Summary: This case report details a patient initially presenting with typical facio-brachial dystonic seizures, characteristic of anti-LGI1 encephalitis. However, the patient experienced rapid cognitive decline, myoclonus, and ultimately death, with neuroimaging showing hyperintensities and EEG revealing diffuse slowing with periodic sharp wave complexes, leading to a probable CJD diagnosis. The paper highlights the significant clinical overlap and diagnostic dilemmas between autoimmune encephalitis and CJD, noting that this specific presentation, where autoimmune encephalitis mimics CJD and progresses despite immunomodulatory therapy, is rarely described.

Summary: This study investigated the clinical overlap between sporadic Creutzfeldt-Jakob disease (sCJD) and dementia with Lewy bodies (DLB), noting that 46% of sCJD subjects met probable DLB criteria and 40% of DLB subjects met probable CJD criteria. Key differentiating symptoms included cerebellar signs, myoclonus, and visual symptoms (other than hallucinations) being more common in sCJD, while hallucinations and fluctuations were more prevalent in DLB. Magnetic resonance imaging (MRI) diffusion-weighted imaging hyperintensities were found in 96% of sCJD subjects but none with DLB, indicating MRI's utility in differentiation. EEG and CSF analyses showed limited sensitivity for sCJD in this study.

Summary: This retrospective study compared Creutzfeldt-Jakob disease (CJD) and voltage-gated potassium channel complex-associated autoimmune encephalitis (VGKC AE) in patients with rapidly progressive dementia, focusing on differentiating features. The study found that VGKC AE patients were more likely to have seizures and lower serum sodium levels, while CSF analysis showed higher white blood cell counts in VGKC AE and more frequent detection of CSF 14-3-3 protein and higher tau levels in CJD. Neuroimaging revealed diffusion restriction in the cortex, caudate, and putamen was more frequent in CJD. Initial and serial EEGs showed periodic sharp wave complexes and generalized suppressed activity were more common in CJD. The findings suggest that EEG, especially serial EEGs, can aid in distinguishing these two conditions.

Summary: This study presents seven patients with symptoms suggestive of "possible" Creutzfeldt-Jakob disease (CJD) who were diagnosed with Hashimoto's encephalitis. All patients had Hashimoto's thyroiditis with positive antibodies and/or hypoechoic thyroid ultrasonograms. CSF analysis showed increased leukocytes in three and elevated albumin in four, but the 14-3-3 protein and periodic sharp wave complexes typical of CJD were absent. Unlike CJD, which is fatal within months, Hashimoto's encephalitis patients often recovered quickly with corticosteroid treatment, highlighting that despite similar initial symptoms like dementia and myoclonus, the diseases have distinct diagnostic markers and prognoses.

Summary: This paper discusses autoimmune dementia and encephalopathy, emphasizing their importance in cases of subacute onset and rapidly progressive dementia, and highlights the need to distinguish them from neurodegenerative dementias due to their potential reversibility. It points to clinical features like facio-brachial dystonic seizures in anti-LGI1 encephalitis as diagnostic clues that can mimic myoclonus. The abstract also details diagnostic approaches including cognitive assessment, MRI, CSF analysis for inflammation, and neural autoantibody testing in serum and CSF to confirm the diagnosis and guide cancer searches, while cautioning against broad screening in elderly patients with insidious dementia and noting pitfalls in antibody testing. Treatment strategies involving acute and maintenance immunotherapy are mentioned, with prognosis potentially linked to antibody targets (cell-surface/synaptic vs. intracellular). The paper also notes emerging contexts for autoimmune dementias, such as post-herpes virus encephalitis and following immune-checkpoint inhibitor use.

Summary: This study analyzed patients with suspected Creutzfeldt-Jakob disease (CJD) who underwent autopsy, identifying 22 cases (11% of non-CJD diagnoses) with pathologically confirmed autoimmune encephalitis. These patients presented with common symptoms like dementia (90%), gait disturbance (86%), and neuropsychiatric symptoms (67%), and some had antineuronal antibodies detected in postmortem CSF, including against LGI1 and Caspr2. The findings highlight the importance of considering immune-mediated disorders in the differential diagnosis of rapidly progressive neurological deficits, especially when CJD is suspected.

Summary: This paper presents an atypical case of sporadic Creutzfeldt-Jakob disease (sCJD) in a patient who died within 5 weeks of symptom onset, highlighting the diagnostic challenges posed by its rarity and non-specific features. The patient exhibited a 2-week history of sudden cognitive decline, memory loss, aphasia, and ataxia, with MRI showing cortical ribboning and CSF positive for protein 14-3-3. Postmortem autopsy confirmed sCJD. The case emphasizes the importance of considering sCJD in rapidly progressive dementia and the utility of diagnostic tools like EEG, MRI, and CSF studies in confirming the diagnosis and excluding other conditions.

