Sex differences in ischemic stroke during COVID-19 first outbreak in northern Italy.

INTRODUCTION: COVID-19 pandemic had a great impact on outcome in SARS-CoV-2 positive patients with ischemic stroke during the first wave in Italy. Few data are available on outcome stratified by sex. METHODS: The Italian Society of Hospital Neuroscience conducted a multi-center, retrospective, observational study on neurological complications in COVID-19 patients with ischemic stroke. All the patients admitted from March 1st to April 30th, 2020 in 20 Neurology Units in Northern Italy were recruited. Demographical and clinical features, treatment and outcome data were compared focusing on sex differences. RESULTS: 812 patients with ischemic stroke were enrolled, of whom 129 with COVID-19; males were 53.8%. In-hospital mortality in COVID-19 patients was 35.3% in males and 27.9% in females while 8.5% in male and 5.8% in female patients without COVID-19. SARS-CoV-2 positive patients had a higher frequency of stroke of undetermined etiology, than negative ones (32.8% vs 22.5%; p = 0.02), especially in females compared to males (36.1% vs 27.9%), albeit without statistical significance. Male patients with SARS-CoV-2 were more likely to require cPAP (30.9% vs 14.8%; p = 0.03), endotracheal tube (14.9% vs 3.3%; p = 0.02) and reperfusion strategies (29.4% vs 11.5%; p = 0.01) than females, as well as to have a higher CRP and D-dimer. These elements together with older age, a total anterior circulation stroke and lymphopenia were predictors of a worse outcome. DISCUSSION: Our study detected some differences due to sex in ischemic stroke with and without COVID-19, supporting the possibility to perform sex analyses for SARS-CoV-2 positive patients for a better clinical management.

Progressive motor neuron syndromes with single CNS lesions and CSF oligoclonal bands: never forget solitary sclerosis!

We describe 3 cases of solitary sclerosis (SS), a rare condition characterized by a single inflammatory demyelinating lesion in the white matter of the brain or spinal cord. All patients had progressive limb motor impairment (patient 1, 66-year-old female: left spastic hemiparesis; patient 2, 39-year-old male: right spastic hemiparesis; patient 3, 42-year-old female: proximally predominant left upper limb weakness with amyotrophy and fasciculations). In all patients, MRI disclosed a single small T2-hyperintense demyelinating lesion: in the right anterior paramedian upper medulla, in the median-left paramedian anterior lower medulla, and in the left paramedian anterior cervical spinal cord at C4 level, respectively. In patients 1 and 2, transcranial magnetic stimulation (TMS) demonstrated altered motor evoked potentials (MEPs) and increased central motor conduction time (CMCT) in the affected limbs; in patient 3, needle EMG revealed chronic neurogenic changes in C5-C7 muscles of left upper limb. Patients 1 and 2 had normal brain 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). CSF analysis demonstrated IgG oligoclonal bands in all patients. In patients 2 and 3, levels of neurofilament light chain (NFL) in CSF and serum, respectively, were within normal limits. The three cases were consistent with the diagnosis of SS. Notably, while the first two cases mimicked Mills' syndrome (the hemiparetic variant of primary lateral sclerosis, PLS), the third one was rather reminiscent of amyotrophic lateral sclerosis (ALS). This suggests including SS in the differential diagnosis not only of PLS, but also of ALS. We also report the first quantification of NFL levels in SS.

Subclinical Vascular Brain Lesions in Young Adults With Acute Ischemic Stroke.

