SARS-CoV-2 infection and acute ischemic stroke in Lombardy, Italy.

OBJECTIVE: To characterize patients with acute ischemic stroke related to SARS-CoV-2 infection and assess the classification performance of clinical and laboratory parameters in predicting in-hospital outcome of these patients. METHODS: In the setting of the STROKOVID study including patients with acute ischemic stroke consecutively admitted to the ten hub hospitals in Lombardy, Italy, between March 8 and April 30, 2020, we compared clinical features of patients with confirmed infection and non-infected patients by logistic regression models and survival analysis. Then, we trained and tested a random forest (RF) binary classifier for the prediction of in-hospital death among patients with COVID-19. RESULTS: Among 1013 patients, 160 (15.8%) had SARS-CoV-2 infection. Male sex (OR 1.53; 95% CI 1.06-2.27) and atrial fibrillation (OR 1.60; 95% CI 1.05-2.43) were independently associated with COVID-19 status. Patients with COVID-19 had increased stroke severity at admission [median NIHSS score, 9 (25th to75th percentile, 13) vs 6 (25th to75th percentile, 9)] and increased risk of in-hospital death (38.1% deaths vs 7.2%; HR 3.30; 95% CI 2.17-5.02). The RF model based on six clinical and laboratory parameters exhibited high cross-validated classification accuracy (0.86) and precision (0.87), good recall (0.72) and F1-score (0.79) in predicting in-hospital death. CONCLUSIONS: Ischemic strokes in COVID-19 patients have distinctive risk factor profile and etiology, increased clinical severity and higher in-hospital mortality rate compared to non-COVID-19 patients. A simple model based on clinical and routine laboratory parameters may be useful in identifying ischemic stroke patients with SARS-CoV-2 infection who are unlikely to survive the acute phase.

Impact of SARS-CoV-2 on reperfusion therapies for acute ischemic stroke in Lombardy, Italy: the STROKOVID network.

Whether and how SARS-CoV-2 outbreak affected in-hospital acute stroke care system is still matter of debate. In the setting of the STROKOVID network, a collaborative project between the ten centers designed as hubs for the treatment of acute stroke during SARS-CoV-2 outbreak in Lombardy, Italy, we retrospectively compared clinical features and process measures of patients with confirmed infection (COVID-19) and non-infected patients (non-COVID-19) who underwent reperfusion therapies for acute ischemic stroke. Between March 8 and April 30, 2020, 296 consecutive patients [median age, 74 years (interquartile range (IQR), 62-80.75); males, 154 (52.0%); 34 (11.5%) COVID-19] qualified for the analysis. Time from symptoms onset to treatment was longer in the COVID-19 group [230 (IQR 200.5-270) minutes vs. 190 (IQR 150-245) minutes; p = 0.007], especially in the first half of the study period. Patients with COVID-19 who underwent endovascular thrombectomy had more frequently absent collaterals or collaterals filling ≤ 50% of the occluded territory (50.0% vs. 16.6%; OR 5.05; 95% CI 1.82-13.80) and a lower rate of good/complete recanalization of the primary arterial occlusive lesion (55.6% vs. 81.0%; OR 0.29; 95% CI 0.10-0.80). Post-procedural intracranial hemorrhages were more frequent (35.3% vs. 19.5%; OR 2.24; 95% CI 1.04-4.83) and outcome was worse among COVID-19 patients (in-hospital death, 38.2% vs. 8.8%; OR 6.43; 95% CI 2.85-14.50). Our findings showed longer delays in the intra-hospital management of acute ischemic stroke in COVID-19 patients, especially in the early phase of the outbreak, that likely impacted patients outcome and should be the target of future interventions.

Prion-related peripheral neuropathy in sporadic Creutzfeldt-Jakob disease.

