Front Microbiol 2017 20;8:1363. Epub 2017 Jul 20.

Unité de Recherche en Maladies Infectieuses et Tropicales Emergentes, UM63, Centre National De La Recherche Scientifique 7278, IRD 198, Institut National De La Santé Et De La Recherche Médicale U1095, Institut Hospitalo-Universitaire Méditerranée-Infection, Aix-Marseille UniversitéMarseille, France.

Arthropod-borne Rickettsia species are obligate intracellular bacteria which are pathogenic for humans. Within this genus, Rickettsia slovaca and Rickettsia conorii cause frequent and potentially severe infections, whereas Rickettsia raoultii and Rickettsia massiliae cause rare and milder infections. All four species belong to spotted fever group (SFG) rickettsiae. Read More

Pan Afr Med J 2017 20;26:80. Epub 2017 Feb 20.

Service de Neurlogie, Hopital Militaire Moulay Ismail, Meknès, Maroc.

Mediterranean spotted fever (MSF) is a rickettsiosis of the spotted fever group caused by rickettsia conorii. This zoonosis is benign but it can be complicated by severe neurological impairment (hence its severity). We report the case of a 49-year old patient hospitalized in the Department of Dermatology for rickettsiosis, who suffered from right massive hemiplegia of brutal onset. Read More

Ticks Tick Borne Dis 2017 Jun 12;8(4):610-614. Epub 2017 Apr 12.

SaBio. Instituto de Investigación en Recursos Cinegéticos, IREC (CSIC, UCLM, JCCM), Ronda de Toledo s/n, 13005 Ciudad Real, Spain; Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK 74078, USA. Electronic address:

Rickettsiae (family Rickettsiaceae, order Rickettsiales) are obligate intracellular bacteria transmitted by arthropod vectors. Several Rickettsia species causing vector-borne rickettsioses belong to the spotted fever group (SFG). Traditionally, Rickettsia conorii has been considered as the main etiologic agent of Mediterranean spotted fever. Read More

Int J Infect Dis 2017 Aug 10;61:7-12. Epub 2017 Apr 10.

Dipartimento di Scienze per la Promozione Della Salute e Materno-Infantile, Università di Palermo, Italy. Electronic address:

Mediterranean spotted fever (MSF) is endemic in Italy, where Rickettsia conorii subsp. conorii was thought to be the only pathogenic rickettsia and Rhipicephalus sanguineus the vector and main reservoir. R. Read More

J Infect Dev Ctries 2017 Mar 31;11(3):242-246. Epub 2017 Mar 31.

Faculty of Medicine, Mutah University, Karak, Jordan.

Introduction: The aim of this study was to describe the epidemiological patterns of Mediterranean spotted fever (MSF) as well as its treatment and outcomes in children in south Jordan.

Methodology: A retrospective observational study was conducted from June 2013 to December 2015. Data regarding demographics, clinical presentation, laboratory findings, treatment, and outcomes were collected. Read More

PLoS One 2017 29;12(3):e0174745. Epub 2017 Mar 29.

National Centre for Tropical Medicine, Health Institute Carlos III (ISCIII in Spanish), Madrid, Spain.

Introduction: Mediterranean spotted fever (MSF) is a zoonotic disease caused by Rickettsia conorii. In Spain, deficiencies in the official reporting result in misreporting of this disease. This study aims to describe the clinical and temporal-spatial characteristics of MSF hospitalizations between 1997 and 2014. Read More

JMM Case Rep 2016 Aug 30;3(4):e005039. Epub 2016 Aug 30.

Dipartimento di Scienze per la promozione della salute e materno-infantile, Università di Palermo , Italy.

Introduction: Mediterranean spotted fever (MSF) is a tick-borne acute febrile disease caused by Rickettsia conorii. Most cases follow a benign course, with a case fatality rate of 3-7 % among hospitalized patients. Complications are described mainly in adult patients and include hepatic, renal, neurological and cardiac impairment. Read More

Pan Afr Med J 2016 6;25:211. Epub 2016 Dec 6.

