Plasma p-tau212 antemortem diagnostic performance and prediction of autopsy verification of Alzheimer's disease neuropathology.

Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer's disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217. Here, we examined the diagnostic utility of plasma p-tau212. In five cohorts (n = 388 participants), plasma p-tau212 showed high performances for AD diagnosis and for the detection of both amyloid and tau pathology, including at autopsy as well as in memory clinic populations. The diagnostic accuracy and fold changes of plasma p-tau212 were similar to those for p-tau217 but higher than p-tau181 and p-tau231. Immunofluorescent staining of brain tissue slices showed prominent p-tau212 reactivity in neurofibrillary tangles that co-localized with p-tau217 and p-tau202/205. These findings support plasma p-tau212 as a peripherally accessible biomarker of AD pathophysiology.

Plasma p-tau212: antemortem diagnostic performance and prediction of autopsy verification of Alzheimer's disease neuropathology.

Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer's disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize tau forms phosphorylated additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that is specific to p-tau212 without cross-reactivity to p-tau217. Thereafter, we examined the diagnostic utility of plasma p-tau212. In five cohorts (n=388 participants), plasma p-tau212 showed high performances for AD diagnosis and for the detection of both amyloid and tau pathology, including at autopsy as well as in memory clinic populations. The diagnostic accuracy and fold changes of plasma p-tau212 were similar to those for p-tau217 but higher than p-tau181 and p-tau231. Immunofluorescent staining of brain tissue slices showed prominent p-tau212 reactivity in neurofibrillary tangles that co-localized with p-tau217 and p-tau202/205. These findings support plasma p-tau212 as a novel peripherally accessible biomarker of AD pathophysiology.

Isolated arteritis misdiagnosed as bilateral orbital tumors in a patient with acute ischemic stroke.

Vasculitis is a heterogeneous group of disorders characterized by multifocal segmental inflammation of the small and medium vessels of the central nervous system. The predominant symptoms of cerebral vasculitis are stroke, headache, and encephalopathy. Additional symptoms include seizures, cranial nerve palsies, and myelopathy. Imaging techniques play a crucial role in identifying the diagnosis of vasculitis and demonstrating brain involvement. An 89-year-old woman with permanent atrial fibrillation developed an embolic stroke. In treatment, intravenous thrombolysis and thrombectomy with complete antegrade reperfusion of the left middle cerebral artery was used, without the clinical effectiveness. Brain MRI revealed bilateral oval lesions in medial parts of the orbits, which were initially misinterpreted as orbital tumors. Final diagnosis confirmed thickened arterial walls as orbital changes due to inflammatory arteritis. Ten days later, follow-up MRI was performed and showed complete regression of the orbital masses. Primary central nervous system vasculitis, manifesting as acute ischemic stroke, may be reversible with early systemic thrombolytic treatment.

Regulation of microRNA Expression in Sleep Disorders in Patients with Epilepsy.

The effects of epilepsy on sleep and the activating effects of sleep on seizures are well documented in the literature. To date, many sleep-related and awake-associated epilepsy syndromes have been described. The relationship between sleep and epilepsy has led to the recognition of polysomnographic testing as an important diagnostic tool in the diagnosis of epilepsy. The authors analyzed the available medical database in search of other markers that assess correlations between epilepsy and sleep. Studies pointing to microRNAs, whose abnormal expression may be common to epilepsy and sleep disorders, are promising. In recent years, the role of microRNAs in the pathogenesis of epilepsy and sleep disorders has been increasingly emphasized. MicroRNAs are a family of single-stranded, non-coding, endogenous regulatory molecules formed from double-stranded precursors. They are typically composed of 21-23 nucleotides, and their main role involves post-transcriptional downregulation of expression of numerous genes. Learning more about the role of microRNAs in the pathogenesis of sleep disorder epilepsy may result in its use as a biomarker in these disorders and application in therapy.

Cerebrospinal fluid α synuclein concentrations in patients with positive AD biomarkers and extrapyramidal symptoms.

