Giovanni Malferrari

Cerebral stroke injury: the role of cytokines and brain inflammation.

Abstract Stroke represents the most frequent cause of permanent disability in adults worldwide. Cerebral ischemia triggers the pathological pathways of the ischemic cascade and causes irreversible neuronal injury in the ischemic core within minutes of the onset. Elements of the immune system are involved in all stages of ischemic cascade from acute intravascular events triggered by the interruption of blood supply, to the parenchymal processes leading to brain damage and to the ensuing tissue repair. In this review, we will provide a brief overview of current understanding of the role of cytokines and brain inflammation during acute ischemic stroke.

Observational case-control study of the prevalence of chronic cerebrospinal venous insufficiency in multiple sclerosis: Results from the CoSMo study

Background: Chronic cerebrospinal venous insufficiency (CCSVI) has been proposed as a possible cause of multiple sclerosis (MS). Objectives: The CoSMo study evaluated the association between CCSVI and MS. Methods: The primary end-point of this multicentric, case-control study was to compare the prevalence of CCSVI between patients with MS, patients with other neurodegenerative diseases (ONDs) and healthy controls (HCs). Color-coded duplex sonography was performed by a sonologist and the images were sent to one of three central sonologists for a second reading. Agreement between local and central sonologists or, in case of disagreement, the predominant judgment among the three central readers, was required for a diagnosis of CCSVI. All readings, data collection and analysis were blinded. Results: The study involved 35 MS centers across Italy and included 1874 subjects aged 18–55. 1767 (94%) were evaluable: 1165 MS patients, 226 patients with ONDs and 376 HCs. CCSVI prevalence was 3.26%, 3.10% and 2.13% for the MS, OND and HC groups, respectively. No significant difference in CCSVI prevalence was found amongst the three cohorts (MS versus HC, OR = 1.55, 95%CI = 0.72–3.36, p = 0.30; OND versus HC, OR = 1.47, 95%CI = 0.53–4.11, p = 0.46; MS versus OND, OR = 1.05, 95%CI = 0.47–2.39, p = 0.99). High negative and low positive agreement was found between the local and centralized readers. Conclusions: CCSVI is not associated with MS.

Antiepileptic drugs for central post-stroke pain management.

Antiepileptic drugs (AEDs) are commonly prescribed for a wide range of disorders other than epilepsy, including both neurological and psychiatric disorders. AEDs play also a role in pharmacological management of neuropathic pain. Central post-stroke pain (CPSP) is a disabling morbidity occurring in 35% of patients with stroke. The pathophysiology of CPSP is not well known but central disinhibition with increased neuronal excitability has been suggested. AEDs include many different drugs acting on pain through several mechanisms, such as reduction of neuronal hyperexcitability. To our knowledge conclusive evidence has not been published yet. The aim of this review is to delineate efficacy and safety of AEDs in CPSP.

Post-stroke Movement Disorders: Clinical Manifestations and Pharmacological Management

Involuntary abnormal movements have been reported after ischaemic and haemorrhagic stroke. Post stroke movement disorders can appear as acute or delayed sequel. At the moment, for many of these disorders the knowledge of pharmacological treatment is still inadequate. Dopaminergic and GABAergic systems may be mainly involved in post-stroke movement disorders. This article provides a review on drugs commonly used in post-stroke movement disorders, given that some post-stroke movement disorders have shown a partial benefit with pharmacological approach.

Italian multicentre observational study of the prevalence of CCSVI in multiple sclerosis (CoSMo study): Rationale, design, and methodology

Chronic cerebro-spinal venous insufficiency (CCSVI) has been proposed as a “congenital malformation” implicated in the pathogenesis of multiple sclerosis (MS). However, numerous studies failed to confirm its presence in MS patients. This paper presents the rationale, design, and methodology adopted in the CoSMo study, conducted with the aim of verifying whether or not CCSVI is linked to MS. The primary endpoint of the CoSMo study is to compare the prevalence of CCSVI in patients with MS versus patients affected by other neurodegenerative diseases (OND) and healthy volunteers. CoSMo is a multicenter, blinded, prevalence study recruiting 2,000 adult subjects, involving 43 MS centers across Italy. Assessment of the presence or absence of CCSVI is performed by color-coded duplex (CCD) sonography and two out of the five criteria according to Zamboni are necessary for the diagnosis of CCSVI. Local CCD examination carried out by a certified sonologist and the central image readings performed by experts in the field are blinded. An advanced protocol is also described in this paper. The application of a rigorous methodological design will definitively confirm whether an association exists between CCSVI and MS. Should an association be observed, this study also further examines the link between CCSVI and the severity of MS. The addition of subgroups without MS and OND also provides information on whether CCSVI is specific to MS only. Results from the CoSMo study will play a crucial role in the possible studies concerning the potential treatment of CCSVI in MS.

Cocaine dependence and stroke: pathogenesis and management.

Cocaine abuse remains a devastating medical problem for our society. Current concepts suggest that both hemorrhagic and ischemic stroke, particularly in young people, can result as a consequence of cocaine exposure. We provide an analysis of mechanisms of injury and a discussion of the pharmacological management of stroke following cocaine use. Preclinical research suggests that the cause of cocaine-mediated stroke is multifactorial and involves vasospasm, changes in cerebral vasculature, and platelet aggregation. We suggest that drugs able to induce vasospastic, thrombogenic, or neurotoxic effects of cocaine could be suitable as therapeutic agents. In contrast caution should be exerted when using anti-platelet and thrombolytic agents in cocaine users with stroke.

The National Institutes of Health Stroke Scale: Its Role in Patients with Posterior Circulation Stroke

ABSTRACT The National Institutes of Health Stroke Scale (NIHSS) is indispensable for both prognosis and treatment in patients with acute ischemic stroke. However, there is subtype of acute ischemic stroke (i.e., posterior circulation stroke) that is difficult to diagnose using the NIHSS. The authors report the limits of NIHSS in this stroke subtype, suggesting thereby the need to modify and render it more appropriate for the evaluation of the neurological signs occurring in posterior circulation stroke.