Summary: This study investigated brain MRI abnormalities, specifically DWI and FLAIR, in 107 patients with prion disease (CJD) and 40 non-prion related RPD patients. The methods involved a semiquantitative rating score for 22 brain regions, alongside clinical, CSF, and EEG data. Results showed that while most CJD patients had CJD-related cortical and thalamic changes, 2/107 had normal DWI-MRI. In non-prion RPD patients, DWI alterations showed distinct patterns, some suggestive of alternative diagnoses or CJD, aiding differentiation. The study concludes that negative/doubtful DWI makes CJD unlikely, and specific DWI patterns help distinguish CJD from other RPD causes, noting the pulvinar sign is not exclusive to variant CJD.

Summary: This study investigated the presence of neuronal surface antibodies (NSA-abs) in patients with suspected or definite Creutzfeldt-Jakob disease (CJD). In a cohort of 346 patients with suspected CJD, 1.7% tested positive for NSA-abs (including LGI1, CASPR2, NMDAR, aquaporin 4, Tr, and an unknown protein), and these patients showed improvement with treatment, with none meeting probable or possible CJD criteria. In contrast, none of the 49 patients with definite CJD had NSA-abs. The findings highlight the clinical utility of testing for NSA-abs in rapidly progressive neurological syndromes, particularly when CJD criteria are not definitively met, to identify potentially treatable autoimmune causes.

Summary: This review examines the clinical and pathophysiological links between autoimmune encephalitis and neurodegenerative disorders, highlighting shared symptoms like cognitive impairment and movement disorders, which often make autoimmune encephalitis a key differential diagnosis for rapidly progressive dementia. It addresses how chronic autoimmune presentations can be misdiagnosed as neurodegenerative diseases and discusses the presence of neuronal surface antibodies in established neurodegenerative conditions, exploring their potential roles. The paper also reviews long-term cognitive and neuroradiological changes in autoimmune encephalitis, predictive biomarkers, and specifically details IgLON5 antibody-related encephalitis as a model for antibody-neurodegeneration relationships.

Summary: This review discusses the clinical aspects and diagnostic workup for rapidly progressive dementia (RPD), a condition characterized by cognitive, behavioral, and motor decline within two years, with etiologies including neurodegenerative, inflammatory, infectious, and toxic-metabolic factors. It emphasizes Creutzfeldt-Jakob disease (CJD) as a primary concern and highlights the challenge of differentiating prion disease from reversible inflammatory processes that present similarly. The paper outlines a standardized approach for managing RPD patients, focusing on distinguishing CJD from other conditions with similar clinical and radiologic features.

Summary: This review discusses recent advancements in autoimmune encephalitis (AE), covering pathophysiology, genetics, diagnostic challenges, and clinical presentations associated with cell surface antibodies and anti-GAD. It highlights genetic associations (HLA) for antibodies like anti-LGI1 and anti-Caspr2, details cognitive and psychiatric symptoms in AE, and notes worse prognoses for late-onset anti-NMDARE and anti-GABA-B receptor encephalitis. The paper also expands on the clinical spectrum of various AE types, including new differential diagnoses, and reviews diagnostic criteria adaptations, potential mimics, assay limitations, treatment recommendations, and assessment scales.

Summary: This study evaluated the diagnostic accuracy of established electroencephalogram (EEG) criteria for periodic sharp-wave complexes (PSWCs) in diagnosing Creutzfeldt-Jakob disease (CJD). The criteria were applied to cases confirmed or excluded by autopsy, finding a sensitivity of 64% and specificity of 91% for CJD. The positive predictive value was 95% and negative predictive value was 49%. While 9% of non-CJD cases (specifically Alzheimer's disease and vascular dementia) were falsely positive, the authors conclude that these EEG criteria hold significant diagnostic value for CJD, especially when combined with clinical data.

Summary: This study evaluated the diagnostic utility of MRI, CSF, and EEG in differentiating sporadic Creutzfeldt-Jakob disease (sCJD) from other rapidly progressive dementias (npRPD) in a cohort of 30 patients. The findings indicate that sCJD patients exhibited cerebellar dysfunction, significantly higher CSF tau levels, positive CSF 14-3-3, and characteristic diffusion-weighted imaging (DWI) hyperintensities, which helped distinguish them from npRPD patients, although EEG findings were similar between the groups. Additionally, diffusion tensor imaging (DTI) revealed reduced diffusivity (MD, AD, RD) in the caudate and pulvinar of sCJD patients compared to controls and npRPD patients. The study concludes that CSF analysis and DWI MRI are valuable for distinguishing sCJD from npRPD.

Summary: This study retrospectively analyzed clinical records of 37 patients with rapidly progressive dementia (RPD) to assess the frequency of different etiologies and the accuracy of diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD). The findings indicated that non-prion diseases, both treatable (32%) and untreatable (38%), were more frequent than sCJD (30%), highlighting the critical need for rapid differential diagnosis. The evaluation of diagnostic tools showed DWI images had 73% sensitivity and 96% specificity, while FLAIR had low sensitivity (40%). CSF 14-3-3 protein demonstrated 100% sensitivity but low specificity (43%). CSF tau level emerged as the strongest independent predictor of sCJD, with 91% sensitivity and 83% specificity. The authors suggest that combining DWI images with CSF analysis of both 14-3-3 and total tau proteins offers the best diagnostic value for sCJD in RPD patients.