Extrapyramidal symptoms (EP) are not uncommon in Alzheimer's Disease (AD); when present, they negatively influence the course of the disorder. A large proportion of AD patients shows concomitant Lewy bodies' pathology post mortem. Total α Synuclein (αSyn) concentrations are frequently increased in the cerebrospinal fluid (CSF) of AD patients, but are decreased in Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). αSyn CSF concentrations in AD patients with EP (EP+) have not been reported so far. αSyn and the four Neurochemical Dementia Diagnostics (NDD) CSF biomarkers, (Aß1-42, Aß42/40, Tau, and pTau181), interpreted according to the Erlangen Score algorithm, were measured in patients with positive NDD results and presence of extrapyramidal symptoms (NDD + / EP+; n = 26), in patients with positive NDD results and absence of extrapyramidal symptoms (NDD+ / EP-; n = 54), and in subjects with negative NDD results (NDD-; n = 34). Compared to the NDD- controls (379.8 ± 125.2 pg/mL), NDD+ patients showed, on average, highly significantly increased CSF αSyn (519 ± 141.3 pg/mL, p < 0.01), but without differences between NDD+ / EP+ and NDD+ / EP- subgroups (p = 0. 38). Moderate but highly significant association was observed between concentrations of αSyn and Tau (r = 0.47, p < 0.01) and pTau181 (r = 0.65, p < 0.01). Adjusted for diagnoses, age, and sex, subjects with more advanced neurodegeneration on neuroimaging showed significantly lower αSyn concentrations (p < 0.02). In the setting AD versus controls, the area under the receiver operating characteristic (ROC) curve was 0.804 [0.712; 0.896] with the sensitivity and the specificity of 0.863 and 0.618, respectively. αSyn in AD patients does not differentiate between subjects with- and without EP. Its increased average concentration reflects probably neurodegenerative process, and is not specific for any pathophysiologic mechanisms. Further studies are necessary to explain the role of CSF αSyn as a potential biomarker.

Cerebral small vessel disease: A review.

Cerebral small vessel disease (CSVD) is the most common, chronic and progressive vascular disease. The changes affect arterioles, capillaries and small veins supplying the white matter and deep structures of the brain. It is the most common incidental finding on brain scans, especially in people over 80 years of age. Magnetic resonance imaging (MRI) plays a key role in the diagnosis of CSVD. The nomenclature and radiological phenotypes of CSVD were published in 2013 based on the unified position of the so-called Centres of Excellence in Neurodegeneration. The disease is characterized by a diverse clinical and radiological picture. It is primarily responsible for stroke incidents, gait disturbances, depression, cognitive impairment, and dementia in the elderly. The CSVD contributes to about 20% of strokes, including 25% of ischemic strokes and 45% of dementias. Common causes of CSVD include arteriosclerosis, cerebral amyloid angiopathy (CAA), genetic small vessel angiopathy, inflammation and immune-mediated small vessel diseases, and venous collagenosis. There is no causal treatment and management is mainly based on combating known risk factors for cardiovascular disease (CVD).

Predictive factors in post-stroke epilepsy: Retrospective analysis.

BACKGROUND: Cerebrovascular disease is an important cause of epilepsy. The incidence may significantly vary (from 2.3% to 43%). Post-stroke seizures occur within 2 weeks of stroke onset (as early-onset seizures) or 2 weeks after a stroke (as late-onset seizures). OBJECTIVES: To retrospectively evaluate and differentiate predictive factors for post-stroke seizures. MATERIAL AND METHODS: We retrospectively analyzed the medical histories of 164 adult patients diagnosed with post-stroke seizures but no epilepsy recognized prior to the stroke who were hospitalized at the Neurology Clinic of Wroclaw Medical University between 2012 and 2018. The seizures were classified according to the criteria of the International League Against Epilepsy (ILAE) from 2017. The relevant demographic data, type of stroke (ischemic/hemorrhagic), time of occurrence of seizures in relation to the type of stroke, score on the modified Rankin Scale, presence of cardiovascular risk factors, electroencephalography (EEG) recording, and antiepileptic treatment (AED) were collected. In the case of ischemic stroke (IS), the size of the stroke lesion was rated on the ASPECTS scale. RESULTS: The study involved 164 patients (average age = 68.83 years), including 86 men (average age = 66.2 years). In 20 out of 164 patients, the seizures were associated with hemorrhagic stroke (HS); in 144 out of 164 patients, the post-stroke epilepsy was associated with IS. Generalized tonic-clonic seizures occurred in 101 out of 164 patients, focal aware seizures occurred in 19 out of 164 patients and focal impaired-awareness seizures occurred in 44 out of 164 patients. CONCLUSIONS: Our study has confirmed that generalized seizures occur mostly after an IS and are late complications of it. Early-onset seizures occur mostly after HS associated with severe disability. Seizures are more likely to happen due to the cortical location of the stroke. There is a shift from generalized to focal seizures with an increase in the extent of IS as evaluated using the ASPECTS scale.

