis of probable sCJD was established. Supportive care and symptomatic treatment are provided for the patient. After a 1-month follow up the patient's condition deteriorated significantly. The time-lapse from the first reported symptom to death was about 13 months.
CONCLUSION
The need of addressing CJD in patients presenting with rapidly progressive dementia is highlighted in this case report. In the early stages of the disease, interpretation of MRI results might cause diagnostic difficulties; therefore, follow-up MRI is critical in obtaining the correct diagnosis.
Topics: Male; Humans; Adult; Creutzfeldt-Jakob Syndrome; Akinetic Mutism; Magnetic Resonance Imaging; Electroencephalography; Diagnostic Errors
PubMed: 37464286
DOI: 10.1186/s12883-023-03318-z -
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 -
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 -
The European Journal of Neuroscience Mar 2024The clinical assessment of patients with disorders of consciousness (DoC) relies on the observation of behavioural responses to standardised sensory stimulation....
The clinical assessment of patients with disorders of consciousness (DoC) relies on the observation of behavioural responses to standardised sensory stimulation. However, several medical comorbidities may directly impair the production of reproducible and appropriate responses, thus reducing the sensitivity of behaviour-based diagnoses. One such comorbidity is akinetic mutism (AM), a rare neurological syndrome characterised by the inability to initiate volitional motor responses, sometimes associated with clinical presentations that overlap with those of DoC. In this paper, we describe the case of a patient with large bilateral mesial frontal lesions, showing prolonged behavioural unresponsiveness and severe disorganisation of electroencephalographic (EEG) background, compatible with a vegetative state/unresponsive wakefulness syndrome (VS/UWS). By applying an unprecedented multimodal battery of advanced imaging and electrophysiology-based techniques (AIE) encompassing spontaneous EEG, evoked potentials, event-related potentials, transcranial magnetic stimulation combined with EEG and structural and functional MRI, we provide the following: (i) a demonstration of the preservation of consciousness despite unresponsiveness in the context of AM, (ii) a plausible neurophysiological explanation for behavioural unresponsiveness and its subsequent recovery during rehabilitation stay and (iii) novel insights into the relationships between DoC, AM and parkinsonism. The present case offers proof-of-principle evidence supporting the clinical utility of a multimodal hierarchical workflow that combines AIEs to detect covert signs of consciousness in unresponsive patients.
Topics: Humans; Akinetic Mutism; Unconsciousness; Consciousness; Electroencephalography; Electric Stimulation Therapy
PubMed: 37077023
DOI: 10.1111/ejn.15994 -
Journal of Neurosurgery Apr 2024The lateral aspect of the cerebellomesencephalic fissure frequently harbors vascular pathology and is a common surgical corridor used to access the pons tegmentum, as...
OBJECTIVE
The lateral aspect of the cerebellomesencephalic fissure frequently harbors vascular pathology and is a common surgical corridor used to access the pons tegmentum, as well as the cerebellum and its superior and middle peduncles. The quadrangular lobule of the cerebellum (QLC) represents an obstacle to reach these structures. The authors sought to analyze and compare exposure of the cerebellar interpeduncular region (CIPR) before and after QLC resection and provide a case series to evaluate its clinical applicability.
METHODS
Forty-two sides of human brainstems were prepared with Klingler's method and dissected. The exposure area before and after resection of the QLC was measured and statistically studied. A case series of 59 patients who underwent QLC resection for the treatment of CIPR lesions was presented and clinical outcomes were evaluated at 1-year follow-up.
RESULTS
The anteroposterior surgical corridor of the CIPR increased by 10.3 mm after resection of the QLC. The mean exposure areas were 42 mm2 before resection of the QLC and 159.6 mm2 after resection. In this series, ataxia, extrapyramidal syndrome, and akinetic mutism were found after surgery. However, all these cases resolved within 1 year of follow-up. Modified Rankin Scale score improved by 1 grade, on average.
CONCLUSIONS
QLC resection significantly increased the exposure area, mainly in the anteroposterior axis. This surgical strategy appears to be safe and may help the neurosurgeon when operating on the lateral aspect of the cerebellomesencephalic fissure.
Topics: Humans; Cerebellum; Neurosurgical Procedures; Brain Stem; Microsurgery; Craniotomy
PubMed: 38564813
DOI: 10.3171/2023.7.JNS222838 -
Neuropathology : Official Journal of... Feb 2024Methionine/valine (MV) 2 type of sporadic Creutzfeldt-Jakob (sCJD) is divided into three subtypes based on neuropathological criteria: MV2-kuru (MV2K), MV2-cortical...
