Alzheimer's disease biomarker utilization at first referral enhances differential diagnostic precision with simultaneous exclusion of Creutzfeldt-Jakob disease.

Most suspected Creutzfeldt-Jakob disease (CJD) cases are eventually diagnosed with other disorders. We assessed the utility of investigating Alzheimer's disease (AD) biomarkers and neurofilament light (NfL) in patients when CJD is suspected. The study cohort consisted of cerebrospinal fluid (CSF) samples referred for CJD biomarker screening wherein amyloid beta 1-42 (Aß1-42), phosphorylated tau 181 (p-tau181), and total tau (t-tau) could be assessed via Elecsys immunoassays (n = 419) and NfL via enzyme-linked immunosorbent assay (ELISA; n = 161). In the non-CJD sub cohort (n = 371), 59% (219/371) had A+T- (abnormal Aß1-42 only) and 21% (79/371) returned A+T+ (abnormal Aß1-42 and p-tau181). In the 48 CJD subjects, a similar AD biomarker profile distribution was observed. To partially address the prevalence of likely pre-symptomatic AD, NfL was utilized to assess for neuronal damage. NfL was abnormal in 76% (25/33) of A+T- subjects 40 to 69 years of age, 80% (20/25) of whom had normal t-tau. This study reinforces AD as an important differential diagnosis of suspected CJD, highlighting that incorporating AD biomarkers and NfL at initial testing is worthwhile.

Levels of plasma brain-derived tau and p-tau181 in Alzheimer's disease and rapidly progressive dementias.

INTRODUCTION: Rapidly progressive dementias (RPDs) are a group of neurological disorders characterized by a rapid cognitive decline. The diagnostic value of blood-based biomarkers for Alzheimer's disease (AD) in RPD has not been fully explored. METHODS: We measured plasma brain-derived tau (BD-tau) and p-tau181 in 11 controls, 15 AD patients, and 33 with RPD, of which 19 were Creutzfeldt-Jakob disease (CJD). RESULTS: Plasma BD-tau differentiated AD from RPD and controls (p = 0.002 and p = 0.03, respectively), while plasma and cerebrospinal fluid (CSF) p-tau181 distinguished AD from RPD (p < 0.001) but not controls from RPD (p > 0.05). The correlation of CSF t-tau with plasma BD-tau was stronger (r = 0.78, p < 0.001) than the correlation of CSF and plasma p-tau181 (r = 0.26, p = 0.04). The ratio BD-tau/p-tau181 performed equivalently to the CSF t-tau/p-tau181 ratio, differentiating AD from CJD (p < 0.0001). DISCUSSION: Plasma BD-tau and p-tau181 mimic their corresponding cerebrospinal fluid (CSF) markers. P-tau significantly increased in AD but not in RPD. Plasma BD-tau, like CSF t-tau, increases according to neurodegeneration intensity.

Rapidly progressive dementia due to intravascular lymphoma: A prion disease reference center experience.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal lymphoma that is characterized by the selective growth of neoplastic cells in blood vessels, representing a potentially treatable cause of rapidly progressive dementia (RPD). Given its diverse clinical and instrumental presentation, it is often misdiagnosed with more common RPD causes, for example, Creutzfeldt-Jakob disease (CJD) or vascular dementia. METHODS: This study presents the clinical and histopathological characteristics of four IVLBCL cases that we diagnosed post-mortem over 20 years among over 600 brain samples received as suspected CJD cases at our prion disease reference center. RESULTS: Our patients exhibited various presenting symptoms, including behavioral disturbances, disorientation, and alertness fluctuations. The diagnostic tests performed at the time, including blood work, cerebrospinal fluid (CSF) analyses, electroencephalography, and neuroimaging, yielded nonspecific and occasionally misleading results. Consequently, the patients were repeatedly diagnosed as variably having CJD, epilepsy, vascular dementia, and encephalitis. The stored CSF samples of two patients tested negative at prion real-time quaking-induced conversion (RT-QuIC), which we performed afterwards for research purposes. Neuropathological analysis revealed a differential involvement of various brain areas, with frontotemporal neocortices being the most affected. CONCLUSIONS: Our results confirm the significant clinical and instrumental heterogeneity of IVLBCL. Neuropathological evidence of the preferential involvement of frontotemporal neocortices, potentially conditioning the clinical phenotype, could be relevant to reach an early diagnosis. Finally, given the therapeutic implications of its misdiagnosis with CJD, we emphasize the utility of prion RT-QuIC as a test for ruling out CJD in these patients.