Chirurgie Générale à la Faculté de Médecine de Tunis, Hôpital de Zaghouan, Avenue de l'Environnement, 1100 Zaghouan, Tunisie.

Mediterranean spotted fever is an infectious disease belonging to the rickettsial group due to an intracellular bacterium: Rickettsia Conorii. Pauci-symptomatic and benign forms are predominant. Severe forms are rare and increasingly reported in the recent literature with potentially life-threatening severe multi-systemic involvement. Read More

Cureus 2017 Jan 12;9(1):e974. Epub 2017 Jan 12.

Department of Medicine, Overlook Medical Center.

We report a case of a 43-year-old Israeli male who presented with an intermittent fever associated with a gradual appearance of diffusely scattered erythematous non-pruritic maculopapular lesions, generalized body malaise, muscle aches, and distal extremity weakness. He works in the Israeli military and has been exposed to dogs that are used to search for people in tunnels and claimed that he had removed ticks from the dogs. In the hospital, he presented with fever, a diffuse maculopapular rash, and an isolated round black eschar. Read More

Case Rep Infect Dis 2016 7;2016:2421540. Epub 2016 Dec 7.

3rd Department of Internal Medicine, Hospital Distrital de Santarém, Santarém, Portugal.

Mediterranean spotted fever is a tick-borne zoonotic disease caused by Rickettsia conorii. It is transmitted by the dog tick Rhipicephalus sanguineus. It usually presents as a benign self-limited disease characterized by a skin rash, high fever, and, sometimes, a characteristic ulcer at the tick bite site called tache noir. Read More

J Neurol Sci 2016 Dec 14;371:60-61. Epub 2016 Oct 14.

Department of Neurology, "IASO General" Hospital, Athens, Greece; 251 Hellenic Airforce Hospital, Athens, Greece.

Sci Rep 2016 Nov 11;6:36728. Epub 2016 Nov 11.

Department of Pathology, The University of Texas Medical Branch, Galveston, TX, 77555, USA.

Small regulatory RNAs comprise critically important modulators of gene expression in bacteria, yet very little is known about their prevalence and functions in Rickettsia species. R. conorii, the causative agent of Mediterranean spotted fever, is a tick-borne pathogen that primarily infects microvascular endothelium in humans. Read More

Travel Med Infect Dis 2016 Sep - Oct;14(5):436-443. Epub 2016 Jul 9.

Medica, Medizinische Laboratorien Dr. F. Kaeppeli, Wolfbachstrasse 17, CH-8024 Zurich, Switzerland. Electronic address:

Aim: To review the current state of knowledge concerning rickettsiae and rickettsioses in Croatia and to discuss their implications for travellers.

Methods: The PubMed database was searched from 1991 to 2015 by combining the words "rickettsia," "rickettsiosis", "travellers" and "Croatia".

Results: Since 1969, Croatia appears to be free of epidemic typhus (ET) caused by Rickettsia prowazekii and the last case of Brill-Zinsser disease was recorded in 2008. Read More

Int J Dermatol 2017 Mar 1;56(3):252-259. Epub 2016 Oct 1.

Division of Clinical Dermatology, Mayo Clinic, Rochester, MN, USA.

Climate change refers to variation in the climate of a specific region or globally over time. A change has been reported in the epidemiology of tick- and mosquito-borne diseases in recent decades. Investigators have postulated that this effect may be associated with climate change. Read More

Arch Pediatr 2016 Oct 15;23(10):1076-1079. Epub 2016 Sep 15.

Hedi Chaker hospital, pediatric department, Sfax, Tunisia; Faculty of medicine, Sfax, Tunisia.

Since the Arab Spring, a resurgence of zoonotic diseases such as rickettsiosis, endemic in the Mediterranean basin, has been observed. It preferentially infects microvascular endothelial cells of mammalian hosts inducing vasculitis with endothelial injury. Rickettsioses are considered benign infectious diseases. Read More

Jpn J Infect Dis 2016 ;69(4):352

Animal Health Department, University of Extremadura.

Jpn J Infect Dis 2016 ;69(4):352-4

Department of Microbiology, Hospital General La Mancha Centro.

