Plasma Brain-Derived Tau in Prognosis of Large Vessel Occlusion Ischemic Stroke.

BACKGROUND: Large vessel occlusion acute ischemic stroke prognosis improved following the 2015 endovascular therapy (EVT) trials. Blood-based biomarkers may improve outcome prediction. We aimed to assess plasma brain-derived tau (BD-Tau) performance in predicting post-EVT large vessel occlusion acute ischemic stroke outcomes. METHODS: We included 2 temporally independent prospective cohorts of anterior circulation in patients with large vessel occlusion acute ischemic stroke who successfully recanalized post-EVT. We measured plasma BD-Tau, GFAP (glial-fibrillary-acidic-protein), NfL (neurofilament-light-chain), and total-Tau upon admission, immediately, 24 hours, and 72 hours post-EVT. Twenty-four-hour neuroimaging and 90-day functional outcomes were independently assessed using the Alberta Stroke Program Early Computed Tomography Score (good outcome: >7 or unchanged) and the modified Rankin Scale (favorable outcome <3 or unchanged), respectively. Based on the first cohort (derivation), we built a multivariable logistic regression model to predict a 90-day functional outcome. Model results were evaluated using the second cohort (evaluation). RESULTS: In the derivation cohort (n=78, mean age=72.9 years, 50% women), 62% of patients had a good 24-hour neuroimaging outcome, and 45% had a favorable 90-day functional outcome. GFAP admission-to-EVT rate-of-change was the best predictor for early neuroimaging outcome but not for 90-day functional outcome. At admission, BD-Tau levels presented the highest discriminative performance for 90-day functional outcomes (area under the curve, 0.76 [95% CI, 0.65-0.87]; P<0.001). The model incorporating age, admission BD-Tau, and 24-hour Alberta Stroke Program Early Computed Tomography Score achieved excellent discrimination of 90-day functional outcome (area under the curve, 0.89 [95% CI, 0.82-0.97]; P<0.001). The score's predictive performance was maintained in the evaluation cohort (n=66; area under the curve, 0.82 [95% CI, 0.71-0.92]; P<0.001). CONCLUSIONS: Admission plasma BD-Tau accurately predicted 90-day functional outcomes in patients with large vessel occlusion acute ischemic stroke after successful EVT. The proposed model may predict functional outcomes using objective measures, minimizing human-related biases and serving as a simplified prognostic tool for AIS.

Pseudo-eye-of-the-tiger sign in cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS).

The well-known eye-of-the-tiger sign features bilateral and symmetrical changes in the globus pallidus, with a central area of high signal and peripheral low signal on T2-weighted MRI. Although formally considered pathognomonic of pantothenate kinase-associated neurodegeneration (PKAN), there are other neurodegenerative or genetic diseases showing similar findings. Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a late-onset ataxia, that was recently associated with biallelic AAGGG repeat expansion in the RFC1 gene. Although its predominant MRI finding is cerebellar atrophy, there may be other less common associated findings. Our aim is to present two cases of CANVAS with associated (pseudo-)eye-of-the-tiger sign, highlighting the possibility of yet another differential diagnosis for this imaging sign.

Brain MRI in patients with V30M hereditary transthyretin amyloidosis.

BACKGROUND: Central nervous system dysfunction is common in longstanding hereditary transthyretin amyloidosis (ATTRv) caused by the V30M (p.V50M) mutation. Neuropathology studies show leptomeningeal amyloid deposition and cerebral amyloid angiopathy (CAA). Brain MRI is widely used in the assessment of Aß associated CAA but there are no systematic studies with brain MRI in ATTRv amyloidosis. METHODS: we performed 3 T brain MRIs in 16 patients with longstanding (>14 years) ATTRV30M. We additionally retrospectively reviewed 48 brain MRIs from patients followed at our clinic. CNS symptoms and signs were systematically accessed, and MRIs were blindly reviewed for ischaemic and haemorrhagic lesions. RESULTS: in the prospective cohort, we found white matter hyperintensities in 8/16 patients (50%, Fazekas score> =1). There were no relevant microbleeds, large ischaemic or haemorrhagic lesions or superficial siderosis. In the retrospective cohort, microbleeds were found in 5/48 patients (10,4%), two of which with > =20 microbleeds. White matter hyperintensities were found in 20/48 cases (41.7%). White matter lesions, microbleeds and cortical atrophy were not associated with disease duration. CONCLUSIONS: white matter hyperintensities are common in ATTRV30M, irrespective of disease duration. Haemorrhagic lesions are rare, even in patients with longstanding disease, suggesting the existence of other risk factors.

