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Background: The benefit of distinguishing between disabling versus nondisabling deficit in mild acute ischemic stroke due to endovascular thrombectomy-targetable vessel occlusion (EVT-tVO; including anterior circulation large and medium-vessel occlusion) is unknown. We compared safety and efficacy of acute reperfusion treatments in disabling versus nondisabling mild EVT-tVO. Methods: From the Safe Implementation of Treatments in Stroke-International Stroke Thrombolysis Register, we included consecutive acute ischemic stroke patients (2015–2021) treated within 4.5 hours, with full NIHSS items availability and score ≤5, evidence of intracranial internal carotid artery, M1, A1-2, or M2-3 occlusion. After propensity score matching, we compared efficacy (3-month modified Rankin Scale score of 0–1, modified Rankin Scale score of 0–2, and early neurological improvement) and safety (nonhemorrhagic early neurological deterioration, any intracerebral or subarachnoid hemorrhage, symptomatic intracranial hemorrhage, and death at 3-month) outcomes in disabling versus nondisabling patients—adopting an available definition. Results: We included 1459 patients. Propensity score matched analysis of disabling versus nondisabling EVT-tVO (n=336 per group) found no significant differences in efficacy (modified Rankin Scale score 0–1: 67.4% versus 71.5%, P =0.336; modified Rankin Scale score 0–2: 77.1% versus 77.6%, P =0.895; early neurological improvement: 38.3% versus 44.4%, P =0.132) and safety (nonhemorrhagic early neurological deterioration: 8.5% versus 8.0%, P =0.830; any intracerebral hemorrhage or subarachnoid hemorrhage: 12.5% versus 13.3%, P =0.792; symptomatic intracranial hemorrhage: 2.6% versus 3.4%, P =0.598; and 3-month death: 9.8% versus 9.2%, P =0.844) outcomes. Conclusions: We found similar safety and efficacy outcomes after acute reperfusion treatment in disabling versus nondisabling mild EVT-tVO; our findings suggest to adopt similar acute treatment approaches in the 2 groups. Randomized data are needed to clarify the best reperfusion treatment in mild EVT-tVO.

Introduction: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a prothrombotic syndrome observed after adenoviral vector-based vaccines for severe acute respiratory syndrome coronavirus 2. It is characterized by thrombocytopenia, systemic activation of coagulation, extensive venous thrombosis, and anti-platelet factor 4 antibodies. Arterial thrombosis is less common and mainly affects the aorta, peripheral arteries, heart, and brain. Several cases of ischemic stroke have been reported in VITT, often associated with large vessel occlusion (LVO). Here, we describe a case of ischemic stroke with LVO after Ad26.COV2.S vaccine, then we systematically reviewed the published cases of ischemic stroke and VITT following COVID-19 vaccination. Methods: We describe a 58-year-old woman who developed a thrombotic thrombocytopenia syndrome with extensive splanchnic vein thrombosis and ischemic stroke due to right middle cerebral artery (MCA) occlusion, 13 days after receiving Ad26.COV2.S vaccination. Then, we performed a systematic review of the literature until December 3, 2021 using PubMed and EMBASE databases. The following keywords were used: (“COVID-19 vaccine”) AND (“stroke”), (“COVID-19 vaccine”) AND (“thrombotic thrombocytopenia”). We have selected all cases of ischemic stroke in VITT. Results: Our study included 24 patients. The majority of the patients were females (79.2%) and younger than 60 years of age (median age 45.5 years). Almost all patients (96%) received the first dose of an adenoviral vector-based vaccine. Ischemic stroke was the presenting symptom in 18 patients (75%). Splanchnic venous thrombosis was found in 10 patients, and cerebral venous thrombosis in 5 patients (21%). Most patients (87.5%) had an anterior circulation stroke, mainly involving MCA. Seventeen patients (71%) had an intracranial LVO. We found a high prevalence of large intraluminal thrombi (7 patients) and free-floating thrombus (3 patients) in extracranial vessels, such as the carotid artery, in the absence of underlying atherosclerotic disease. Acute reperfusion therapy was performed in 7 of the 17 patients with LVO (41%). One patient with a normal platelet count underwent intravenous thrombolysis with alteplase, while 6 patients underwent mechanical thrombectomy. A malignant infarct occurred in 9 patients and decompressive hemicraniectomy was performed in 7 patients. Five patients died (21%). Conclusion: Our study points out that, in addition to cerebral venous thrombosis, adenoviral vector-based vaccines also appear to have a cerebral arterial thrombotic risk, and clinicians should be aware that ischemic stroke with LVO, although rare, could represent a clinical presentation of VITT.