Summary: This case study describes a 75-year-old woman presenting with rapidly progressive cognitive impairment, initially diagnosed and treated for CASPR2 autoimmune encephalitis based on positive antineural antibodies. However, further symptoms and diagnostic results, including 14-3-3 proteins, suggested Creutzfeldt-Jakob disease (CJD), which was confirmed postmortem. The authors highlight the diagnostic challenges in differentiating CJD from treatable autoimmune encephalitis and emphasize the importance of aggressively seeking and treating potentially curable causes of dementia, while also cautioning about the risk of misdiagnosis from broad antibody screening.

Summary: This case report describes a 76-year-old man with VGKC-cAbs encephalitis who presented with periodic sharp wave complexes on EEG, a finding typically associated with Creutzfeldt-Jakob disease (CJD), thus complicating the differential diagnosis. The patient exhibited cognitive disturbance, generalized weakness, seizures, and severe encephalopathy, with MRI showing cerebellar and bifrontal cortical T2/FLAIR/DWI hypersignal. Despite immunotherapy, the patient died, and autopsy revealed mononuclear neocortex infiltrate without significant spongiosis. The study concludes that while cortical DWI hypersignal without restriction may help differentiate these conditions, the presence of PSWC in VGKC-cAbs encephalitis highlights the diagnostic challenges.

Summary: This paper presents three case reports of rapidly progressive dementia (RPD) with diverse etiologies, aiming to aid in differential diagnosis. Case 1 describes a 70-year-old woman with neuropsychiatric symptoms, inflammatory CSF, positive 14-3-3 protein, specific MRI findings in the caudate nuclei, and EEG showing periodic triphasic waves, suggestive of Creutzfeldt-Jakob disease. Case 2 details a 29-year-old man diagnosed with autoimmune encephalitis due to elevated antibodies against voltage-gated potassium channels, presenting with cognitive impairment and seizures. Case 3 involves a 49-year-old woman with encephalopathy, myoclonic seizures, and a positive NMDA-receptor antibody test, also indicative of autoimmune encephalitis. The authors emphasize the importance of early and accurate diagnosis for RPD patients, particularly for treatable or reversible conditions.

Summary: This review defines rapidly progressive dementias (RPDs) as a heterogeneous group of disorders including immune-mediated, infectious, metabolic encephalopathies, prion diseases, and atypical presentations of common neurodegenerative diseases. It highlights that some RPDs are treatable and require prompt diagnosis due to potential infectivity. The paper emphasizes the growing recognition of various encephalopathies, particularly those mediated by antibodies, as significant causes of rapid cognitive decline, alongside prion diseases which are considered prototypical RPDs. The review aims to equip clinicians with knowledge of RPD aetiologies, syndromes, and diagnostic work-up protocols to facilitate early and accurate diagnosis, thereby reducing morbidity and mortality, especially for immune-mediated and reversible dementias. It will cover diagnostic procedures, utility of biomarkers, and treatment options, including steroid therapy in ambiguous cases.

Summary: This paper discusses the clinical diagnosis and differential diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) and variant Creutzfeldt-Jakob disease (vCJD). It notes that sCJD, the most common form of transmissible spongiform encephalopathy, typically affects individuals in their sixties and presents with rapidly progressive dementia, focal neurological signs, and myoclonus. Diagnostic support for sCJD includes periodic sharp and slow wave complexes on EEG, basal ganglia hyperintensities on MRI, and elevated CSF neuronal proteins like 14-3-3, contrasting with the posterior thalamus hyperintensities (pulvinar sign) seen in vCJD. The paper also mentions that Alzheimer's disease and Lewy body dementia are common differential diagnoses for sCJD in elderly patients, while chronic inflammatory CNS disorders are considered in younger patients.

Summary: This study investigated patients diagnosed post-necropsy with Alzheimer's disease (AD) or dementia with Lewy bodies (DLB) who were initially suspected of having Creutzfeldt-Jakob disease (CJD). The research analyzed the clinical symptoms, signs, and diagnostic findings of these patients, comparing them to a group with confirmed CJD. Key findings indicate that rapid progression, focal neurological signs, myoclonus, and limb rigidity are common across AD, DLB, and CJD, and that periodic sharp wave complexes on EEG, typically associated with CJD, were present in some AD and DLB patients. Notably, DLB patients often presented with parkinsonism and fluctuations, yet were not suspected of DLB. The study concludes that while CJD should be the primary consideration in rapidly progressive dementia with focal signs, AD should be considered for slower courses, and DLB for presentations with parkinsonism or fluctuations, emphasizing that EEG or CSF findings typical of CJD do not exclude AD or DLB.

Summary: The paper reports a case of a 59-year-old woman diagnosed with probable Creutzfeldt-Jakob disease (CJD) based on clinical symptoms (blurred vision, dysarthria, myoclonus, rapidly progressive dementia), positive 14-3-3 protein in CSF, periodic sharp waves on EEG, and characteristic MRI findings. However, the patient also had high titers of antithyroid antibodies, suggesting features of Hashimoto's encephalopathy. Corticosteroid pulse therapy, a treatment for Hashimoto's encephalopathy, led to a symptomatic aggravation, including increased seizure activity and ballistic dyskinesia, which was managed with clonazepam. This case highlights the diagnostic challenge in differentiating CJD from Hashimoto's encephalopathy and demonstrates a negative effect of corticosteroid therapy in a patient with CJD who also presented with features of Hashimoto's encephalopathy, underscoring the need for careful consideration before initiating such treatment in uncertain diagnoses.