Front Cell Infect Microbiol 2016 29;6:80. Epub 2016 Jul 29.

Vector Borne Disease Laboratories, Department of Pathobiological Sciences, LSU School of Veterinary Medicine Baton Rouge, LA, USA.

Spotted fever group (SFG) rickettsiae are recognized as important agents of human tick-borne diseases worldwide, such as Mediterranean spotted fever (Rickettsia conorii) and Rocky Mountain spotted fever (Rickettsia rickettsii). Recent studies in several animal models have provided evidence of non-endothelial parasitism by pathogenic SFG Rickettsia species, suggesting that the interaction of rickettsiae with cells other than the endothelium may play an important role in pathogenesis of rickettsial diseases. These studies raise the hypothesis that the role of macrophages in rickettsial pathogenesis may have been underappreciated. Read More

Indian J Med Microbiol 2016 Jul-Sep;34(3):293-8

Department of Pediatrics, St. John's Medical College Hospital, Bengaluru, Karnataka, India.

Background: Rickettsial infections are re-emerging. In India, they are now being reported from several areas where they were previously unknown.

Objectives: The objective of this study was to describe the epidemiology, clinical profile and outcome of serologically-confirmed scrub typhus and spotted fever among children in a tertiary care hospital in Bengaluru. Read More

Braz J Infect Dis 2016 Sep-Oct;20(5):511-2. Epub 2016 Jul 21.

Medical University, Faculty of Medicine, Department of Clinical Pathology, Plovdiv, Bulgaria.

Eur Rev Med Pharmacol Sci 2016 Jun;20(12):2630-3

Department of Medical Sciences, Internal Medicine and Gastroenterology Unit, Catholic University of the Sacred Heart, Gemelli Hospital, School of Medicine, Rome, Italy.

Objective: Rickettsia conorii is responsible for the Mediterranean Spotted Fever. Recently, new rickettsial species have been recognized in Europe and implicated in human diseases. Clinical features often differ greatly from each other, but non-severe liver involvement is frequently observed during any rickettsial infection. Read More

Infection 2016 Dec 5;44(6):733-738. Epub 2016 Jul 5.

Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 8, 07100, Sassari, Italy.

Introduction: Rickettsioses represent a group of emerging infectious diseases in Europe. Climate changes and the anthropization of rural environment have favored vectors' biological cycle and geographic spread. In Sardinia, Mediterranean spotted fever (MSF) is endemic and represents an important public health problem. Read More

Clin Microbiol Infect 2016 Aug 20;22(8):734.e1-6. Epub 2016 May 20.

Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway. Electronic address:

Mediterranean spotted fever caused by Rickettsia conorii is a potentially lethal disease characterized by vascular inflammation affecting multiple organs. Studies of R. conorii so far have focused on activation of inflammatory cells and their release of inflammatory cytokines, but complement activation has not been investigated in R. Read More

Parasit Vectors 2016 05 20;9(1):294. Epub 2016 May 20.

Department of Parasitology and Parasitic Diseases, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, Calea Mănăştur 3-5, Cluj Napoca, Romania.

Background: Birds are important hosts and dispersers of parasitic arthropods and vector-borne zoonotic pathogens. Particularly migratory species may carry these parasites over long distances in short time periods. Migratory hotspots present ideal conditions to get a snapshot of parasite and pathogen diversity of birds migrating between continents. Read More

Parasit Vectors 2016 05 20;9(1):291. Epub 2016 May 20.

Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, MS, 39406, USA.

Background: The Gulf Coast tick (Amblyomma maculatum) is an arthropod vector of Rickettsia parkeri, the causative agent of American boutonneuse fever and an infectious agent of public health significance. In this study, we evaluated the biological significance of the superoxide dismutases (SODs) of A. maculatum in hematophagy and R. Read More

Cytokine 2016 Jul 12;83:269-274. Epub 2016 May 12.

Department of Immunology, Oslo University Hospital Rikshospitalet, P.B. 4950 Nydalen, 0424 Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, P.B. 4950 Nydalen, 0424 Oslo, Norway.