Rapidly Progressive Dementia in an Elderly Male: Perseverance Becomes the Key to a Rare Diagnosis.

Cognitive impairment in a patient with rapidly progressive dementia (RPD) develops faster than expected for a known dementia syndrome. It poses as a diagnostic challenge for the physician who must identify the diagnosis among a broad spectrum of differentials. Here, we discuss the case of a 60-year-old male who presented with a four-month history of progressive gait disturbance, incoherent talking, dysarthria, hand tremors, and new-onset bladder incontinence. Neurological examination revealed fast saccades, cerebellar dysarthria, hypertonia, and normal power in all four limbs, brisk reflexes, past pointing, intentional tremors, resting myoclonic jerks, and ataxic gait. Initial differentials of progressive paraneoplastic encephalitis, infectious encephalitis, and toxic encephalopathy were considered. However, the results of lumbar puncture and blood investigations-voltage-gated potassium channel (VGKC) antibody and N-methyl-D-aspartate (NMDA) receptor antibody, tumor markers, viral markers being negative and ammonia and lactate levels being normal led us to think of another possibility. With such rapidly progressive dementia, myoclonic jerks, extrapyramidal signs, and cerebellar signs, a diagnosis of Creutzfeldt-Jakob disease (CJD) was taken into consideration. A cerebrospinal fluid (CSF) sample was sent for CSF protein 14-3-3 quantification by enzyme-linked immunosorbent assay (ELISA) and came out positive. During his stay in the hospital, our patient developed multiple complications, and his clinical state progressively worsened. With no signs of improvement and the known fatal nature of the disease, the goals of care were discussed with the family and we all agreed on providing palliative care. The patient passed away on day 15 of hospital admission.

A new genetic variant, presenting as young onset rapidly progressive dementia and parkinsonism.

There are various neurodegenerative or hereditary causes of Parkinsonism. Therefore, clinicians should consider an increasing range of differential diagnoses when facing a patient with Parkinsonism, especially when associated with additional clinical features. Young-onset Parkinsonism, especially when accompanied by features uncommon in idiopathic Parkinson's disease raises the possibility of genetic etiology. Herein, we present a case of a 40-year-old man with genetic Parkinson's disease, presenting with rapidly progressive dementia. This round will describe our approach to this clinical presentation and the unveiling of a rare genetic condition.

Racemose Neurocysticercosis: A Rare Cause of Rapidly Progressive Dementia-A Case Report.

This report describes the case of a 68-year-old woman with episodic memory impairment for 6 months. Brain magnetic resonance imaging detected multiple extra-axial variable-sized cystic lesions in the left medial temporal lobe, suprasellar cistern, and perimesencephalic cistern. The serum and cerebrospinal fluid tested positive for Taenia solium, confirming racemose neurocysticercosis. Albendazole and praziquantel were administered for 6 months and prednisolone for 1 month. After 3 months, her symptoms resolved. Despite its rarity, racemose neurocysticercosis should be considered in patients with rapidly progressive dementia and cystic brain lesions.

Case report: Two clusters of Creutzfeldt-Jakob disease cases within 1 year in West Michigan.

Background: Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and uniformly fatal neurodegenerative disease. The reported incidence of CJD is 1 to 2 per million people worldwide annually, with fewer than 1,000 cases in the United States per year. In this study, we report a unique case series on temporo-spatial clusters of CJD cases in West Michigan. Methods: A total of five CJD cases consisting of two temporal clusters were seen from July 2021 to June 2022 at Corewell Health West hospitals. All patients had brain MRI, EEG, and CSF tests. Four patients underwent autopsies. Results: All patients' MRIs showed characteristic CJD patterns. Four patients had positive CJD panels in CSF. One patient had typical CJD EEG findings. Four patients were confirmed as sporadic CJD by autopsy. All patients died within 3 months after CJD was suspected. Discussion: All patients lived within a 90-mile radius of Grand Rapids, MI, and two lived in the same county. West Michigan has a population of 1.6 million people, and the four counties where five patients lived have a combined population of 395,104, indicating CJD's new case rate of 3.1 and 12.5 per million people, respectively. Corewell Health is one of the three major healthcare systems in West Michigan. The actual incidence of CJD in West Michigan is likely even higher. This dense temporal and spatial cluster of CJD cases poses a serious public health challenge and warrants urgent investigation.