Summary: This study retrospectively reviewed four patients diagnosed with probable sporadic Creutzfeldt-Jakob disease (CJD), characterized by rapidly progressive dementia and myoclonus, with periodic sharp wave complexes (PSWC) on EEG in three patients. The study highlights that while the characteristic triad of symptoms usually appears late, CJD can present with atypical features initially. Diagnostic findings included high levels of 14-3-3 protein and tau protein, normal amyloid β1-42 in CSF, and specific MRI hyperintensities. The authors conclude that a combination of biomarkers is crucial for early diagnosis, especially given the difficulty of obtaining brain tissue confirmation.

Summary: This paper presents a case study of a woman in her 60s with a one-month history of rapidly progressive dementia, characterized by vertigo, cognitive decline, ataxia, and myoclonus. It highlights the challenges in evaluating such cases due to a broad differential diagnosis. The abstract notes that elevated cerebrospinal fluid total tau was instrumental in diagnosis and prognosis discussions. The paper aims to summarize a systematic diagnostic approach for patients with rapidly progressive dementia and review recent literature on biomarkers for Creutzfeldt-Jakob disease and autoimmune encephalitis.

Summary: This review updates on the neuroimaging patterns of sporadic Creutzfeldt-Jakob disease (sCJD), emphasizing magnetic resonance (MR) imaging, and discusses its clinical scenario, molecular basis, and correlations with genetic and imaging findings in prion disease subtypes. It aims to aid radiologists in identifying typical and atypical sCJD patterns by providing a comprehensive pictorial review of differential diagnoses, highlighting diffusion-weighted imaging (DWI) as pivotal for diagnosis and ruling out mimicking disorders.

Summary: This article explores various conditions that mimic sporadic Creutzfeldt-Jacob disease (CJD) in patients presenting with subacute encephalopathy, a scenario neurologists frequently encounter. It covers common neurodegenerative mimics as well as rarer, treatable conditions that should not be overlooked. The paper discusses essential investigations such as serum antibodies, CSF analysis, electroencephalography (EEG), and MR brain imaging, and outlines strategies for managing cases where initial investigations do not strongly support CJD but no clear alternative diagnosis is immediately apparent.

Summary: This study retrospectively analyzed five probable sporadic Creutzfeldt-Jakob Disease (sCJD) cases diagnosed between 2007-2017. The paper highlights typical sCJD neurological signs including rapidly progressive dementia and myoclonus, and characteristic EEG findings of periodic sharp wave complexes. MRI findings commonly included cerebral atrophy and ventricular enlargement, with specific signal intensity increases in the caudate nucleus, putamen, and cerebral cortex. Extensive differential diagnostic workups, including autoimmune panels and anti-neuronal antibody testing, were performed but did not reveal alternative diagnoses. All patients succumbed to the disease within months of symptom onset, underscoring sCJD's diagnostic challenge due to its rarity and broad differential diagnosis.

Summary: The paper presents two cases of pathologically confirmed dementia with Lewy bodies (DLB) where electroencephalogram (EEG) recordings showed periodic discharges that were suggestive or typical of Creutzfeldt-Jakob disease (CJD). These EEG findings led to diagnostic confusion and the implementation of prion disease precautions during postmortem examinations. The authors note that periodic sharp wave complexes have been reported in DLB and should not preclude a DLB diagnosis when other clinical and neuropsychological features are consistent with established criteria.

Summary: This paper presents a case study of a 76-year-old individual with a 6-month history of rapidly progressive dementia, characterized by cognitive impairment, aphasia, visual hallucinations, and ataxia. The initial differential diagnosis included Creutzfeldt-Jakob disease (CJD) versus autoimmune encephalitis. The patient's condition worsened, leading to akinetic mutism and myoclonus, and an autopsy confirmed sporadic CJD. The paper uses this case to discuss the clinical and diagnostic considerations for rapidly progressive dementia and elaborates on CJD and autoimmune encephalitis as the primary diagnostic possibilities.

Summary: The abstract describes two clinical forms of Hashimoto's encephalopathy: a vasculitic form with stroke-like episodes, seizures, and mild cognitive decline, and a diffuse form presenting with depression, psychosis, myoclonus, tremors, delusions, fluctuating consciousness, and dementia. It notes that clinical manifestations can be fluctuating or persistent and are reversible with immunosuppressive therapy.

Summary: This paper discusses a case of a 67-year-old male diagnosed with dementia with Lewy bodies (DLB) who initially presented with symptoms such as rapidly progressive deterioration, myoclonus, and gait disturbance, leading to suspicion of Creutzfeldt-Jakob disease (CJD) or another encephalopathy. The study aims to describe this clinically atypical presentation of probable DLB and review similar cases from the literature, proposing the existence of a rapidly progressive clinical subtype of DLB.