Lissencephaly With Cerebellar Hypoplasia Due To a New RELN Mutation.

Lissencephaly with cerebellar hypoplasia (LCH) is a rare variant form of lissencephaly, its distinctive neuroradiological phenotype being an important investigation clue regarding the potential involved genes, including variants in RELN gene. We report on a case of LCH whose clinical and neuroradiological features led to the identification of a homozygous pathogenic variant in RELN gene that has not been previously reported in the scientific literature.

External Ophthalmoplegia and Brainstem White Matter Lesions: Presentation of Myotonic Dystrophy Type 1.

INTRODUCTION: Myotonic dystrophy type 1 (DM1) is an autosomal dominant condition which phenotype can be extremely variable considering its multisystem involvement, including the central nervous system. Neuromuscular findings are facial and distal extremities muscle weakness, muscle atrophy and myotonia. Standard diagnosis is obtained with molecular testing to detect CTG expansions in the myotonic dystrophy protein of the kinase gene. Brain magnetic resonance imaging typically shows characteristic subcortical white matter (WM) abnormalities located within anterior temporal lobes. CASE REPORT: We present a 39-year-old male patient with a progressive external ophthalmoplegia, facial and limb muscle weakness, percussion myotonia and atypical brain magnetic resonance imaging findings, showing confluent brainstem WM lesions, affecting the pons, a rare radiologic feature in this disorder. Genetic testing confirmed the diagnosis for DM1. CONCLUSION: This presentation with external ophthalmoplegia and brainstem WM loss in DM1 can show an important correlation with clinical findings and have an important diagnostic and prognostic value.

Diagnosis across a cohort of "atypical" atypical and complex parkinsonism.

INTRODUCTION: The diagnostic approach for adulthood parkinsonism can be challenging when atypical features hamper its classification in one of the two main parkinsonian groups: Parkinson's disease or atypical parkinsonian syndromes (APS). Atypical features are usually associated with non-sporadic neurodegenerative causes. METHODS: Retrospective analysis of patients with a working clinical diagnosis of "atypical" APS and complex parkinsonism. "Atypical" APS were classified according to the diagnostic research criteria and the "4-step diagnostic approach" (Stamelou et al. 2013). When not indicated, the final aetiological diagnosis was prospectively assessed. Brain MRI of progressive supranuclear palsy (PSP) look-alikes was reviewed by a neuroradiologist. RESULTS: Among 18 patients enrolled, ten were assigned to the "atypical" APS and eight to the complex parkinsonism group. In the "atypical" APS group, nine patients had PSP and one had corticobasal degeneration. In the PSP group the median magnetic resonance parkinsonism index was 17.1. A final aetiological diagnosis was established for 11 patients, four from the complex parkinsonism (L-2-hidroxiglutaric aciduria and DiGeorge syndrome) and seven from the "atypical" APS (Perry syndrome, postencephalitic PSP, vascular PSP, and MTP-AT6 mitochondrial disease) group. CONCLUSIONS: In this study, the identification of atypical APS features, as proposed in the "4-step diagnostic approach", successfully guided the investigation of alternative diagnoses. Distinctive non-neurodegenerative etiologies causing "atypical" atypical and complex parkinsonism were uncovered, including acquired (post-encephalitis and vascular) and genetic (MTP-AT6 mitochondrial disease mimicking PSP, described for the first time) ones. In the future, accurate clinical identification and distinction between neurodegenerative and non-neurodegenerative parkinsonism etiologies will allow for refining clinical trials.