SQSTM1 Pro392Leu presenting as a corticobasal syndrome with progressive nonfluent aphasia.

Corticobasal syndrome is generally considered to be a sporadic condition. There are familial and isolated genetic cases, associated with GRN, MAPT, c9orf72 or PNRP variants. Some reports implicate other genes: LRRK2, CHMP2B, GBA, CYP27A1, PSEN1, APP, TARDBP and TBK1. Here, we report a case of a patient carrying a SQSTM1 Pro392Leu variant. We report a 57-year-old right-handed-woman with a history of progressive speech impairment, marked right side rigidity and bradykinesia, with rest tremor and stimulus sensitive myoclonus. She had predominantly right-sided apraxia. She had right side agraphestesia and astereognosis. MRI showed asymmetrical left frontotemporoparietal atrophy. DaTSCAN showed predominantly left involvement, PiB-PET was negative. CSF NfL was of 9356.5pg/mL. She carried a heterozygous variant P392L in SQSTM1. This case report expands the spectrum of phenotypes associated with SQSTM1 pathogenic variants. It also expands the list of genes associated with corticobasal syndrome, supporting the involvement of the ubiquitin-proteasome system in this condition.

Neuroimaging, serum biomarkers, and patient characteristics as predictors of upper limb functioning 12 weeks after acute stroke: an observational, prospective study.

OBJECTIVE: To evaluate the potential of neuroimaging, serum biomarkers, stroke etiology, and clinical characteristics as predictors of upper limb functioning 12 weeks after stroke. METHODS: This was a prospective, observational study of patients (18-85 years-old) hospitalized due to acute ischemic stroke in the territory of the middle cerebral artery. Patients were hospitalized at a stroke rehabilitation center, where they underwent a standardized rehabilitation program. Clinical, imagiology, laboratory (biomarkers: C-reactive protein, D-dimer, and fibrinogen, and S100 calcium binding protein ß [S100ß]), and functionality assessments were conducted four different times: within 24 hours, and at 48 hours, 3 weeks, and 12 weeks after acute stroke. RESULTS: Upper limb functioning at 12 weeks was significantly associated with Alberta Stroke Program Early CT Score (ASPECTS) score (OR:2.012 [CI:1.349-3.000]; P = 0.001) and S100ß protein levels (OR:0.997 [CI:0.994-0.999]; P = 0.007). Advanced age was associated with poor upper limb functioning. S100ß protein levels < 140.5 ng/L at 48 hours and ASPECTS scores ≥ 7.5 within 24 hours of admission predicted good hand functioning at 12 weeks. Upper limb functioning and general functioning were significantly correlated (P < 0.001), with strong negative correlations (all correlation coefficients ≤-0.586) for all comparisons. CONCLUSION: ASPECTS score ≥ 8 within 24 hours and S100ß protein < 140.5 ng/L at 48 hours predict better upper limb functioning, while advanced age predicts worse upper limb functioning 12 weeks after stroke.

S100ß Protein as a Predictor of Poststroke Functional Outcome: A Prospective Study.

BACKGROUND: Stroke is one of the leading causes of disability worldwide. Early prediction of poststroke disability using clinical models is of great interest, especially in the rehabilitation field. Although some biomarkers and neuroimaging techniques have shown potential predictive value, there are still insufficient data to support their clinical utility in predicting poststroke functional recovery. We aimed to assess the value of serum biomarkers (C-reactive protein [CRP], D-dimer, fibrinogen, and S100ß protein) in predicting medium-term (12 weeks) functional outcome in patients with acute ischemic stroke. METHODS: This is an observational, prospective study in a sample of patients hospitalized for ischemic stroke (N = 131). Peripheral blood levels of biomarkers of interest were determined at admission (CRP, D-dimer, and fibrinogen) or at 48 hours poststroke (S100ß protein). Functional status was accessed at 48 hours and 12 weeks poststroke using the modified Rankin Scale (mRS). RESULTS: S100ß protein levels measured at 48 hours were significantly associated with mRS scores at 12 weeks (odds ratio = 1.005, 95% confidence interval [CI] [1.005-1.007]; P <.001). This association was not seen for the remaining biomarkers of interest. The S100ß cutoff for poor functionality at 12 weeks was 140.5 ng/L or more (sensibility 83.8%; specificity 71.4%; area under the curve = .80, 95% CI [.722, .879]). CONCLUSIONS: S100ß levels in peripheral blood at 48 hours poststroke reflect acute stroke severity and predict functional outcome at 12 weeks with a cutoff value of 140.5 ng/dL. The value of S100ß as predictor of functional recovery after stroke should be emphasized in further clinical research and clinical practice.