Summary: This paper discusses Creutzfeldt-Jakob disease (CJD), a prion disease characterized by abnormal prion protein accumulation and spongiform degeneration of the brain, noting its rarity and historical description. The study specifically focuses on the clinical findings of CJD when it mimics dementia with Lewy bodies.

Summary: This paper highlights the importance of recognizing faciobrachial dystonic seizures (FBDS) as a key indicator of anti-LGI1 autoimmune encephalitis, a condition that can mimic Creutzfeldt-Jakob Disease (CJD) in patients with rapidly progressive dementia (RPD). The authors report on two Brazilian patients with FBDS and confirmed anti-LGI1 encephalitis, who presented with limbic encephalitis features, hyponatremia, and normal CSF, responding well to immunotherapy. The study concludes that FBDS can be mistaken for myoclonus and occur alongside rapid cognitive decline, and failing to identify it can lead to misdiagnosing a treatable cause of RPD as CJD.

Summary: This paper reviews PubMed-listed research on the diagnosis and treatment of diseases causing rapid cognitive decline, including inflammatory diseases, rapidly progressive neurodegenerative diseases, toxic-metabolic encephalopathies, and prion diseases. It highlights the diagnostic challenges due to overlapping clinical presentations and emphasizes the importance of an extended diagnostic workup, including the search for neoplasia and atypical encephalitis, especially given the discovery of new immune-mediated disorders. The authors suggest considering high-dose steroid therapy in certain situations even without clear evidence of inflammation, drawing upon experience from Creutzfeldt-Jakob Disease surveillance activities.

Summary: This case report details a 51-year-old woman with a history of Hashimoto's thyroiditis who presented with rapidly progressive dementia, myoclonus, visual disturbances, and EEG findings characteristic of sporadic Creutzfeldt-Jakob disease (sCJD). Diagnostic tests confirmed sCJD, with elevated 14-3-3 protein and positive RT-QuIC, alongside elevated thyroid peroxidase antibodies. The authors suggest that CJD might modulate the immune system, potentially leading to a steroid non-responsive autoimmune encephalitis, and recommend evaluating patients with CJD for autoimmune encephalitis and monitoring TPO antibodies, considering steroids as adjuvant therapy.

Summary: The paper discusses the clinical diagnosis of Creutzfeldt-Jakob disease (CJD), highlighting reliance on patient history (rapidly progressive dementia), neurological findings (ataxia, myoclonus, akinetic mutism), and EEG patterns. It notes that CSF markers like 14-3-3 and neuron-specific enolase aid in diagnosing variant forms, though they can also be elevated in other conditions like encephalitis. The abstract also touches upon different subtypes of sporadic CJD and mentions that differential diagnosis includes treatable dementias such as herpes encephalitis, multiple sclerosis, and Hashimoto encephalitis, particularly in younger patients.

Summary: This paper reports a case of Hashimoto's encephalopathy (HE) that presented with unusual features, specifically positive 14-3-3 protein in the cerebrospinal fluid (CSF) and an atypical clinical course that mimicked Creutzfeldt-Jakob disease (CJD). It highlights that while CJD is characterized by rapidly progressive dementia, ataxia, and myoclonus, and 14-3-3 protein in CSF is a known marker for CJD, HE can share common clinical features with CJD and, in this case, presented with a marker typically associated with CJD, complicating the differential diagnosis.

Summary: This case report details a 59-year-old female who presented with rapid onset dementia characterized by frontal executive dysfunction, apathy, and cognitive decline. Despite initial treatments being ineffective, the patient was diagnosed with Hashimoto's encephalopathy (HE) based on elevated antithyroid antibodies. While corticosteroids were ineffective, treatment with plasmapheresis led to significant and stable clinical improvement, normalization of FDG-PET findings, and demonstrated that HE can mimic frontal dementia syndromes and be successfully treated with immunosuppressive therapy like plasmapheresis.

Summary: This article discusses autoimmune encephalitis (AE) as a critical differential diagnostic consideration for rapidly progressive dementia (RPD). It emphasizes the importance of identifying potential autoimmune causes for RPD by examining clinical history and examination findings. The paper highlights that while infectious and toxic-metabolic causes are commonly tested, early ancillary testing for AE is necessary in appropriate RPD cases, with autoantibody testing in serum and spinal fluid, brain imaging, and electroencephalography forming the initial investigative steps.

Summary: This paper presents an uncommon case of Creutzfeldt-Jakob disease (CJD) that initially manifested as primary progressive aphasia (PPA), leading to a misdiagnosis of frontotemporal dementia. The study highlights that focal periodic sharp wave complexes were detected on EEG eight months after symptom onset, which later evolved into diffuse abnormalities characteristic of CJD, supported by MRI findings. The patient eventually developed other typical CJD symptoms, including visual disturbances, ataxia, extrapyramidal signs, dysphagia, and mutism, succumbing to the disease 34 months after onset. The authors emphasize that PPA is a rare initial presentation of CJD (about 1% of cases) and underscore the importance of including brain MRI and wake/sleep EEG in the diagnostic workup for patients presenting with PPA.