BACKGROUND: Subclinical vascular brain lesions are highly prevalent in elderly patients with stroke. Little is known about predisposing factors and their impact on long-term outcome of patients with stroke at a young age. METHODS: We quantified magnetic resonance-defined subclinical vascular brain lesions, including lacunes and white matter hyperintensities, perivascular spaces and cerebral microbleeds, and assessed total small-vessel disease (SVD) score in patients with first-ever acute ischemic stroke aged 18 to 45 years, and followed them up, as part of the multicentre Italian Project on Stroke in Young Adults. The primary end point was a composite of ischemic stroke, transient ischemic attack, myocardial infarction, or other arterial events. We assessed the predictive accuracy of magnetic resonance features and whether the addition of these markers improves outcome prediction over a validated clinical tool, such as the Italian Project on Stroke in Young Adults score. RESULTS: Among 591 patients (males, 53.8%; mean age, 37.5±6.4 years), 117 (19.8%) had subclinical vascular brain lesions. Family history of stroke was associated with lacunes (odds ratio, 2.24 [95% CI, 1.30-3.84]) and total SVD score (odds ratio, 2.06 [95% CI, 1.20-3.53] for score≥1), hypertension with white matter hyperintensities (odds ratio, 2.29 [95% CI, 1.22-4.32]). After a median follow-up of 36.0 months (25th-75th percentile, 38.0), lacunes and total SVD score were associated with primary end point (hazard ratio, 2.13 [95% CI, 1.17-3.90] for lacunes; hazard ratio, 2.17 [95% CI, 1.20-3.90] for total SVD score ≥1), and the secondary end point brain ischemia (hazard ratio, 2.55 [95% CI, 1.36-4.75] for lacunes; hazard ratio, 2.61 [95% CI, 1.42-4.80] for total SVD score ≥1). The predictive performances of the models, including magnetic resonance features were comparable to those of the random model. Adding individual magnetic resonance features to the Italian Project on Stroke in Young Adults score did not improve model prediction. CONCLUSIONS: Subclinical vascular brain lesions affect ≈2 in 10 young adults with ischemic stroke. Although lacunes and total SVD score are associated with thrombotic recurrence, they do not improve accuracy of outcome prediction over validated clinical predictors.

Impact of SARS-CoV-2 infection on acute intracerebral haemorrhage in northern Italy.

INTRODUCTION: Growing evidence has been published as to the impact of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) on cerebrovascular events over the last few months, with considerable attention paid to ischemic strokes. Conversely, little is known about the clinical course of intracerebral haemorrhage (ICH) and simultaneous SARS-CoV-2 infection. METHOD: The Italian Society of Hospital Neurosciences (SNO) promoted a multicentre, retrospective, observational study (SNO-COVID-19), involving 20 Neurological Departments in Northern Italy. Clinical data on patients with acute cerebrovascular diseases, admitted from March 1st to April 30th, 2020, were collected. A comparison was made of the demographical and clinical features of both SARS-CoV-2 positive and negative patients with ICH. RESULTS: 949 patients were enrolled (average age 73.4 years; 52.7% males); 135 patients had haemorrhagic stroke and 127 (13.4%) had a primary ICH. Only 16 patients with ICH (12.6%) had laboratory confirmed SARS-CoV-2 infection, both symptomatic and asymptomatic. SARS-CoV-2 related pneumonia or respiratory distress (OR 5.4), lobar location (OR 5.0) and previous antiplatelet or anticoagulant treatment (OR 2.9) were the only factors significantly associated with increased mortality in ICH. SARS-CoV-2 infection, regardless of respiratory involvement, led to a non-significantly increased risk of in-hospital death (37.5% vs 23.4%, p = 0.2). DISCUSSION: ICH patients with COVID-19 did not experience an increase in mortality as striking as ischemic stroke. The inflammatory response and respiratory complications could justify the slight increase of death in ICH. Bleeding sites and previous antiplatelet or anticoagulant treatment were the only other predictors of a worse outcome.

Posterior reversible encephalopathy syndrome and COVID-19: A series of 6 cases from Lombardy, Italy.

Posterior reversible encephalopathy cases are increasingly being reported in patients affected by COVID-19, but the largest series so far only includes 4 patients. We present a series of 6 patients diagnosed with PRES during COVID-19 hospitalized in 5 Centers in Lombardia, Italy. 5 out of the 6 patients required intensive care assistence and seizures developed at weaning from assisted ventilation. 3 out of 6 patients underwent cerebrospinal fluid analysis which was normal in all cases, with negative PCR for Sars-CoV-2 genome search. PRES occurrence may be less rare than supposed in COVID-19 patients and a high suspicion index is warranted for prompt diagnosis and treatment.

Neuropsychological assessment in acute stroke patients.