Case report: A longitudinal study of an unusual rapidly progressive dementia case.

It is daunting to determine the etiology of rapidly progressive dementia (RPD), which includes metabolic, neoplastic, infectious, autoimmune, neurodegenerative and other conditions. Herein, we illustrate an unusual case of a patient primarily exhibiting RPD, overlapping sleep dysfunction, psychosis and abnormal movement, which was finally defined as anti-IgLON5 disease, a novel and rare autoimmune encephalopathy. Furthermore, we longitudinally described his cognitive and psychological performance in detail, and determined that early initiation of immunotherapy in this patient did not result in a good outcome. These data highlight anti-IgLON5 disease as a possible differential diagnosis in patients with RPD.

Prevalence and outcomes of rapidly progressive dementia: a retrospective cohort study in a neurologic unit in China.

BACKGROUND: Rapidly progressive dementia (RPD) is a syndrome originating from various diseases. Recent advances have allowed a better understanding of its categories and spectrum; however, it remains challenging to make an accurate differential diagnosis and prognosis prediction. METHODS: This study was a retrospective evaluation of all participants admitted to the neurology department of a single center in China from January 2015 to December 2019. The screened patients met the RPD criteria and their characteristics were collected to explore a diagnostic pattern of RPD. In addition, outcomes of RPD were evaluated with the Glasgow Outcome Scale (GOS), activities of daily living scale (ADL), and simplified Mini-Mental State Examination (MMSE), and different prognostic analysis methods were performed to determine the prognostic factors of RPD. RESULTS: A total of 149 RPD patients among 15,731 inpatients were identified with an average MMSE value of 13.0 ± 4.6 at baseline. Etiological epidemiology revealed infectious, neurodegenerative and toxic/metabolic diseases as the three largest groups, accounting for 26.2%, 20.8% and 16.8% of all cases, respectively. In particular, prevalence rates of Creutzfeldt-Jakob disease (13.4%), Alzheimer's disease (11.4%), carbon monoxide poisoning (8.1%), neurosyphilis (5.4%) and dementia with Lewy bodies (5.4%) were highest in this series. A recommended diagnostic framework for RPD etiology was thus established. Follow-up evaluations showed a negative correlation between age and GOS scores (r=-0.421, P < 0.001), as well as age and simplified MMSE scores (rs =- 0.393, P < 0.001), and a positive correlation between age and ADL scores (rs =0.503, P < 0.001), and significantly different GOS, ADL and simplified MMSE scores across various etiologies (P = 0.003; F = 9.463, P < 0.001; F = 6.117, P < 0.001). CONCLUSION: Infectious, neurodegenerative and toxic-metabolic entities were the most common RPD categories, and establishing a practical approach to RPD etiology would allow better disease management.

Rapidly Progressive Corticobasal Degeneration Mimicking Brainstem Encephalitis.

Background: Corticobasal degeneration (CBD) may have a rapidly progressive (RP) clinical course, mimicking other neurological conditions. Objectives: To describe a neuropathologically proven case of RP-CBD in a patient initially diagnosed with immune-mediated brainstem encephalitis. Methods: Retrospective data collection from electronic records and authorized video material. Results: A 51-year-old man presented with bilateral ptosis, diplopia, and dysphagia. The diagnostic workup was negative for myasthenic syndromes. He progressively developed cognitive dysfunction with frontal release signs and asymmetric parkinsonism. Cerebrospinal fluid evaluation revealed 4 leukocytes/uL, 0.32 g/L proteins, 0.85 g/L glucose, and absent oligoclonal bands. Weakly positive anti-PNMA2 (Ma2/Ta) antibodies were present, and magnetic resonance imaging showed a T2 hyperintensity involving the midbrain and pons. Based on these features, the diagnosis of immune-mediated brainstem encephalitis was considered. The patient did not improve after several cycles of methylprednisolone, intravenous immunoglobulin, and plasma exchange. At 1 year after onset, he developed horizontal and vertical gaze limitation and worsening of the parkinsonism and cognitive dysfunction. By age 53, he was severely disabled, requiring percutaneous gastrostomy for feeding. Anti-IgLON5 was negative. He fulfilled the clinical criteria for probable progressive supranuclear palsy. He died from pneumonia at age 54. The neuropathological examination revealed a 4-repeat tauopathy with features of CBD with extensive involvement of the brainstem. Conclusions: RP-CBD may resemble brainstem encephalitis. The severity of brainstem and upper spinal cord pathology in the postmortem examination correlated with the clinical and imaging features.