Summary: This study aimed to establish clinical diagnostic markers for MM2-type sporadic Creutzfeldt-Jakob disease (sCJD), as pathological examination is currently the only definitive method. The research analyzed eight patients with confirmed MM2-type sCJD, classifying them into cortical, thalamic, and combined forms. The cortical form was associated with late-onset, slowly progressive dementia, cortical hyperintensity on DWI MRI, and elevated CSF 14-3-3 protein. The thalamic form presented with diverse neurological symptoms, longer disease duration, and typically absent characteristic EEG and MRI abnormalities, though thalamic hypoperfusion on SPECT was noted. The combined form showed features of both. The study concluded that cortical DWI hyperintensity is useful for the cortical form, while thalamic hypoperfusion or hypometabolism on SPECT/PET is indicative for the thalamic form.

Summary: This paper reports on four cases of Creutzfeldt-Jakob disease (CJD), a rare, rapidly progressive neurodegenerative disorder, observed over a two-year period. The cases highlight the varied clinical presentations of CJD, including cognitive decline, myoclonus, Parkinsonism, ataxia, and akinetic mutism, with rapid progression to death within weeks to months. The authors emphasize the importance of considering CJD in patients with atypical presentations of rapidly progressive cognitive decline and note that while brain biopsy is the gold standard, CSF protein 14-3-3, typical MRI findings, and suggestive EEG abnormalities support the diagnosis.

Summary: This paper discusses the diagnostic challenges of prion diseases like Creutzfeldt-Jakob disease (CJD) in cases of rapidly progressive dementia, noting that conditions such as Alzheimer's disease (AD) and Lewy Body Disease (LBD) are often misdiagnosed as CJD due to symptom overlap. It highlights the limitations of current diagnostic methods and emphasizes real-time quaking induced conversion (RT-QuIC) as a highly sensitive technique for early and accurate CJD diagnosis. The abstract also presents a case study of a patient with rapidly progressing dementia initially suspected of CJD, where advanced diagnostics including a brain biopsy ultimately confirmed sporadic CJD, underscoring the importance of sensitive methods like RT-QuIC.

Summary: The paper reports on a case of a 70-year-old man with rapidly progressive dementia (RPD) and psychiatric symptoms, initially suspected to be Creutzfeldt-Jakob disease (CJD) or autoimmune encephalitis, but testing was negative and treatment ineffective. Based on further tests, dementia with Lewy bodies (DLB) was suspected, but anti-Parkinsonian drugs were also unhelpful. An autopsy confirmed DLB with extensive Lewy bodies and significant amyloid deposition, but minimal neurofibrillary tangles. The authors highlight that while DLB is typically chronic, some cases present with RPD, making differentiation from CJD crucial, and suggest that amyloid deposition may play a role in the rapid progression observed in this case.

Summary: This review explores movement disorders in autoantibody-associated neurological diseases, highlighting their potential to mimic other conditions and their treatable nature. It details specific antibody-movement disorder associations, such as NMDAR antibodies with dyskinesias and LGI1 antibodies with paroxysmal dystonias, and outlines a syndromic approach based on clinical presentation and antibody profiles. The paper also delves into the underlying immunopathophysiology, treatment implications, and emerging parallels between genetic and immunological movement disorders, exemplified by glycine receptor antibodies mimicking hereditary hyperekplexia.

Summary: This paper presents a case report of a 70-year-old man diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD) based on the 2017 Euro-CJD criteria. sCJD is described as a rare, uniformly fatal neurodegenerative disorder causing rapidly progressive dementia, myoclonus, visual disturbances, cognitive decline, and neurological signs, though these symptoms are nonspecific. The abstract highlights the utility of diffusion-weighted MRI, specifically ribbon-like cortical hyperintensities, as a key diagnostic tool for sCJD. The presented case featured rapidly progressive anxiety and dementia, blurry vision, extrapyramidal signs, and MRI findings consistent with sCJD.

Summary: This study evaluated the diagnostic utility of a broad panel of neural antibodies in 10,919 patients with suspected autoimmune neuropsychiatric conditions. It found that antibodies against LGI1, CASPR2, NMDAR, AMPAR, and GABABR were frequently detected and associated with autoimmune diagnoses, with good interlaboratory agreement for LGI1 and CASPR2. The findings indicate that routine antibody diagnostics are reliable and have therapeutic implications, with 64% of patients with surface antibodies showing improvement after immunotherapy. The study also highlights the importance of CSF testing for certain antibodies like NMDAR, as serum testing alone may be insufficient.

Summary: This chapter explores the link between the immune system and neuropsychiatric disorders, focusing on autoimmune encephalitides caused by neuronal surface antibodies (NSAbs) like those targeting NMDA receptor and LGI1. It discusses autoimmune disorders with psychiatric comorbidities such as SLE and MS, and details the psychiatric presentations, treatments, and outcomes of various autoimmune encephalitides, highlighting the significance of NSAbs in psychiatry.

Summary: This paper discusses rapidly progressive dementias (RPDs), highlighting human prion diseases (PrDs) such as Creutzfeldt-Jakob disease (CJD) as a common cause. It notes that CJD presents with varied clinical features and can be sporadic, genetic, or acquired. The abstract emphasizes that diffusion-weighted brain MRI is the most sensitive diagnostic test for CJD, with CSF and EEG also aiding confirmation, and mentions the availability of a highly specific CSF test in some regions. Currently, CJD treatment is symptomatic, lacking disease-modifying therapies. The paper also points out that CJD is frequently confused with other RPDs and suggests the VITAMINS acronym as a tool for differential diagnosis, particularly for identifying treatable causes early.