BACKGROUND AND PURPOSE: The number of people suffering from stroke is strongly increasing, giving rise to multiple cognitive deficits which frequently prevent a full recovery. The identification of both spared and impaired cognitive domains has a key role to plan adequate interventions. However, the existing standard tests are either too expensive in terms of time and efforts for patients in acute stage or they derived from instruments addressing different pathologies such as dementia. METHODS: We developed a brief neuropsychological battery (mental performance in acute stroke, MEPS) to assess different cognitive domains (language, memory, praxis, visual perception) in acute stroke patients. MEPS was validated by enrolling a sample of 204 patients suffering from stroke in acute stage, and 263 healthy controls participants. RESULTS: The results indicated an adequate construct validity and a high ability in discriminating patients from healthy controls. CONCLUSIONS: MEPS can be considered a simple and highly valuable bedside battery, easy to administer, with values of sensitivity and specificity suitable to be proposed as a screening tool for patients with acute stroke.

History of Migraine and Volume of Brain Infarcts: The Italian Project on Stroke at Young Age (IPSYS).

Background and PURPOSE: Migraine has been shown to increase cerebral excitability, promote rapid infarct expansion into tissue with perfusion deficits, and result in larger infarcts in animal models of focal cerebral ischemia. Whether these effects occur in humans has never been properly investigated. METHODS: In a series of consecutive patients with acute ischemic stroke, enrolled in the setting of the Italian Project on Stroke at Young Age, we assessed acute as well as chronic infarct volumes by volumetric magnetic resonance imaging, and compared these among different subgroups identified by migraine status. RESULTS: A cohort of 591 patients (male, 53.8%; mean age, 37.5±6.4 years) qualified for the analysis. Migraineurs had larger acute infarcts than non-migraineurs (median, 5.9 cm3 [interquartile range (IQR), 1.4 to 15.5] vs. 2.6 cm3 [IQR, 0.8 to 10.1], P<0.001), and the largest volumes were observed in patients with migraine with aura (median, 9.0 cm3 [IQR, 3.4 to 16.6]). In a linear regression model, migraine was an independent predictor of increased log (acute infarct volumes) (median ratio [MR], 1.64; 95% confidence interval [CI], 1.22 to 2.20), an effect that was more prominent for migraine with aura (MR, 2.92; 95% CI, 1.88 to 4.54). CONCLUSION: s These findings reinforce the experimental observation of larger acute cerebral infarcts in migraineurs, extend animal data to human disease, and support the hypothesis of increased vulnerability to ischemic brain injury in people suffering migraine.

Persistent Interictal Musical Hallucination in a Patient With Mesial Temporal Sclerosis-Related Epilepsy: First Case Report and Etiopathological Hypothesis.

Musical hallucination is a disorder of complex sound processing of instrumental music, songs, choirs, chants, etc. The underlying pathologies include moderate to severe acquired hearing loss (the auditory equivalent of Charles Bonnet syndrome), psychiatric illnesses (depression, schizophrenia), drug intoxication (benzodiazepines, salicylate, pentoxifylline, propranolol), traumatic lesions along the acoustic pathways, and epilepsy. The hallucinations are most likely to begin late in life; 70% of patients are women. Musical hallucination has no known specific therapy. Treating the underlying cause is the most effective approach; neuroleptic and antidepressant medications have only rarely succeeded.Musical hallucination in epilepsy typically presents as simple partial seizures originating in the lateral temporal cortex. To our knowledge, no formal report of musical hallucination in the interictal state has been published before. In contrast, other interictal psychotic features are a relatively common complication, especially in patients with long-standing drug-resistant epilepsy.We describe a 62-year-old woman with a long history of mesial temporal lobe epilepsy whose musical hallucination was solely interictal. We speculate on the possible link between temporal epilepsy and her hallucination. We hypothesize that, as a result of her epileptic activity-induced damage, an imbalance developed between the excitatory and inhibitory projections connecting the mesial temporal cortex to the other auditory structures. These structures may have generated hyperactivity in the lateral temporal cortex through a "release" mechanism that eventually resulted in musical hallucination.

Prevalence of previously undiagnosed abdominal aortic aneurysms in the area of Como: the ComoCuore "looking for AAA" ultrasonography screening.