Sporadic Creutzfeldt-Jakob disease in Northern Tasmania.

Creutzfeldt-Jakob disease is a rare and incurable form of rapidly progressive neurodegenerative disease. The disease is fatal, and most patients die within 1 year of diagnosis. Clinical features include progressive cognitive dysfunction, delusions or hallucinations, cerebellar ataxia, myoclonus, visual disturbances, extrapyramidal signs and eventually akinetic mutism. Most patients present with varied clinical presentation, hence making it difficult to diagnose at an early stage. We report five cases of sporadic Creutzfeldt-Jakob disease presenting to a Tasmanian hospital in Australia over a period of 52 months. We highlight significant clinical features in all our patients including few atypical presentations, emphasise on relevant clinical biomarkers and illustrate characteristic abnormalities on electroencephalogram and neuroimaging.

Clinical Correlates of Cerebrospinal Fluid 14-3-3 Protein in Non-Prion Rapid Progressive Dementia.

BACKGROUND: The 14-3-3 protein in cerebrospinal fluid (CSF) is a suitable biomarker for the diagnosis of Creutzfeldt-Jakob disease (CJD). However, it has also been detected in various non-prion-related rapidly progressive dementia (RPD), which affected its diagnostic performance and clinical utilization. OBJECTIVE: To investigate the general disease distribution with positive 14-3-3 result and to evaluate the association between CSF 14-3-3 protein and the clinical features in patients with non-prion RPD. METHODS: A total of 150 patients with non-prion RPD were enrolled. The clinical data were collected and CSF 14-3-3 test was performed for all patients. The distribution of various diseases with a positive 14-3-3 result was analyzed and the association of CSF 14-3-3 with clinical features was tested. RESULTS: The CSF 14-3-3 protein was detected in 23.3% of non-prion RPD patients, and the most frequent diagnoses were autoimmune encephalitis (22.9%) and neurodegenerative disease (22.9%). CSF 14-3-3 protein was more common in older patients (p = 0.028) and those presenting myoclonus (p = 0.008). In subgroup analysis, the positive 14-3-3 test was more common in neurodegenerative disease with a long time from the symptom onset to CSF 14-3-3 test (p = 0.014). CONCLUSION: CSF 14-3-3 protein could be detected in a broad spectrum of non-prion RPD. In particular, patients with autoimmune encephalitis and rapidly progressive neurodegenerative diseases and those with myoclonus have a greater likelihood of a positive 14-3-3 result. These results could help clinicians interpret the results of CSF 14-3-3 protein more reasonably.

A Devastating Neurological Disorder: Anti-Dipeptidyl-Peptidase-Like Protein 6 (DPPX) Encephalitis Causing Rapidly Progressive Dementia.

Rapidly progressive dementia (RPD) is caused by a heterogeneous group of neurological disorders, and the prototype is Creutzfeldt-Jakob disease (CJD). However, treatable causes including autoimmune encephalitis are often underrecognized and undertreated. A 72-year-old female patient was admitted with a 10-month history of rapidly progressive cognitive decline, visual hallucinations, paranoid behavior, diarrhea, and an 18-kg unintentional weight loss. On the physical exam, she was only oriented to the person and demonstrated an exaggerated startle response with diffuse rigidity. The initial clinical suspicion included CJD versus autoimmune encephalitis. Comprehensive laboratory testing, thyroid peroxidase, thyroglobulin antibodies, and autoimmune encephalitis panel were negative. The EEG showed mild to moderate diffuse slowing without any epileptiform abnormalities. An MRI brain revealed mild hippocampal atrophy. CSF testing revealed mild lymphocytic pleocytosis; RT-QuIC analysis and 14-3-3 protein were negative. There was no clinical improvement after treatment with IV steroids and IVIG. Repeated autoimmune encephalitis panel testing performed on a research basis was positive for dipeptidyl-peptidase-like protein 6 (DPPX) antibodies in serum and CSF. Unfortunately, our patient passed away before additional treatment could be attempted. Anti-DPPX encephalitis is a rare autoimmune disorder and an unrecognized cause of RPD. Early diagnosis and rapid escalation of treatment are imperative to avoid devastating neurological consequences.