Summary: This paper reviews the molecular and immunologic aspects of limbic encephalitis (LE), a rare condition causing acute or subacute neuropsychiatric symptoms like memory deficits, confusion, seizures, and movement disorders. LE is attributed to antibodies targeting neuronal antigens, leading to altered synaptic transmission, particularly in the limbic system. The abstract highlights that diagnosis relies on high clinical suspicion and neuronal antibody testing due to the lack of sensitive CSF markers and variable radiographic findings. It also notes the importance of identifying and treating concomitant tumors in paraneoplastic LE, alongside immunotherapy.

Summary: This systematic review examines sporadic Creutzfeldt-Jakob disease (sCJD), a rare, fatal neurodegenerative disorder characterized by a rapid clinical course. The paper notes an apparent rise in incidence, potentially due to improved diagnostic tools, and emphasizes the need for physician awareness due to the variable initial presentation. It highlights advancements in understanding sCJD's pathogenesis and the identification of reliable biomarkers, which have led to updated diagnostic criteria and potential therapeutic targets, though evaluating these strategies is challenging given the disease's low incidence and rapid progression.

Summary: This paper reviews the spectrum of atypical early manifestations of Creutzfeldt-Jakob disease (CJD) to improve early diagnosis, especially in light of new ultrasensitive assays like RT-QuIC. It highlights that CJD patients can present with isolated or atypical symptoms, such as sensory disturbances, seizures, psychiatric symptoms, parkinsonian syndromes, pseudobulbar syndrome, involuntary movements (including myoclonus), stroke-like presentations, aphasia, and neuropathy, which can challenge early clinical identification. The authors emphasize the need for awareness of these varied presentations to enhance diagnostic accuracy and patient selection for therapeutic trials.

Summary: This study reviewed 25 patients with sporadic Creutzfeldt-Jakob disease (sCJD) who presented with movement disorders. The median age at presentation was 58 years, with a median illness duration of 5 months. Myoclonus, ataxia, and parkinsonism were the most common movement disorders observed. Brain MRI showed basal ganglia abnormalities and cortical ribboning in over two-thirds of cases, while EEG revealed abnormalities, including triphasic waves and periodic sharp waves, in most patients. The study concluded that myoclonus, ataxia, and parkinsonism are frequent movement disorder phenotypes in sCJD, noting atypical presentations like ataxic, CBS-like, and choreiform presentations.

Summary: This review discusses recent advances in the diagnosis of Creutzfeldt-Jakob disease (CJD) and other prion diseases, highlighting the evolution from nonspecific clinical, EEG, and CSF markers to more sensitive techniques like MRI diffusion-weighted imaging (DWI) and real-time quaking-induced conversion (RT-QuIC) assays. These newer methods, incorporated into revised diagnostic criteria, significantly improve accuracy and enable earlier diagnosis. However, the paper notes that some prion disease subtypes remain challenging to diagnose, requiring a comprehensive approach including clinical presentation, neuroimaging, CSF analysis, EEG, and genetic testing, and emphasizes the need for standardization and surveillance for emerging prion diseases.

Summary: This case report details a misdiagnosed 41-year-old male with the VV1 subtype of sporadic Creutzfeldt-Jakob disease (sCJD), presenting with rapidly progressive dementia, akinetic mutism, and gait/speech difficulties. Initial MRI showed diffuse cortical injury and cerebral volume loss, while EEG revealed lateralized periodic theta slow waves, leading to a probable sCJD diagnosis. The report emphasizes that early MRI interpretation can be challenging, underscoring the critical role of follow-up MRI for accurate diagnosis in such cases.

Summary: This retrospective study analyzed 31 patients diagnosed with CJD between 2003-2010, all presenting with rapidly progressive dementia (mean duration 4.25 months), and noted various neurological findings including myoclonus in a subset. The study compared the diagnostic performance of UCSF, European MRI-CJD Consortium, and WHO criteria, finding significant variability, with the European criteria (including neuroimaging and CSF biomarkers) diagnosing more cases than WHO (CSF only) or UCSF (neuroimaging only) criteria. The paper highlights the diagnostic utility of neuroimaging, particularly cortical ribboning and basal ganglia hyperintensity, while also noting false positives. It also lists CJD mimics encountered, such as neurosarcoidosis and viral encephalitis.

Summary: This paper reports a case of a 59-year-old woman with cognitive impairment and language disturbances, whose brain MRI revealed cortical diffusion restriction suggestive of Creutzfeldt-Jakob disease (CJD). Despite the MRI findings, the patient lacked typical clinical features like myoclonus or characteristic periodic sharp wave complexes on EEG, and CSF 14-3-3 was negative, not meeting CJD diagnostic criteria at the time. However, a positive RT-QuIC assay on CSF and subsequent pathology confirmed sporadic CJD (subtype MM/MV 2C), demonstrating the utility of RT-QuIC in diagnosing CJD even with atypical presentations and the importance of considering CJD despite the absence of classic EEG markers.