OBJECTIVE: To assess whether the involvement of the peripheral nervous system (PNS) belongs to the phenotypic spectrum of sporadic Creutzfeldt-Jakob disease (sCJD). METHODS: We examined medical records of 117 sCJDVV2 (ataxic type), 65 sCJDMV2K (kuru-plaque type) and 121 sCJDMM(V)1 (myoclonic type) subjects for clinical symptoms, objective signs and neurophysiological data. We reviewed two diagnostic nerve biopsies and looked for abnormal prion protein (PrPSc) by western blotting and real-time quaking-induced conversion (RT-QuIC) in postmortem PNS samples from 14 subjects. RESULTS: Seventy-five (41.2%) VV2-MV2K patients, but only 11 (9.1%) MM(V)1, had symptoms or signs suggestive of PNS involvement occurring at onset in 18 cases (17 VV2-MV2K, 9.3%; and 1 MM(V)1, 0.8%) and isolated in 6. Nerve biopsy showed a mixed predominantly axonal and demyelinating neuropathy in two sCJDMV2K. Electromyography showed signs of neuropathy in half of the examined VV2-MV2K patients. Prion RT-QuIC was positive in all CJD PNS samples, whereas western blotting detected PrPSc in the sciatic nerve in one VV2 and one MV2K. CONCLUSIONS: Peripheral neuropathy, likely related to PrPSc deposition, belongs to the phenotypic spectrum of sCJDMV2K and VV2 and may mark the clinical onset. The significantly lower prevalence of PNS involvement in typical sCJDMM(V)1 suggests that the PNS tropism of sCJD prions is strain dependent.

Towards an early clinical diagnosis of sporadic CJD VV2 (ataxic type).

INTRODUCTION: Sporadic Creutzfeldt-Jakob disease (sCJD) includes a broad spectrum of clinical-pathological subtypes, which complicates the clinical differential diagnosis with other rapidly progressive neurological syndromes. AIM: To provide a better characterisation of clinical features and results of diagnostic investigations, especially at an early disease stage, in patients with sCJDVV2, the second most common sCJD subtype. METHODS: We evaluated neurological symptoms/signs, and results of brain diffusion-weighted resonance imaging (DW-MRI), electroencephalographic recordings (EEG) and cerebrospinal fluid (CSF) biomarker studies in 120 patients with a definite (n=93) or probable (n=27) diagnosis of sCJDVV2. RESULTS: All patients presented with prominent cerebellar signs, which were often associated with memory loss and/or oculomotor, visual or peripheral/spinal cord signs. In contrast, dementia was invariably a late finding. All CSF samples were positive for the 14-3-3 protein assay and had total-tau protein levels above 1250 pg/mL. Brain DW-MRI showed hyperintensity of basal ganglia, thalamus and cerebral cortex, respectively in 91.5%, 57.4% and 19.1% of cases. EEG revealed periodic sharp-wave complexes in only 17.8% of cases. CONCLUSIONS: sCJDVV2 should be considered in any patient presenting with a rapidly progressive ataxia, especially when associated with oculomotor, visual or peripheral/spinal cord signs, even in the absence of dementia or myoclonus. CSF assays and brain DW-MRI represent sensitive diagnostic tests, even at an early stage. These data strongly suggest that sCJDVV2 can be clinically diagnosed early and accurately based on clinical data, DW-MRI, CSF assays and codon 129 genotyping and provide the basis for improved and subtype-specific diagnostic criteria of sCJD.

Progressive supranuclear gaze palsy without parkinsonism: a case of neuro-Whipple.

We report the case of a 69-year-old man with a 7-month history of severe progressive supranuclear gaze palsy associated with mild cognitive decline and sleep disturbances, but not parkinsonism. After a period spent consulting a range of different specialists, the appearance of brachial myoclonus prompted his referral to a movement disorders specialist. Duodenum biopsy confirmed the suspicion of neuro-Whipple disease. Antibiotic therapy was started but the delay in the diagnosis proved fatal to this patient. This noteworthy case shows unusual neurological features of a rare but treatable disease, often misdiagnosed as progressive supranuclear palsy.

Time ordering in frontal lobe patients: a stochastic model approach.

Frontal lobe patients reproduced a sequence of capital letters or abstract shapes. Immediate and delayed reproduction trials allowed the analysis of short- and long-term memory for time order by means of suitable Markov chain stochastic models. Patients were as proficient as healthy subjects on the immediate reproduction trial, thus showing spared encoding and short-term memory. They failed, instead, on the delayed trials with capital letters, but not with random shapes, suggesting that their long-term memory impairment did not depend on primary deficits for ordering, but on inability to benefit from the organisational strategies that improve the retention and retrieval in normal subjects.