Experiencia con la enfermedad de Creutzfeldt-Jakob de un único centro de referencia en México. Análisis de una serie de casos / Experience with Creutzfeldt-Jakob disease in a single referral center in Mexico. Case series

Resumen Introducción: La enfermedad de Creutzfeldt-Jakob (ECJ) es una enfermedad del sistema nervioso central rápidamente progresiva y mortal causada por priones. Objetivo: Presentar las principales características clínicas y paraclínicas de pacientes con probable ECJ en un centro de referencia de América Latina. Métodos: Estudio retrospectivo de pacientes diagnosticados con demencia rápidamente progresiva entre 2014 y 2019. Se incluyeron características clínicas, demográficas, del electroencefalograma, imágenes por resonancia magnética, proteína 14-3-3 y tomografía por emisión de positrones (PET), cuando estaba disponible. Resultados: Veinticuatro pacientes cumplieron con los criterios de ECJ esporádica (75 % mujeres), la edad media fue de 59.29 ± 11.67 años, la duración de la enfermedad desde el inicio de los síntomas hasta el ingreso hospitalario fue de 7.41 ± 6.54 meses y las primeras manifestaciones más comunes fueron las alteraciones del comportamiento (41.7 %). Los complejos de ondas delta prevalecieron en el electroencefalograma (54.2 %), la hiperintensidad cortical en la resonancia magnética (83.3 %) y el hipometabolismo frontal en la PET (37.5 %). En el análisis del líquido cefalorraquídeo, siete casos mostraron proteína tau total positiva; cinco, proteína 14-3-3 positiva; y tres, proteína tau hiperfosforilada positiva. Conclusiones: Existe importante heterogeneidad clínica en cuanto a los síntomas iniciales. Los hallazgos de las pruebas auxiliares coincidieron con los de otras series.

Abstract Introduction: Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and fatal central nervous system disease caused by prions. Objective: To present the main clinical and paraclinical characteristics of patients with probable CJD in a referral center of Latin America. Methods: Retrospective study of patients diagnosed with rapidly progressive dementia between 2014 and 2019. Clinical, demographic, electroencephalogram, magnetic resonance imaging, and 14-3-3 protein characteristics were included, as well as positron-emission tomography (PET) data when available. Results: Twenty-four patients met the criteria for sporadic CJD (75% were women). Mean age was 59.29 ± 11.67 years, while mean disease duration from symptom onset to hospital admission was 7.41 ± 6.54 months. The most common first symptom was behavioral changes (41.7%). Delta wave complexes prevailed (54.2%) on electroencephalogram, cortical hyperintensity (83.3%) on magnetic resonance and frontal hypometabolism (37.5%) on PET. Seven cases showed positive total Tau; five, positive 14-3-3 protein; and three, positive phosphorylated tau on cerebrospinal fluid analysis. Conclusions: There is significant clinical heterogeneity regarding initial symptoms. Auxiliary test findings were consistent with those of other series.

Vascular intracranial malformations and dementia: An under-estimated cause and clinical correlation. Clinical note.

Cerebrovascular malformations (CVMs) such as arteriovenous malformations (AVMs) or dural arteriovenous fistulas (DAVFs) represent a possible source of intracranial hemorrhage, but these malformations can also manifest with neurologic disorders secondary to ischemic penumbra from vascular steal. In the latter case, the clinical manifestations are less obvious and characteristic, and may include a varied clinical spectrum ranging from focal deficits to generalized malfunction of the brain parenchyma resulting in dementia. Dementias secondary to CVMs constitute a probably underestimated subpopulation of patients of great interest because they present with devastating but potentially reversible cognitive impairment. We examined the pertinent literature regarding the clinical manifestations of CVMs characterized by cognitive impairment and describe the distinctive clinical features. Our results confirm that cognitive impairment is one of the clinical manifestations of CVMs and is a frequently misrecognized and often late-diagnosed cause of reversible dementia.

Creutzfeldt-Jakob Disease: A Case Report and Literature Review for Understanding the Big Picture.

Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive neurodegenerative disorder that has an invariably fatal outcome. Aside from rapidly progressive dementia, this condition manifests as myoclonus, cerebellar, pyramidal, extrapyramidal, visual, and psychiatric symptoms. On the other hand, nonspecific symptoms might be difficult to diagnose, leading to a late or incorrect diagnosis. Given its high fatality, most patients die within 12 months of the disease's onset. This case report describes a healthy man who presented with cerebellar and pyramidal signs along with memory loss worsening over six weeks. He also had indications of corticobasal degeneration, such as myoclonus and alien limb syndrome, but with reasonably maintained cognition. These signs are all non-specific, and premortem diagnosis is typically difficult and challenging owing to a lack of knowledge and clinical suspicion. However, after a thorough and extensive investigation, CJD was diagnosed. Despite the fact that CJD is a rare disease, it should always be included in the differential diagnosis whenever neuropsychological manifestations are present. Nevertheless, CJD can be successfully and promptly ruled out with a detailed clinical examination and appropriate investigation.

A case report of cerebral venous sinus thrombosis presenting with rapidly progressive dementia.

Background: Cerebral venous sinus thrombosis (CVST) is a rare but serious and treatable cause of neurologic symptoms. Due to the variable clinical presentation, CVST was often misdiagnosed. According to published case reports, common clinical manifestations of CVST include headache, focal neurological deficit, epilepsy, papilledema, etc. It is rare, nevertheless, to mention cases of rapidly progressive dementia (RPD). Case presentation: We reported a case of a 62-year-old retired male accountant, a Han Chinese from eastern China, who initially presented with slow response and memory decline. Until 2 months later, his memory declined and slow response deteriorated significantly, and he could not even complete simple tasks like brushing his teeth, washing his face, washing his feet, and dressing himself, and sometimes developed fecal incontinence. His neuropsychological test demonstrated severe cognitive decline. The cerebrospinal fluid (CSF) studies revealed markedly high opening pressure (260 mm of water), and coagulation tests indicated a mild elevation of D-Dimer of 1.19 mg/L. The magnetic resonance venography (MRV) showed thrombosis of the left transverse sinus, sigmoid sinus, and jugular venous bulb and was diagnosed as CVST. He switched from subcutaneous low molecular weight heparin (LMWH) and transitioned to oral anticoagulants at the time of discharge. The repeated CSF studies revealed normal opening pressure. After 5 days of anticoagulant treatment, his symptoms considerably improved, and a 1-month follow-up revealed that he had fully healed with no signs of recurrence. Conclusion: This case demonstrated the clinical heterogeneity of CVST, which should be taken into account for differential diagnosis of RPD. This case study also offered fresh data for the categorization of the clinical traits and the diagnosis of CVST.

SORL1 gene mutation and octapeptide repeat insertion in PRNP gene in a case presenting with rapidly progressive dementia and cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) has been associated with a variety of neurodegenerative disorders, included prion diseases and Alzheimer's disease; its pathophysiology is still largely unknown. We report the case of an 80-year-old man with rapidly progressive dementia and neuroimaging features consistent with CAA carrying two genetic defects in the PRNP and SORL1 genes. METHODS: Neurological examination, brain magnetic resonance imaging (MRI), electroencephalographic-electromyographic (EEG-EMG) polygraphy, and analysis of 14-3-3 and tau proteins, Aß40, and Aß42 in the cerebrospinal fluid (CSF) were performed. The patient underwent a detailed genetic study by next generation sequencing analysis. RESULTS: The patient presented with progressive cognitive dysfunction, generalized myoclonus, and ataxia. Approximately 9 months after symptom onset, he was bed-bound, almost mute, and akinetic. Brain MRI was consistent with CAA. CSF analysis showed high levels of t-tau and p-tau, decreased Aß42, decreased Aß42/Aß40 ratio, and absence of 14.3.3 protein. EEG-EMG polygraphy demonstrated diffuse slowing, frontal theta activity, and generalized spike-waves related to upper limb myoclonus induced by intermittent photic stimulation. Genetic tests revealed the presence of the E270K variant in the SORL1 gene and the presence of a single octapeptide repeat insertion in the coding region of the PRNP gene. CONCLUSIONS: The specific pathogenic contribution of the two DNA variations is difficult to determine without neuropathology; among the possible explanations, we discuss the possibility of their link with CAA. Vascular and degenerative pathways actually interact in a synergistic way, and genetic studies may lead to more insight into pathophysiological mechanisms.