Rosella Ciurleo

Evaluation of olfactory dysfunction in neurodegenerative diseases

It is known that the olfactory dysfunction is involved in various neurological diseases, such as Parkinsons disease, Alzheimers disease, multiple sclerosis, Huntingtons disease and motor neuron disease. In particular, the ability to identify and discriminate the odors, as well as the odor threshold, can be altered in these disorders. These changes often occur as early manifestation of the pathology and they are not always diagnosed on time. The aim of this review is to summarize the major neurological diseases which are preceded or accompanied by olfactory dysfunction. In addition, new instrumental approaches, such as psychophysical testing, olfactory event-related potentials (OERPs) and functional magnetic resonance imaging (fMRI) measurements, supported by olfactometer for the stimuli delivery, and their combination in evaluation of olfactory function will be discussed. In particular, OERPs and fMRI might to be good candidates to become useful additional tools in clinical protocols for early diagnosis of neurological diseases.

1H-MR Spectroscopy in Traumatic Brain Injury

Traumatic brain injury (TBI) is a common cause of neurological damage and disability. Conventional imaging (CT scan or MRI) is highly sensitive in detecting lesions and provides important clinical information regarding the need for acute intervention. However, abnormalities detected by CT scan or conventional MRI have limited importance in the classification of the degree of clinical severity and in predicting patients’ outcome. This can be explained by the widespread microscopic tissue damage occurring after trauma, which is not observable with the conventional structural imaging methods. Advances in neuroimaging over the past two decades have greatly helped in the clinical care and management of patients with TBI. The advent of newer and more sensitive imaging techniques is now being used to better characterize the nature and evolution of injury and the underlying mechanisms that lead to progressive neurodegeneration, recovery or subsequent plasticity. This review will describe the role of proton magnetic resonance spectroscopic (MRS), an advanced MRI technique as related to its use in TBI. Proton MRS is a noninvasive approach that acquires metabolite information reflecting neuronal integrity and function from multiple brain regions and allows to assess clinical severity and to predict disease outcome.

Role of resveratrol and its analogues in the treatment of neurodegenerative diseases: focus on recent discoveries.

Neurodegenerative diseases are a group of chronic, progressive disorders characterized by the gradual loss of neurons in several areas of the central nervous system (CNS). Substantial evidence has documented a common inflammatory mechanism in neurodegeneration. It is known that classical anti-inflammatory agents, steroids and nonsteroidal anti-inflammatory drugs, have not played a major role in the management of CNS inflammatory conditions. This may be partly due to the natural compartmentation of the brain by the blood-brain barrier. Thus, there is much interest in developing novel anti-inflammatory drugs that may help to prevent or ameliorate CNS inflammation. Resveratrol (RSV) has received considerable attention over the last several decades. Experimental studies have revealed its benefits in several human disease models, including cardio- and neuro-protection, immune regulation and cancer chemoprevention. The broad action spectrum of RSV is explained by the involvement of numerous signaling networks and cellular effector mechanisms. Among them, apoptotic and antioxidant targets have been implicated. Recently, also anti-neuroinflammatory activity has been observed. A number of studies demonstrated that RSV mediates the downregulation of various inflammatory biomarkers such as tumor necrosis factor, cyclooxygenase 2, inducible nitric oxide synthase and interleukins. This activity seems to depend on some structural features of RSV such as the number and the position of hydroxyl groups. In this review, a comprehensive account of multiple intracellular RSV targets involved in neuroinflammation and its analogues design will be treated, pointing to structure/activity relationships.

Pharmacotherapy for Disorders of Consciousness: Are ‘Awakening’ Drugs Really a Possibility?

Disorders of consciousness, including the coma state, vegetative state and minimally conscious state, are among the least understood and least curable conditions in modern neurology. Structural or functional injuries may produce impairments in the neuronal circuits (the ascending reticular activating system and thalamocortical loops) responsible for maintaining the wakefulness state and awareness, associated with a change in neurotransmitter concentrations. Pharmacological agents that are able to restore the levels of neurotransmitters and, consequently, neural synaptic plasticity and functional connectivity of consciousness networks, may play an important role as drugs useful in improving the consciousness state. Currently, there is growing interest in the scientific community with regard to pharmacological agents that act on the gamma amino-butyric acid (GABA) system, such as zolpidem and baclofen, and monoamine systems, such as dopaminergic agents and some antidepressants. The purpose of this article is to provide a comprehensive overview of these potential ‘awakening’ drugs in patients with disorders of consciousness. The possible mechanisms by which these drugs may exert their effects in promoting recovery of consciousness are discussed, highlighting how many findings are often the result of sporadic events rather than prospective controlled trials or implementation of standard treatment guidelines.