The authors will present a comprehensive account of the neurological aspects of SARS-CoV-2 infection. The aim is to provide a practical clinical book which will serve as a guide for clinicians from all specialties involved in the management of COVID-19 patients. The authors share the extensive clinical experience gained in major hospitals in Lombardy, the first European region to face the COVID-19 emergency in 2020. All are recognized international experts in their respective fields and have been involved in the management of COVID-19 cases from the very beginning of the Italian SARS-CoV-2 outbreak. The text begins with a description of pathobiological and pathophysiological aspects related to the involvement of the nervous system, moving on to the discussion of the neurological complications observed in COVID-19 patients; these range from central to peripheral symptoms, and can occur in the acute or post-acute phases of the disease. Further topics are: neuropathology, seizures and EEG, neuroimaging, delirium, encephalomyelitis, stroke, psychopathology and psychiatry, neuropsychology and cognitive impairment, neuromuscu-lar disorders, and the impact of COVID-19 on other pre-existing neurological disorders. In addi-tion, the book will discuss the new developments in teleneurology approaches, which have been a direct response to the ongoing pandemic. Finally, the possible neurological complications of the COVID-19 vaccines and the neurological complications in children will be considered.Each chapter will present a critical review of the existing literature concerning the specific subject matter, followed by practical clinical recommendations, as well as personal considerations based on the experience gained by each author during the course of the COVID-19 pandemic.Neurology of COVID-19 will be an original and innovative reference book for clinicians of all the specialties involved in the management of patients with SARS-CoV-2 infection. ________________________________________________ List of chapters ________________________________________________

To identify the clinical profile and aura characteristics of patients with Migraine with Aura (MwA) having acute cerebral ischemia, we compared stroke phenotype and risk factors in stroke patients with (S+MwA+) or without (S+MwA−) MwA and aura features in MwA patients with (S+MwA+) or without (S−MwA+) stroke. In this retrospective multicenter case–control study, we reviewed stroke phenotypes and vascular risk factors in S+MwA+ and S+MwA− patients younger than 60 years and risk factors and aura type, duration, onset age, and the frequency in the previous year in S+MwA+ patients and S−MwA+ subjects matched for age and disease history, investigated for patent foramen ovale (PFO). 539 stroke (7.7% S+MwA+) and 94 S−MwA + patients were enrolled. S+MwA+ patients were younger (p =.0.004) and more frequently presented PFO [OR 4.89 (95% CI 2.12–11.27)], septal interatrial aneurism [OR 2.69 (95% CI 1.15–6.27)] and cryptogenic ischemic stroke (CIS) [OR 6.80 (95% CI 3.26–14.18)] than S+MwA− subjects. Significant atherosclerosis was not detected in S+MwA+ patients. Compared to S−MwA+, S+MwA+ patients were characterized by visual [OR 3.82 (95% CI 1.36–10.66)] and shorter-lasting (20.0 min IQr 13.1 vs 30.0 min IQr 25.0; p

A 61-year-old White man with hypertension and diabetes presented to the emergency department with a 10-day history of excessive daytime sleepiness, confusion, mental slowing, memory loss, and behavioral changes. He had become apathetic and quieter with loss of initiative and showed reduction of spontaneous speech. No headache, fever, or recent infections were reported. Neurologic examination revealed hypomimia, mild parkinsonism (mild rigidity of the left arm, reduced bilateral arm swing during gait, global mild bradykinesia), confusion with partial disorientation in time and space, and short- and long-term memory impairment. Mini-Mental State Examination Scale score was 15. Cranial nerves, speech, language, motor, sensory, and cerebellar functions and reflexes were normal. Brain CT scan and arterial and venous CT angiography (CTA) were normal. The patient was admitted to our neurologic department for further management.