Plasma tau protein and Aß42 level as markers of cognitive impairment in patients with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder with a characteristic clinical picture. Apart from classical movement disorders, a significant role is also played by non-motor symptoms, in particular cognitive impairments, which have a significant impact on the quality of life of the patients. Tau protein and amyloid beta are well-known non-specific biomarkers in Alzheimer's disease (AD). OBJECTIVES: The study assessed the practical value of determining tau protein and amyloid beta (Aß42) in the blood serum of patients with PD and their relationship with cognitive impairments, radiographic image and the used dose of L-DOPA. MATERIAL AND METHODS: The neuropsychological assessment was carried for 64 patients with PD. The levels of amyloid beta 1-42 (Aß42) and tau proteins in serum were also measured. RESULTS: The Aß42 level in the serum was statistically higher in patients with longer duration of the disease (p < 0.05) and those who were taking a higher dose of L-DOPA (p < 0.05). The average level of tau protein in the serum was slightly lower in the study groups than in the control group and showed no statistical significance. No correlation was found between the levels of tau protein and Aß42 and the results of neuropsychological tests. Tau protein correlated with hippocampal atrophy (p < 0.05). CONCLUSIONS: Serum levels of Aß42 and tau protein in PD may be a useful marker for the assessment of cognitive impairments. The role of L-DOPA in the process of dementia in PD remains unclear.

Seasonal variations in the occurrence of transient global amnesia (TGA).

BACKGROUND: Transient global amnesia (TGA) is a rare, benign condition characterised by a sudden deficit of anterograde and retrograde memory that usually lasts for a few hours and is not accompanied by other focal neurological symptoms or signs. Its aetiology is still unclear. Various events or activities may trigger TGA. Evidence of seasonal variations in the appearance of TGA is inconsistent. METHODS: We retrospectively analysed the medical history of 114 adult patients with diagnosed TGA, hospitalised at two neurology departments in Wroclaw from 2008 to 2014. We reviewed risk factors, trigger points, and occurrence in each month of the year in our patient population. RESULTS: Over this seven-year period, 114 patients were diagnosed with TGA. The annual occurrence ranged from 13 to 22 hospitalisations. The mean age of the patients was 64 years. There were 36 TGA events in men and 78 in women. TGA occurred most frequently in spring (36%) and summer (30%), with the incidence peaking during March. CONCLUSIONS: Our findings suggest that there is a relationship between the season of the year and the probability of TGA.

Cerebral venous thrombosis as a diagnostic challenge: Clinical and radiological correlation based on the retrospective analysis of own cases.