Methionine/valine (MV) 2 type of sporadic Creutzfeldt-Jakob (sCJD) is divided into three subtypes based on neuropathological criteria: MV2-kuru (MV2K), MV2-cortical (MV2C), and MV2K + C, exhibiting the co-occurrence of these two pathological features. We report an autopsy case of MV2K + C subtype of sCJD. A 46-year-old Japanese man began to make mistakes at work. Two months later, he gradually developed gait instability. The initial neurological examination revealed limb ataxia and myoclonus. Diffusion-weighted images (DWI) showed a hyperintensity in the right frontal cortex, basal ganglia, and thalamus. Ten months after the onset of disease, he fell into akinetic mutism. He died at 47 years of age, 12 months after the initial presentation. Pathological investigation revealed microvacuolation and confluent vacuoles in the cerebral cortex. In the basal ganglia and thalamus, there was severe neuronal loss and gliosis with mild spongiform change. Kuru plaques were found within the cerebellum. Prion protein (PrP) immunostaining revealed synaptic, perivacuolar, perineuronal, and plaque-like deposits in the cerebral cortex. There were synaptic and plaque-like PrP deposits in the basal ganglia, thalamus, and granular cell layer of the cerebellum. In these areas, plaque-like deposits mainly consisted of small deposits, whereas plaque-like deposits in the cerebral cortex consisted both of coarse granular and small deposits. Analysis of the PrP gene showed no pathogenic mutations, and Western blot examination revealed a mixture of type 2 and intermediate-type PrP. The progressive cognitive decline and ataxia in addition to the hyperintensity in the basal ganglia and/or thalamus on DWI are the basis for clinical diagnosis of MV2. The severe gliosis in the basal ganglia and various morphologies of plaque-like deposits that differ by the region may be characteristic of MV2K + C. Detailed neuropathological examination together with Western blot analysis is important to collect more cases for elucidating the pathogenesis of MV2K + C.
PubMed: 38353038
DOI: 10.1111/neup.12964 -
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 -
Age and Ageing May 2024Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive neurodegenerative disease with public health implications. Mean age of onset is 68 years....
INTRODUCTION
Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive neurodegenerative disease with public health implications. Mean age of onset is 68 years. Age-specific incidence declines after 80 years. This may arise from under-ascertainment or other biological features of the disease. Accurate characterisation of late-onset sCJD is important for early diagnosis, avoiding unnecessary investigations and improving ascertainment for public health purposes.
OBJECTIVE
To phenotype the clinical features and investigation profile of sCJD in adults >80 years.
METHODS
We analysed all probable and definite sCJD cases identified by the UK National CJD Research & Surveillance Unit over a 10-year period (2011-2021). Individuals were grouped by age of onset. Clinical features and investigation profiles were compared.
RESULTS
10.3% (123/1196) had an age of onset over 80. Median survival was shorter (3.2 vs 4.3 months; P < 0.001). Pyramidal signs (48.3% vs 34.2%; P = 0.008) and akinetic mutism (55.1% vs 33.2%; P < 0.001) were more frequent. Psychiatric symptoms (26.3% vs 39.6%; P = 0.01) and cerebellar signs (65.4% vs 78.6%, P = 0.007) were less frequent. Cognitive impairment and myoclonus were highly prevalent regardless of age. Between age groups, the diagnostic sensitivity of cerebrospinal fluid real-time quaking-induced conversion (CSF RT-QuIC) (92.9% vs 91.9%, P = 0.74) was comparable, electroencephalography was superior (41.5% vs 25.4%; P = 0.006) and MRI was inferior (67.8% vs 91.4%; P < 0.001).
CONCLUSIONS
Late-onset sCJD has distinct clinical features, shorter survival and a different profile of investigation sensitivity. CSF RT-QuIC, MRI brain and specialist CJD review is recommended in older adults with a rapidly progressive neurological disorder. Autopsy is valuable when the cause remains elusive.
Topics: Humans; Creutzfeldt-Jakob Syndrome; United Kingdom; Male; Female; Aged, 80 and over; Age of Onset; Incidence; Phenotype; Magnetic Resonance Imaging; Electroencephalography
PubMed: 38706391
DOI: 10.1093/ageing/afae086 -
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