Summary: This study investigated the correlation between clinical features, prion protein codon 129, and molecular subtype with MRI basal ganglia hyperintensity in 219 patients, including 153 confirmed sporadic Creutzfeldt-Jakob disease (CJD) cases. Patients with basal ganglia high signal on T2-weighted MRI were more likely to exhibit rapid progressive dementia early and had shorter disease durations. Conversely, patients without basal ganglia signal increase showed a higher frequency of extrapyramidal disturbances, depression, and sensory disturbances. The MRI was found to be more diagnostic in patients with the MV2 molecular subtype, indicating that selected clinical and pathological features correlate with basal ganglia high signal on T2-weighted MRI in CJD patients.

Summary: The paper presents a case of a 54-year-old woman with a 3-month history of subacute progressive cognitive decline, memory difficulties, impaired decision-making, myoclonus, and gait ataxia, leading to significant functional impairment. Her medical history includes celiac disease, collagenous colitis, Raynaud syndrome, osteopenia, anxiety, and prior hyponatremia. Neurological examination revealed encephalopathy, multifocal myoclonus, postural tremor, and ataxia.

Summary: This paper reports on two cases of Creutzfeldt-Jakob disease (CJD), one sporadic and one genetic, highlighting their clinical presentations and diagnostic findings. The sporadic case presented with dizziness and hypomnesis, initially suspected as viral encephalitis, but later showed characteristic findings on cranial MRI (lace sign), periodic synchronous discharge on EEG, and positive CSF 14-3-3 protein, leading to a diagnosis of sporadic CJD. The genetic case presented with progressive hypomnesis and was diagnosed with genetic CJD due to a V203I mutation in the PRNP gene, despite a negative CSF 14-3-3 protein test. Both patients died shortly after diagnosis. The authors emphasize the importance of early diagnosis for treatment, transmission prevention, and avoiding disputes.

Summary: This study explores the role of antibodies against neuronal surface antigens in central nervous system disorders, building on their discovery in encephalitis and potential for immunotherapy. The research examined antibody presence in patients with narcolepsy type 1, chronic neurological conditions (epilepsy, neurodegenerative disorders), and controls, finding higher antibody frequencies in CNS disorders without specific disease associations. An animal model was developed by injecting CASPR2 antibodies into mice with a transiently opened blood-brain barrier, which resulted in altered behavior (working memory, anxiety) and neuropathological changes including Purkinje cell loss, astrocytosis, and microglial/astrocyte activation, supporting a pathogenic role for CASPR2 antibodies and demonstrating the impact of antibodies accessing the brain via a brief blood-brain barrier opening.

Summary: This chapter outlines a clinical approach to evaluating dementia and cognitive decline beyond Alzheimer's disease, emphasizing traditional neurological methods like history and examination. It specifically addresses disorders with subacute onset (days to weeks) and uncommon conditions causing cognitive and neuropsychiatric disturbances, often linked to systemic illness, highlighting the importance of diagnosing treatable causes.

Summary: This paper reports the case of a 65-year-old male presenting with progressive dementia, typical neurologic symptoms, myoclonic jerks, and magnetic resonance imaging findings consistent with Creutzfeldt-Jakob disease (CJD). It emphasizes that while prion diseases are classic causes of rapidly progressive dementia (RPD), reversible conditions can mimic them and should be considered in the differential diagnosis, highlighting the importance of a high index of suspicion for diagnosing CJD.

Summary: This review focuses on laboratory diagnostic approaches for transmissible spongiform encephalopathies (TSEs), specifically Creutzfeldt-Jakob disease (CJD), by examining surrogate markers rather than direct PrPSc detection. It highlights that single markers like tau-protein, S-100B, and 14-3-3-protein have demonstrated high diagnostic certainty for CJD. The paper anticipates that combining these markers will further enhance diagnostic accuracy, particularly in the broader differential diagnosis of various dementias, including subtypes of CJD and Alzheimer's dementia.

Summary: This paper highlights that rapidly progressive dementias (RPDs) pose a diagnostic challenge due to their atypical presentation compared to slowly progressing dementias. It notes that while conditions like Alzheimer's disease and frontotemporal dementia typically develop slowly, they can occasionally present as RPDs, with dementia with Lewy bodies and corticobasal degeneration being more common exceptions that can manifest as RPDs.

Summary: This retrospective, observational study analyzed eight cases of suspected Creutzfeldt-Jakob disease (CJD) encountered between 2010-2013 in Bangalore, India. The patients, with a mean age of 66.6 years and female predominance, presented with cognitive disturbance (100%) and myoclonus (100%), followed by behavioral disturbance and ataxia. The mean time from disease onset to death was 6.6 months. Brain MRI showed characteristic hyperintensities in the caudate and putamen with diffusion restriction, and in other regions without restriction. Classical periodic triphasic waves on EEG were observed in 87% of patients, and CSF 14-3-3 protein assay was positive in two of four patients. The study concluded that a strong clinical suspicion, supported by characteristic MRI and EEG findings, is crucial for timely CJD diagnosis.