Cerebrovascular Dissemination in Time and Space as a Predictor of Cardioembolism.

BACKGROUND: Cardioembolism has tendency to recur and cause lesions in distinct cerebrovascular territories. Using the imaging characteristics of cerebral lesions to determine dissemination in time and space (DTS) is a concept already used in other neurologic conditions; however, it has never been applied as a diagnostic tool in ischemic stroke etiology. AIM: This study aimed to assess DTS as a diagnostic marker of cardioembolism. METHODS: We enrolled consecutive patients with acute ischemic stroke of various etiologies admitted in a cerebrovascular disease nursery from a university hospital in a retrospective cohort study. We excluded patients with coexisting etiologies, incomplete study, or without an acute vascular lesion on computed tomography scan. Lacunar infarctions were not considered. Cerebrovascular territory was divided into right anterior, left anterior, and posterior. Localization of the acute vascular lesion(s), existence of previous vascular lesions, and their respective areas were analyzed. The presence of dissemination in time, space, or DTS was determined. RESULTS: We included 661 patients (mean age: 74.05 years (SD: 13.01)). Cardioembolism was the etiology with most DTS (30.47% of cardioembolic strokes); DT occurred more frequently within the atherosclerotic subtype (9.88%); DS was more prevalent within the arterial dissection group (3.33%). There was a statistically significant difference in stroke etiology between patients with DTS and patients without dissemination (P < .001). DTS had 81.67% specificity, 30.47% sensitivity, 66.67% positive predictive value, and 49.40% negative predictive value for the identification of cardioembolism. CONCLUSION: DTS is a specific diagnostic predictor of cardioembolic stroke and may be helpful in guiding etiologic investigation.

CHADS(2) and CHA(2)DS(2)VASc scores as predictors of cardioembolic sources in secondary stroke prevention.

INTRODUCTION AND OBJECTIVES: Cardioembolism is one of the most common causes of ischemic stroke, with an estimated prevalence of 20-30%, and correct diagnosis is essential given the therapeutic implications. Although stroke risk scores (CHADS2 and more recently CHA2DS2-VASc) have been validated in heterogeneous populations of patients with atrial fibrillation, their accuracy has not been ascertained for secondary stroke prevention. We set out to assess the sensitivity and specificity of the CHADS2 and CHA2DS2-VASc stroke risk scores as predictors of cardioembolic sources, documented by transesophageal echocardiography (TEE) in a population with ischemic stroke. METHODS: The CHADS2 and CHA2DS2-VASc scores were applied to all patients admitted to the stroke unit/neurology ward of a Portuguese tertiary hospital with atrial fibrillation (diagnosed previously or during or after admission) who underwent TEE between January and August 2011. The presence of a cardioembolic source was defined as the observation by TEE of spontaneous echo contrast in the left atrium and atrial appendage or thrombi in the left cardiac chambers. RESULTS: We studied 94 patients, 66.0% male, mean age 64.4 years (standard deviation 14.2). A cardioembolic source was detected in 20 patients. ROC curve analysis identified as predictors of cardioembolic source CHADS2 score ≥4 (sensitivity of 75.0%, specificity of 66.0%, p=0.014) and CHA2DS2-VASc score ≥5 (sensitivity of 83.3%, specificity of 58.0%, p=0.009). CONCLUSIONS: Both scores showed acceptable sensitivity as predictors of embolic risk in the context of secondary prevention of cardioembolic stroke. The CHA2DS2-VASc score has higher sensitivity than CHADS2 but lower specificity.