Background: The causal relationship between patent foramen ovale (PFO) and migraine with aura (MA) is controversial. We aimed at exploring whether attack clinical features relate to the presence of right-to-left shunt (RLS) in MA patients. Methods: We retrospectively examined a cohort of consecutive patients diagnosed with MA in our headache center and undergoing transcranial doppler (TCD) for RLS detection. We collected from our clinical electronic dossiers, clinical features of MA attacks (type, frequency, duration of aura phenomenon, trigger factors, onset age), family history for MA, thrombophilia genotypes, and the response to preventive treatments. RLS was stratified for severity according to the results of the TCD examination. Results: We found 111 patients. Binary logistic regression analysis showed that among features of MA attacks, only onset age was associated with the presence of RLS (p < 0.0001). Patients with RLS presented the first MA attack at a younger age (p < 0.0001). The greater RLS severity, the younger was onset age (p < 0.00001) and the presence of atrial septal aneurysms (ASA) was associated with a further decrease in onset age (ρ = –539, p < 0.00001). Family history for MA was associated with the presence of RLS (chi-square p = 0.022). Response to preventive treatments was not influenced by the type of treatment (antiplatelet compared with no antiplatelet drugs), comorbidity with migraine without aura, RLS presence, or by their double interactions (Logistic regression, consistently p > 0.05). Conclusion: Our findings support the hypothesis that although PFO does not influence MA attack frequency, it is not merely a bystander in MA physiopathology, as RLS, its severity, and the presence of ASA possibly make a difference in the disease history.

Patent Foramen Ovale and impaired cerebral hemodynamics were proposed among the pathophysiological mechanisms explaining the increased risk for stroke in patients with Migraine with Aura (MA). Our study aimed at comparing the vasomotor reactivity (VMR) of the anterior and the posterior cerebral circulation in patients with Migraine with Aura, in patients with acute vascular ischemic accidents, and in controls. We hypothesized that VMR in MA patients is preserved in the anterior circulation and reduced in the posterior circulation. We prospectively assessed with Transcranial Doppler the vasomotor reactivity to breath holding of the Middle and Posterior Cerebral Arteries (MCA, PCA) in MA patients, in acute vascular patients and healthy controls. We also evaluated the possible effect of clinical characteristics of MA (attack frequency, aura length or type, disease history), vascular factors and the presence of right-to-left shunt on VMR. Diverging from our hypothesis, MA patients displayed a higher breath-holding index (BHI) than controls in the MCA (1.84±0.47%/s vs 1.53±0.47%/s, p = .001) as well as in the PCA (1.87±0.65%/s vs 1.47±0.44%/s, p < .001). In MA patients, MCA BHI was higher in those with large right-to-left shunts (2.09±0.42 vs 1.79±0.47, p = .046) and lower in those taking estrogens (1.30±0.30%/s vs 1.9±0.45%/s, p = .009). We did not observe an effect of MA characteristics on BHI. The increased BHI in MA patients with large right-to-left shunts could be explained by the vasoactive effect in the cerebral circulation of substances bypassing the deactivating pulmonary filters or by a constitutional trait of the vascular system associating persistent right-to-left shunts and hyper-reactive hemodynamics. Our results discourage the hypothesis that altered hemodynamics contribute to increasing the stroke risk in all MA patients. However, estrogens can lower VMR, curtailing the hemodynamic resources of MA patients.