Magnetic Resonance Spectroscopy: An In Vivo Molecular Imaging Biomarker for Parkinson's Disease?

Parkinsons disease (PD) is a neurodegenerative disorder caused by selective loss of dopaminergic neurons in the substantia nigra pars compacta which leads to dysfunction of cerebral pathways critical for the control of movements. The diagnosis of PD is based on motor symptoms, such as bradykinesia, akinesia, muscular rigidity, postural instability, and resting tremor, which are evident only after the degeneration of a significant number of dopaminergic neurons. Currently, a marker for early diagnosis of PD is still not available. Consequently, also the development of disease-modifying therapies is a challenge. Magnetic resonance spectroscopy is a quantitative imaging technique that allows in vivo measurement of certain neurometabolites and may produce biomarkers that reflect metabolic dysfunctions and irreversible neuronal damage. This review summarizes the abnormalities of cerebral metabolites found in MRS studies performed in patients with PD and other forms of parkinsonism. In addition, we discuss the potential role of MRS as in vivo molecular imaging biomarker for early diagnosis of PD and for monitoring the efficacy of therapeutic interventions.

Neurogenic Ejaculatory Disorders: Focus on Current and Future Treatments

Ejaculation is a complex and still poorly understood neurological mechanism, at both spinal and cerebral levels as it is closely associated with orgasm. Physiologically, ejaculation is defined as the expulsion of seminal fluid from the urethral meatus and consists of two phases, namely emission and expulsion. Ejaculation is mediated by a spinal control center, referred to as a spinal pattern generator that coordinates sympathetic, parasympathetic and motor (somatic) outflows, integrating the latter with the inputs from the supraspinal sites in brainstem, hypothalamus and preoptic area. Premature ejaculation (PE) is the most common sexual dysfunction among young men, and it has been considered mostly psychogenic in origin, although it can be associated to diverse urological and neurological diseases. On the contrary, retrograde ejaculation and anejaculation are predominantly related to organic causes, particularly to neurogenic ones. Since ejaculation is mostly a spinal reflex, it is comprehensible that ejaculatory disorders are more frequent in spinal cord injury than in other neurological disorders. Over the past decades, research has focused on PE, and evidence from clinical studies showed a beneficial effect of antidepressants for the treatment of men with PE. Other ejaculatory disorders, especially painful ejaculation, have been less investigated and the proper therapy is still controversial. Aim of this review is to provide a comprehensive description of both currently available treatments and most promising future therapies, including assigned patents, for the neurogenic ejaculatory disorders.

Persistent anosmia in a traumatic brain injury patient: Role of orbitofrontal cortex

Abstract Background: The olfactory loss due to traumatic brain injury is a common clinical condition. The understanding of the cortical areas involved in ability to detect, discriminate and identify the odours is still limited. However, it has been shown that the orbitofrontal cortex (OFC) is involved in the discrimination and recognition of odours and in particular the right OFC has a dominant role in the central processing of smell. Method: This study used the Sniffin’ Sticks Test to evaluate olfactory function of a 40-year-old female with persistent post-traumatic anosmia and to have a objective measure method for the follow-up. Results: A marked decrease in the ability to identify and discriminate odours was found. On the other hand the ability to perceive the odours was little compromised. A cerebral Magnetic Resonance Imaging, performed 10 months after the trauma, showed the presence of a post-traumatic scarring in the right frontal lobe involving the OFC. Conclusions: In this case of post-traumatic anosmia, the ability to perceive and recognize odours does not seem to be compromised in the same measure. It is postulated that the post-traumatic outcomes, involving areas of multisensory integration such as the OFC, have an important pathogenetic role in the loss of ability to recognize and discriminate odours.