The prognosis for abdominal aortic aneurysm (AAA) rupture is poor. Long-term follow-up of population-based randomized trials has demonstrated that ultrasound (US) screening for abdominal aortic aneurysms (AAAs) measuring 3 cm or greater decreases AAA-related mortality rates and is cost-effective. We though to prospectively perform during a 26-month period a limited US examination of the infrarenal aorta in volunteers of both gender aged 60-85 years without history of AAA living in the area of Como, Italy. From September 2010 to November 2013 ComoCuore, a no-profit nongovernmental association, enrolled 1555 people (aged 68.8 ± 6.8 years; 48.6 % males). Clinical data and a US imaging of the aorta were collected for each participant. AAA was found in 22 volunteers (1.4 %) mainly males (2.5 % in males vs. 0.4 % in females p = 0.005). Overall, the prevalence of cardiovascular risk factors was higher in patients with vs. without AAA (mean 2.9 ± 3.0 vs. 1.4 ± 1.0 respectively, p < 0.0001). Independent predictors of AAA on multivariate analysis were age (OR 1.14, 1.06-1.22; p < 0.0001), male gender (OR 8.23, 1.79-37.91; p = 0.007), and both current (OR 4.98, 1.57-15.79; p = 0.007) and previous smoking (OR 2.76, 1.12-8.94; p = 0.03). Our study confirms the feasibility of one time US screening for AAA in a large cohort of asymptomatic people. Independent predictors of AAA were male sex, older age and a history of smoking. Accordingly to recent data the prevalence of AAA seems to be declining, maybe due to a reduction of smoking in Italy.

A practical definition of minor stroke.

It is generally assumed that minor stroke (MS) is an ischemic stroke with a short-term, good functional outcome. However, no clear definition of MS exists. Modified Rankin Scale (mRS) and National Institute of Health Stroke Scale (NIHSS) are still the most accredited standards, but scores and timing of the assessment are not homogeneous. As suggested by a qualified sample of Italian neurologists, the index parameter chosen in our analysis was mRS at the time of hospital discharge. The database of the SIRIO study (a large observational study of 2,573 patients with stroke admitted in Italian hospitals in 2005) was used to identify an mRS threshold to define MS. Reference was made to outcome markers such as rate of discharge to home, 1-year disability and 1-year mortality. The rate of discharge progressively decreased with increase in mRS, while the rates of 1-year mortality and disability progressively increased. Our proposal is one of defining a stroke "minor" when the rate of discharge to home is above the SIRIO database overall value and the 1-year mortality and disability is below the respective overall values. This definition is consistent with a score ≤2 on the mRS.

Cardiopulmonary resuscitation training in high-school adolescents by distributing personal manikins. The Como-Cuore experience in the area of Como, Italy.

BACKGROUND: Most witnessed out-of-hospital cardiac arrests (OHCA) do not receive bystander cardiopulmonary resuscitation (CPR). The incidence of laypersonsO' CPR could be increased by widespread training. We evaluated the effect of distribution of CPR educational material to high-school students in the area of Como, Italy. METHODS AND RESULTS: From January 2008 to October 2009, we distributed 3200 resuscitation manikins to pupils (62% boys, mean age 16.5 ± 0.8 years) at 20 high schools in the area of Como. All students received a kit including a personal manikin and a 27 min educational digital video disc. Furthermore, they received 40 min school training in the fundamental maneuvers of CPR utilizing the manikin. Afterwards, they were encouraged to train friends and relatives at home (second tier), utilizing the kit. Eight months later, a questionnaire was randomly submitted to a sample of 600 students (19% of the distributed manikins). The 600 kits had been used to train 1058 from the second tier (mean, 1.77 persons per pupil; 95% confidence interval 1.62-1.93). Boys had a significantly lower multiplier effect than girls: 1.45 ± 1.01 vs. 2.26 ± 1.89 (P < 0.0001). Ninety-five percent of pupils considered themselves sufficiently trained in CPR and 62.3% declared their availability to effectively practice CPR if necessary. One pupil performed an effective CPR during her mother's OHCA. CONCLUSIONS: CPR training can be disseminated using personal manikins distributed to pupils. Most students declared themselves trained and willing to start bystander CPR if necessary. One successful CPR was effectively performed.

Agenesis of the right internal carotid artery and Klippel-Feil syndrome: case report.