This work proposes a broad analysis for the de-tection of the most relevant features for the sit-to-stand task analysis, in Parkinson's disease (PD) patients and healthysubjects (H). A group of sixteen PD patients and thirteen H subjects have been analyzed, using one magneto-inertial sensor, while the physician administers the UPDRS clinical scale. The PD group has been examined before and after thepharmacological therapy (respectively, OFF and ON phase), in order to monitor the different states of the PD, which implies changes in motor control. By calculating the features of this task, it has been possible to choose the most reliable indexes, already used in this task in order to identify differences in the score assigned through sensors. In addition to that, it has also been possible to find differences in the features' values which the clinical scale and the physician cannotidentify. Our study highlights how wearable motion sensors can detect statistically significant differences between OFF/ON phase and H subjects that the clinical evaluation can not. We conclude that our method provides a deep analysis of the sit-to-stand task with only one M-IMU, allowing to check PD patient status,providing a method for home care monitoring.

Daith piercing is an ear piercing located at the crus of the helix, bilaterally. It is getting great consent on social media as alternative treatment in chronic migraine. No data about its efficacy and action are available in scientific literature so far. We present the case of a 54-year-old male patient suffering from refractory chronic migraine with medication-overuse, who substantially improved after bilateral ear daith piercing. His migraine was refractory to symptomatic as well as prophylactic therapies. He used to treat headaches with up to five symptomatic drugs per attack and had attempted several pharmacological preventive therapies, including Onabotulinumtoxin A. He also underwent detoxification treatments with intravenous steroids and diazepam, without durable benefit. At the time of daith piercing, the headache-related disability measures showed a HIT-6 score of 64, a MIDAS-score of 70, and a 11-point Box scale of 5. On his own free will, he decided to get a “daith piercing.” After that, he experienced a reduction of migraine attacks, which became very rare, and infrequent, less disabling episodes of tension-type headache (HIT-6 score of 56; MIDAS score of 27, 11-point Box scale of 3). Painkiller assumption has much decreased: he takes only one tablet of indomethacin 50 mg to treat tensive headaches, about four times per month. Beyond a placebo effect, we can speculate a vagal modulation as the action mechanism of daith piercing: a nociceptive sensory stimulus applied to trigeminal and vagal areas of the ear can activate ear vagal afferents, which can modulate pain pathways by means of projections to the caudal trigeminal nucleus, to the locus coeruleus and to the nucleus raphe magnus. Currently, daith piercing cannot be recommended as migraine treatment because of the lack of scientific evidence, the unquantified rate of failure and the associated risks with insertion. However, given the increasing but anecdotal evidence, we think that the mechanism needs testing by means of a controlled clinical trial in a population of chronic migraineurs.

Management of medication overuse headache (MOH) requires abrupt suspension of overused drugs either alone or in association with a detoxification protocol to prevent withdrawal. However, there is no consensus about which suspension strategy is the most effective. Moreover, reliable data about the possible mid-term effect of detoxification are not available. The objective of this study was to evaluate whether a bridge therapy consisting of a 5-day i.v. infusion of methylprednisolone and diazepam determines a significant reduction in headache frequency and drug assumption during the detoxification protocol (day 5) and in the first 3 months in patients with MOH. We conducted a retrospective non-randomized before-and-after study comparing patients with MOH undergoing a bridge therapy protocol (5-day infusion of methylprednisolone, diazepam) with those who refused the treatment and were only recommended to suspend overused painkillers. Both groups started a prophylactic treatment and were followed-up for 3 months. At day 5, 82% of our patients were headache-free; moreover, 48% of the patients did not take any painkiller during the 5-day treatment. Three months after, the intervention group showed a greater reduction of monthly headache days (9.4 vs 3.0) and drugs (19.7 vs 6.5), a greater rate of patients with a ≥ 50% reduction of monthly headaches (p = 0.019) and symptomatic drug consumption (p = 0.000), than the control group. The methylprednisolone and diazepam detoxification protocol reduced headache attacks and drug assumption immediately and in the first 3 months after the intervention, concurring to improve the effect of a new prophylactic therapy.