Background: The pathophysiological hallmark of Rickettsia conorii (R. conorii) infection comprises infection of endothelial cells with perivascular infiltration of T-cells and macrophages. Although interferon (IFN)-γ-induced protein 10 (IP-10)/CXCL10 is induced during vascular inflammation, data on CXCL10 in R. Read More

Parasitol Res 2016 Sep 30;115(9):3323-8. Epub 2016 Apr 30.

Dipartimento di Medicina Veterinaria, Università degli studi di Sassari, Sassari, Italy.

Rickettsia aeschlimannii is an emerging tick-borne pathogen of the spotted fever group Rickettsiae with considerable impact on both human and animal health. This study reports the molecular detection and groEL characterization of R. aeschlimannii in ticks collected from birds and ruminants in a typical Mediterranean environment. Read More

Lab Chip 2016 Apr;16(9):1625-35

Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas, USA. and Centro de Biotecnología FEMSA, Tecnológico de Monterrey, Campus Monterrey, Monterrey, Nuevo León, Mexico.

We present a microfluidic immunoassay platform based on the use of linear microretroreflectors embedded in a transparent polymer layer as an optical sensing surface, and micron-sized magnetic particles as light-blocking labels. Retroreflectors return light directly to its source and are highly detectable using inexpensive optics. The analyte is immuno-magnetically pre-concentrated from a sample and then captured on an antibody-modified microfluidic substrate comprised of embedded microretroreflectors, thereby blocking reflected light. Read More

Enferm Infecc Microbiol Clin 2017 Feb 11;35(2):100-103. Epub 2016 Mar 11.

Servicio de Pediatría, Hospital Universitari Sant Joan de Reus, Reus, Tarragona, España.

Rickettsia diseases are a group of tick-borne transmitted diseases, classified into 2 large groups: spotted fevers and typhus fevers. In addition, a new condition has been described recently, known as tick-borne lymphadenopathy. A retrospective series is presented of paediatric cases of rickettsia diseases diagnosed in 2013 and 2014. Read More

Folia Med (Plovdiv) 2015 Apr-Jun;57(2):93-103

Introduction: Mediterranean spotted fever (MSF) in Bulgaria is caused by Rickettsia conorii conorii.

Aim: This study aims at investigating the absolute counts of T-lymphocyte subsets in the peripheral blood of patients with MSF in order to establish relationships with disease severity.

Materials And Methods: The absolute counts of T-lymphocyte subsets were tested in the blood of 62 patients in the acute stage of MSF. Read More

Indian Dermatol Online J 2015 Dec;6(Suppl 1):S1-4

Department of Dermatology, Jawaharlal Nehru Medical College, Belgaum, Karnataka, India.

Fever with rash is one of the most common causes of referral to a dermatologist. A plethora of conditions need to be considered in the differential diagnosis. They may be broadly classified into infectious causes, drug reactions, and autoimmune disorders. Read More

Epidemiol Infect 2016 Jul 22;144(9):1889-94. Epub 2016 Feb 22.

Infectious Diseases Unit,Internal Medicine Service,Hospital de Terrassa,Terrassa,Spain.

The incidence of Mediterranean spotted fever (MSF) in Catalonia (Spain) has decreased in the last two decades. The prevalence of antibodies to Rickettsia conorii in human beings and dogs in the region of Vallès Occidental (Catalonia) was assessed by indirect immunofluorescence, and the results compared with those obtained in a similar study from 1987. Nineteen (5·0%) out of 383 human serum samples had antibodies to R. Read More

Ticks Tick Borne Dis 2016 Jul 8;7(5):653-656. Epub 2016 Feb 8.

Laboratory of Microbiology, Research Laboratory "MPH", Habib Bourguiba University Hospital of Sfax, Sfax University, Sfax, Tunisia.

Diagnosis of rickettsioses had largely benefited from the development of molecular techniques. Unfortunately, in Tunisia, despite the large number of rickettsial cases registered every year, the Rickettsia species remain unidentified. In this study, we aimed to detect the Rickettsia species in clinical samples using molecular tests. Read More

Ticks Tick Borne Dis 2016 Apr 19;7(3):457-61. Epub 2016 Jan 19.