Magnetic resonance imaging markers for early diagnosis of Parkinson's disease

Parkinsons disease (PD) is a neurodegenerative disorder characterized by selective and progressive degeneration, as well as loss of dopaminergic neurons in the substantia nigra. In PD, approximately 60-70% of nigrostriatal neurons are degenerated and 80% of content of the striatal dopamine is reduced before the diagnosis can be established according to widely accepted clinical diagnostic criteria. This condition describes a stage of disease called “prodromal”, where non-motor symptoms, such as olfactory dysfunction, constipation, rapid eye movement behaviour disorder, depression, precede motor sign of PD. Detection of prodromal phase of PD is becoming an important goal for determining the prognosis and choosing a suitable treatment strategy. In this review, we present some non-invasive instrumental approaches that could be useful to identify patients in the prodromal phase of PD or in an early clinical phase, when the first motor symptoms begin to be apparent. Conventional magnetic resonance imaging (MRI) and advanced MRI techniques, such as magnetic resonance spectroscopy imaging, diffusion-weighted and diffusion tensor imaging and functional MRI, are useful to differentiate early PD with initial motor symptoms from atypical parkinsonian disorders, thus, making easier early diagnosis. Functional MRI and diffusion tensor imaging techniques can show abnormalities in the olfactory system in prodromal PD.

Metabolic changes in de novo Parkinson's disease after dopaminergic therapy: A proton magnetic resonance spectroscopy study.

The aim of this study was to assess metabolic changes in the motor cortex in de novo Parkinsons disease (PD) patients before and after therapy with ropinirole. Twenty de novo drug-naïve PD patients and 15 healthy controls underwent conventional magnetic resonance imaging and proton magnetic resonance spectroscopy imaging ((1)H-MRSI). The resonance intensities of N-acetylaspartate (NAA) and choline (Cho) were normalized for the resonance intensities of creatine (Cr). At baseline, lower NAA/Cr and NAA/Cho ratios and higher Cho/Cr ratios were found in the motor cortex of PD patients compared with controls (p<0.001). Ten months after ropinirole treatment, PD patients showed a significant clinical improvement in the UPDRS motor sub-scores (p<0.001) and an increase of NAA/Cr and NAA/Cho ratios (p<0.006 and p=0.01, respectively). A highly significant correlation between NAA/Cr and NAA/Cho ratios and UPDRS motor sub-scores was observed (r=-0.981 and r=-0.983, respectively). We could argue that the ropinirole efficacy to improve the motor performances is the result of partial restoration of neuronal functions, due to the increase of NAA in motor cortex.

The role of Sativex in robotic rehabilitation in individuals with multiple sclerosis: Rationale, study design, and methodology

Introduction: Currently, none of the available multiple sclerosis (MS) disease-modifying medications has been shown to stop or reverse gait disability. Recently, the nabiximols has been tested for the treatment of spasticity and walking impairment in MS. Nabiximols (trade name Sativex) is an oromucosal spray formulation containing 1:1 fixed ratio of delta-9-tetrahydrocannabinol and cannabidiol derived from cloned Cannabis sativa L. plant. Method and analysis: A single-center, prospective, parallel design, single-blind trial will be conducted at the IRCCS Neurolesi “Bonino-Pulejo” (Italy) involving MS patients affected by spasticity and undergoing a Robotic Rehabilitation training. The aim of the study is to clarify the role of Sativex coupled to a robotic neurehabilitation training in MS patients in improving motor outcomes, by means of clinical, kinematic, and neurophysiological measures. Patients will be randomly divided in 2 groups: one taking only an oral antispastic drug and the other with Sativex in add-on. After 1 month, we will evaluate the response to Sativex (responder patients’ amelioration >20% at MRS score) enrolling into the study the first 20 patients with a good response to Sativex, whereas other 20 no-responder individuals will continue their antispastic drug. All the 40 subjects, were divided into 2 groups (A: Sativex + Lokomat Training, and B: other antispastic+Lokomat Training), will perform a neurorobotic-assisted gait training (each session will last at least 45 minutes, 3 times per week, for a total of 20 sessions). All the patients will undergo a complete physical and neurological examination at baseline, at the end of the robotic training (T1), and 30 days after the end of the neurorehabilitation training (T2).