STUDY DESIGN: Case report. OBJECTIVE: To describe the case of a Klippel-Feil anomaly associated with carotid agenesis. SUMMARY OF BACKGROUND DATA: Klippel-Feil anomaly is a spinal malformation characterized by fusion of the cervical vertebrae. Four subtypes have been identified for this congenital disorder with different severity of vertebral fusion and different extra-axial anomalies. Most cases are sporadic, although autosomal dominant and autosomal recessive cases are recognized. It can cause neurologic disorders and is associated to vascular abnormalities. However, agenesis of internal carotid and Klippel-Feil syndrome is an unusual association. METHODS: A 49-year-old woman came to our attention for recurrent transitory ischemic attacks presenting with weakness of left limbs associated with sensory abnormalities. Neurologic examination revealed mild left limb weakness and tactile hypoesthesia. RESULTS: Brain magnetic resonance (MR) and MR angiography demonstrated absence of the right internal carotid and the middle right cerebral artery was filled from the basilar artery. Fusion of vertebral bodies was documented at MR and confirmed at spinal CT scan. The day after the admission the neurologic examination became normal. Ticlopidine was then started. CONCLUSION: Literature of vascular abnormalities in association with Klippel-Feil syndrome takes the form of anecdotal reports. Aortic coarctation, vertebral artery dissection, aneurysms, persistent trigeminal artery, and abnormal origin of internal carotid are described. An unusual association of carotid internal agenesis and Klippel-Feil syndrome is reported with a literature review.

Different types of chronic inflammatory demyelinating polyneuropathy have a different clinical course and response to treatment.

Chronic inflammatory demyelinating polyneuropathy (CIDP) can occur in association with other systemic diseases such as diabetes mellitus (DM) and IgG or IgA monoclonal gammopathy of undetermined significance (MGUS). Whether CIDP that is idiopathic (I-CIDP) or associated with diabetes (CIDP-DM) or MGUS (CIDP-MGUS) differ in clinical presentation, laboratory features, response to treatment, and long-term outcome is unclear, as is the relationship between these coexisting diseases and CIDP. In order to clarify this issue, we began a prospective follow-up study. Thirty-one consecutive patients with untreated CIDP, fulfilling the most restrictive diagnostic criteria, were enrolled over 18 months. Among the patients, 16 were diabetic, 7 had a MGUS, and 8 had an idiopathic CIDP. All patients were treated with IVIg, and the responders were treated again if they relapsed. In all three groups, improvement occurred after treatment. At the end of the follow-up, there was no difference in clinical conditions between groups, but a significant difference existed in the number of relapses and of IVIg administrations. CIDP-DM is a more severe disease, but with a significantly better response to IVIg and fewer relapses, than the other types that we studied.

Prognostic value of electrocardiograms, ventricular late potentials, ventricular arrhythmias, and left ventricular systolic dysfunction in patients with Duchenne muscular dystrophy.

Myocardial involvement is a common finding in patients with Duchenne-type muscular dystrophy (DMD). Nevertheless, the prognostic values of standard electrocardiogram (ECG), ventricular arrhythmias, ventricular late potentials (LPs), and left ventricular (LV) systolic dysfunction have not been extensively investigated. Eighty-four patients with DMD (aged 18.6 +/- 4.8 years) underwent standard and signal-averaged electrocardiography, 24-hour Holter monitoring, and echocardiography. The prevalence of electrocardiographic abnormalities, frequent ventricular premature complexes, LPs, and LV systolic dysfunction was 71%, 32%, 28%, and 35%, respectively. Median follow-up was 76 months (range 5 to 106). The mortality rate in the follow-up period was 27%. The typical DMD electrocardiographic alterations, ventricular arrhythmic pattern, and LPs were not predictors of mortality. In contrast, the presence of LV systolic dysfunction detected on echocardiography was a powerful predictor of mortality in the follow-up period (p = 0.013, hazard ratio 3.14, 95% confidence interval 1.27 to 7.79). Thus, echocardiographic assessment of LV systolic dysfunction provides prognostic information in patients with DMD. Electrocardiographic alterations, ventricular arrhythmias, and LPs have no prognostic value in predicting mortality in these patients.