Corporació Sanitària Parc Taulí - Institut Universitari Parc Taulí - Universitat Autonoma de Barcelona, Parc Taulí 1, Sabadell, Barcelona, 08208, Spain. Electronic address:

Rickettsia conorii and Rickettsia massiliae-Bar29 are related to Mediterranean spotted fever (MSF). They are intracellular microorganisms. The Shell-vial culture assay (SV) improved Rickettsia culture but it still has some limitations: blood usually contains low amount of microorganisms and the samples that contain the highest amount of them are non-sterile. Read More

Ann Ist Super Sanita 2015 ;51(4):284-90

Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy.

Background: Ticks are vectors and important reservoirs for microbial agents that cause disease in humans and animals. Among these pathogens, the members of Rickettsia species play an important role in public health.

Aim And Methods: One hundred twenty-nine ticks belonging to four tick species (Ixodes ricinus, Rhipicephalus turanicus, Dermacentor marginatus, and Haemaphysalis punctata) were collected at different sites of the Insugherata Natural Reserve, localized in the urban area of Rome, Italy. Read More

Infect Immun 2016 Jan 11;84(3):790-7. Epub 2016 Jan 11.

Vector Borne Disease Laboratories, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA

Scientific analysis of the genus Rickettsia is undergoing a rapid period of change with the emergence of viable genetic tools. The development of these tools for the mutagenesis of pathogenic bacteria will permit forward genetic analysis of Rickettsia pathogenesis. Despite these advances, uncertainty still remains regarding the use of plasmids to study these bacteria in in vivo mammalian models of infection, namely, the potential for virulence changes associated with the presence of extrachromosomal DNA and nonselective persistence of plasmids in mammalian models of infection. Read More

Med Parazitol (Mosk) 2015 Jul-Sep(3):17-21

The paper analyzes data on the prevalence and possible epidemiological importance of Rickettsia raoultii. The possible risk of infection in the population was assessed from the results of a serological study of patients after tick suction and from those of molecular biological determination of contamination of removed carriers. The place of Rickettsia raoultii among other rickettsia causing rickettsioses of a tick-borne spotted fever group is assessed in Russia. Read More

Antimicrob Agents Chemother 2015 Dec 28;60(3):1642-5. Epub 2015 Dec 28.

Department of Infectious Diseases, Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain.

The classic antibiotic treatment for Mediterranean spotted fever (MSF) is based on tetracyclines or chloramphenicol, but chloramphenicol's bone marrow toxicity makes tetracyclines the treatment of choice. However, it is convenient to have alternatives available for patients who are allergic to tetracyclines, pregnant women, and children <8 years old. We conducted a randomized clinical trial to compare clarithromycin with doxycycline or josamycin in the treatment of MSF. Read More

BMC Genomics 2015 Dec 18;16:1075. Epub 2015 Dec 18.

Department of Pathology, the University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA.

Background: Rickettsia species are obligate intracellular Gram-negative pathogenic bacteria and the etiologic agents of diseases such as Rocky Mountain spotted fever (RMSF), Mediterranean spotted fever, epidemic typhus, and murine typhus. Genome sequencing revealed that R. prowazekii has ~25 % non-coding DNA, the majority of which is thought to be either "junk DNA" or pseudogenes resulting from genomic reduction. Read More

Acta Med Port 2015 Sep-Oct;28(5):624-31. Epub 2015 Oct 30.

Unidade de Cuidados Intermédios Médico-Cirúrgicos. Centro Hospitalar do Porto. Porto. Portugal.

Introduction: Mediterranean spotted fever, an ancient zoonotic disease raising current issues. This study aims to reevaluate the disease clinical picture and to identify prognostic factors related to severe disease.

Material And Methods: We evaluate cases admitted to a central hospital during 12-year period. Read More

Mol Cell Proteomics 2016 Jan 11;15(1):289-304. Epub 2015 Nov 11.