BACKGROUND: Cerebral venous thrombosis (CVT) is a rare condition which constitutes 0.5-1% of all strokes. The clinical and radiological picture of CVT is non-specific and can mimic other disorders. OBJECTIVES: The aim of the study was to retrospectively evaluate and correlate clinical and radiological symptoms presented by patients with CVT, both in the initial and follow-up neurological and neuroimaging examinations, with a special emphasis on diagnostic difficulties. MATERIAL AND METHODS: Material consisted of 11 patients with CVT (7 women, 4 men). The average age was 43.5, ranging from 23 to 69 years. Clinical symptoms, laboratory findings, risk factors and the results of neuroimaging examinations including CT, MRI and DSA were retrospectively analyzed and correlated. RESULTS: All subjects developed superficial CVT and 1 also deep CVT, with no parenchymal lesions in 2 cases, non-hemorrhagic infarctions in 3 and hemorrhagic lesions in 6 subjects. The most frequent symptoms were headache, seizures and hemiparesis. The major risk factors were hormonal therapies in women and congenital thrombophilia. Factors influencing the clinical course and outcome the most were location and type of brain lesions, with hemorrhagic cortical infarctions bringing the worst prognosis and being associated with the highest rate of persistent neurological deficits, despite the rate of vessel recanalization. CONCLUSIONS: In our opinion, quick diagnosis before parenchymal hemorrhagic lesions are visible on CT is of crucial importance and requires a constant alertness and good cooperation of neurologists and radiologists, especially in emergency settings.

Visual and somatosensory phenomena following cerebral venous infarction.

BACKGROUND: The most frequent clinical presentation of occipital or visual tract lesion is hemianopsia or quadrantanopsia. However, damage to the primary or secondary visual cortex can also manifest as visual hallucinations (photopsiae or complex phenomena). We report visual and somatosensory phenomena following cerebral venous infarction based on a study of a patient with a history of recent head injury. CASE PRESENTATION: We report a 61-year-old man with a history of recent head injury presented with a headache of two weeks duration. He was complaining of transient visual abnormalities, which he described as impaired ability to recognize faces, dark spots moving in the visual field and distorted contours of an objects. Clinical examination showed a balance disorder with no evidence of visual deficit. During further observation the patient started to experience more complex visual and sensory phenomena of: waving of the ceiling, clouds that he could form and feel, he had an impression of incorrect sizes of given objects, he could see a nonexistent pack of cigarettes and the character from the arcade game Pac-Man "eating" an existing drip stand. CONCLUSIONS: The patient mentioned above possessing simple and complex visual and somatosensory hallucinations and illusions in the course of venous stroke. A possible mechanism involves irritation of cortical centers responsible for visual processing.

The Usefulness of the TOAST Classification and Prognostic Significance of Pyramidal Symptoms During the Acute Phase of Cerebellar Ischemic Stroke.

Cerebellar stroke is a rare condition with very nonspecific clinical features. The symptoms in the acute phase could imitate acute peripheral vestibular disorders or a brainstem lesion. The aim of this study was to assess the usefulness of the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification in cerebellar stroke and the impact of clinical features on the prognosis. We retrospectively analyzed 107 patients with diagnosed ischemic cerebellar infarction. We studied the clinical features and compared them based on the location of the ischemic lesion and its distribution in the posterior interior cerebellar artery (PICA), superior cerebellar artery (SCA), and anterior inferior cerebellar artery (AICA) territories. According to the TOAST classification, stroke was more prevalent in atrial fibrillation (26/107) and when the lesion was in the PICA territory (39/107). Pyramidal signs occurred in 29/107 of patients and were more prevalent when the lesion was distributed in more than two vascular regions (p = 0.00640). Mortality was higher among patients with ischemic lesion caused by cardiac sources (p = 0.00094) and with pyramidal signs (p = 0.00640). The TOAST classification is less useful in assessing supratentorial ischemic infarcts. Cardioembolic etiology, location of the ischemic lesion, and pyramidal signs support a negative prognosis.

[Cerebellar stroke]. / Udar mózdzku.

Cerebellar stroke belongs to a group of rare diseases of vascular origin. Cerebellum, supplied by three pairs of arteries (AICA, PICA, SCA) with many anastomoses between them is less susceptible for a stroke, especially ischemic one. Diagnosis of the stroke in this region is harder due to lower sensibility of commonly used CT of the head in case of stroke suspicion. The authors highlight clinical symptoms distinguishing between vascular territories or topographical locations of the stroke, diagnostic procedures, classical and surgical treatment, the most common misdiagnoses are also mentioned. The authors suggest a diagnostic and therapeutic algorithm development, including rtPA treatment criteria for ischemic cerebellar stroke.