From the Departments of ‡Internal Medicine and §Institute for Translational Sciences, and ¶Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, Texas 77555-1060,

Rickettsia conorii is the etiologic agent of Mediterranean spotted fever, a re-emerging infectious disease with significant mortality. This Gram-negative, obligately intracellular pathogen is transmitted via tick bites, resulting in disseminated vascular endothelial cell infection with vascular leakage. In the infected human, Rickettsia conorii infects endothelial cells, stimulating expression of cytokines and pro-coagulant factors. Read More

Rev Neurol 2015 Nov;61(10):471

Complejo Hospitalario Universitario de Albacete, Albacete, Espana.

Pathog Dis 2015 Dec 29;73(9):ftv101. Epub 2015 Oct 29.

University of Chicago, Department of Microbiology, Chicago, IL 60637, USA Howard T. Ricketts Laboratory, Argonne, IL 60439, USA Vector-Borne Disease Laboratories, Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USA

Spotted fever group (SFG) rickettsial species are obligate intracellular tick-borne pathogens that are responsible for important human diseases. Previous reports have demonstrated the feasibility of using recombinant surface cell antigen Sca5/OmpB to elicit protective immunity against homologous challenges using murine models of Mediterranean spotted fever and Rocky Mountain spotted fever. In addition, the feasibility of generating cross-protective immunity against related rickettsial species has also been established, but the molecular basis for these phenomena was not explored. Read More

Microbes Infect 2015 Nov-Dec;17(11-12):811-6. Epub 2015 Sep 30.

Institute of Microbiology, University of Lausanne, University Hospital Center, Lausanne, Switzerland. Electronic address:

Coxiella burnetii and members of the genus Rickettsia are obligate intracellular bacteria. Since cultivation of these organisms requires dedicated techniques, their diagnosis usually relies on serological or molecular biology methods. Immunofluorescence is considered the gold standard to detect antibody-reactivity towards these organisms. Read More

PLoS One 2015 22;10(9):e0138830. Epub 2015 Sep 22.

Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.

Rickettsiae primarily target microvascular endothelial cells. However, it remains elusive how endothelial cell responses to rickettsiae play a role in the pathogenesis of rickettsial diseases. In the present study, we employed two rickettsial species with high sequence homology but differing virulence to investigate the pathological endothelial cell responses. Read More

Rev Esp Salud Publica 2015 May-Jun;89(3):321-8

Background: The Mediterranean Spotted Fever (MSF) is a zoonosis, produced by Rickettsia conorii whose vector is Rhipicephallus sanguineus. The aim of this study was to describe the epidemiology in Spain and its Autonomous Communities (AA.CC) and the average cost during the period 2009-2012. Read More

Microbes Infect 2015 Nov-Dec;17(11-12):834-8. Epub 2015 Sep 16.

Infectious Diseases Department, Hospital San Pedro-CIBIR, Logroño, Spain. Electronic address:

Bacteria of the genera Rickettsia and Orientia (family rickettsiaceae, order rickettsiales) cause rickettsioses worldwide, and are transmitted by lice, fleas, ticks and mites. In Europe, only Rickettsia spp. cause rickettsioses. Read More

Microbes Infect 2015 Nov-Dec;17(11-12):870-3. Epub 2015 Sep 3.

Intensive Care Unit, Zadar General Hospital, Zadar, Croatia; Faculty of Medicine, University of Osijek, Osijek, Croatia.

Mediterranean spotted fever (MSF) is usually a mild endemic rickettsial disease occurring in southern Croatia. We have reported the clinical and epidemiological characteristics of an acute MSF case associated with severe respiratory distress syndrome and hemodynamical instability. The patient recovered completely after antimicrobial treatment. Read More

Int J Dermatol 2015 Oct 14;54(10):e430-1. Epub 2015 Jul 14.

Department of Dermatology, Hospital El Bierzo, Ponferrada, Spain.

Neurol Sci 2015 Nov 8;36(11):2141-3. Epub 2015 Jul 8.

Department of Clinical and Experimental Medicine, Neurology Unit, University of Pisa, Via Roma 67, 56126, Pisa, Italy.