Parkinson's disease is the second most common neurodegenerative disease worldwide. There is widespread consensus that Parkinson patients, their carers, and clinicians involved in their care would benefit from a fully integrated, need-based provision of palliative care. However, the concept of palliative care in Parkinson's disease is still poorly defined and, consequently, poorly implemented into daily clinical practice. A particular challenge is the gradually progressive nature of Parkinson's disease—with insidiously increasing disability—making it challenging to clearly define the onset of palliative care needs for Parkinson patients. As people with Parkinson's disease are now living longer than in the past, future research needs to develop a more robust evidence-based approach to clarify the disease events associated with increased palliative care needs, and to examine these, prospectively, in an integrated palliative care service. The modern palliative care outlook, termed "simultaneous care,",is no longer restricted to the final stage of disease. It involves incorporating a continuity of care, effective management of the chronic-palliative interface, and a multidisciplinary network of professionals working both in the community and in specialized clinics, with active involvement of caregivers. Although promising, there is still a need to demonstrate the effectiveness of palliative care for patients with Parkinson's disease.
The development of biomarkers is of great importance in Parkinson's disease (PD) as it may contribute to confirmation and support of the diagnosis, tracking of progression, and prediction of the natural history of PD. Biomarkers also help in the identification of targets for treatment and measuring the efficacy of interventions. Biomarkers are, therefore, crucial to understanding the pathophysiology of PD, the second commonest neurodegenerative disorder in the world. Modern understanding of PD suggests that it is a multipeptide, multiorgan disorder presenting with a heterogeneous clinical condition, both motor and nonmotor. Biomarkers need to reflect this neuropathological and clinical heterogeneity of PD. In this review, we outline some key advances in the field of clinical, genetic, neuroimaging, and tissue-based biomarkers proposed or used for PD. The individual sections will be covered in relevant chapters and our review is largely a primer aimed to alert readers to the current state of the various biomarkers proposed for PD. In doing so, we have also underlined the important role multimodal rather than single biomarkers could play in our future understanding of PD.
Parkinson's disease (PD) is now known to be a multisystemic and multipeptide neurodegenerative disorder, whereby patients have an array of symptoms both motor and nonmotor. Nonmotor features of PD have been shown to arise almost 15-20 years prior to motor symptoms and, as such, are also a key determinant to the quality of life of a patient. Therefore, there is increasing evidence that a PD patient's management must encompass a multidisciplinary approach to effectively manage and treat the patient's PD and also their individual symptoms. Therefore, the notion that a PD nurse specialist and a neurologist are the only key players, is no longer the case. Rather, the involvement of speech and language therapist, physiotherapists, palliative care, and others is vital for a patient's recovery and their effective management. Here we discuss a few professions who should ideally be present for each PD patient.
INTRODUCTION Multiple sclerosis is one of the commonest idiopathic inflammatory diseases of the central nervous system in young adults. The study of the natural history of multiple sclerosis implies in the first place, establishing precise limits for the diagnosis of the disease, which is still of unknown origin. It is also necessary to analyze the wide range of varieties, which as different categories or subgroups and with different degrees of severity, make up the clinical spectrum of this entity. DEVELOPMENT AND CONCLUSIONS Throughout this review benign and malignant multiple sclerosis, remitting and progressive forms, are studied from epidemiological and clinical points of view in the context of large populations of patients with multiple sclerosis on long-term follow up at a specialized centre, with the objective of finding, if possible, the patterns of the natural history of the disease.
SE in the pediatric age group presents challenges in diagnosis and management. There is need for renewed consensus on the temporal definition of SE, both clinical and electrographic. SE in children exhibits an age-dependent vulnerability, with genetic predisposition and etiology as determinants of susceptibility. Nonepileptic phenomena may mimic SE. Clinical and electrographic SE in neonates are relatively rare, while serial (clinical and electrographic) and repetitive seizures are more common. Neurometabolic disease, chromosomal disorders, and abnormalities of cortical development are important etiological considerations. Abrupt discontinuation of or an aberrant response to AEDs can also precipitate SE. Metabolic perturbations and toxins can further aggravate the situation. Clinical and experimental data suggest that the longer a seizure lasts, the more difficult it becomes to control, and that seizures can have immediate and long-term adverse consequences on the immature and developing brain. Hence, treatment (usually with a benzodiazepine) should be started early in the clinical course. A trial of pyridoxine, biotin, or folinic acid should be considered in the appropriate clinical setting (e.g., neonates or young infants, in particular). Phenytoin/fosphenytoin and phenobarbital remain important treatment options. Pentobarbital and midazolam are preferred choices in the management of RSE. Once metabolic causes are excluded, children with RSE should be evaluated for surgical treatment early in the clinical course. Clinical guidelines based on best available evidence have to be periodically reviewed. The clinical consequences and management of electrographic SE, especially in the neonate, have to be addressed. Guidelines for continuous (video) EEG monitoring are needed to facilitate this task. AEDs that do not have an adverse effect on the developing brain have to be developed. Our review suggests a continuing need for prospective studies into all aspects of SE in the pediatric age group.
Both women and men with epilepsy run significant risks of reproductive dysfunction. These problems are seldom addressed, however, either by the medical profession or by lay organizations. Many physicians are not even aware of these health risks. Increased awareness of--and treatment of--these problems are important goals for the future.
Drug resistance is a feature of different forms of epilepsy or epileptic syndromes. It is defined as the persistence of unacceptable seizures despite reasonable pharmacotherapy and drug use to the highest tolerable dosage. It affects between 20% and 30% of patients with epilepsy overall (1). In subgroups of epilepsy patients, a particularly high incidence of drug resistance is encountered (e.g., in patients with focal or partial epilepsies). Clinical predictive factors for later pharmacoresistance are febrile seizures lasting longer than 30 min and displaying focal signs, certain forms of status epilepticus, and developmental alterations such as microcephaly. Apart from infantile spasms and neonatal seizures, atonic seizures are frequently pharmacoresistant (2). Kanazawa (3) pointed out that certain seizure syndromes are frequently associated with pharmacoresistance. These include the Ohtahara syndrome, Dravets syndrome, West syndrome, Rasmussen encephalitis, Lennox Gastaut syndrome, and the migrating focal seizures during infancy. Hence, drug resistance may be already present when first treatment is initiated, or it may arise during the course of chronic epilepsy following an initially positive response. In
Preclinical models, if used appropriately, can greatly accelerate the understanding of neuropsychiatric disorders. A number of animal models have predictive validity for antidopaminergic compounds that have traditionally been used to suppress motor and vocal tics in TS. Other models have been proposed that may have construct validity for specific hypotheses of infectious/immune and neural circuit etiologies of TS. A more comprehensive set of models is described, based on the hypothesis that primary symptoms of TS, including sensory tics and premonitory urges, result from dysfunction in brain mechanisms that regulate sensorimotor gating. These models utilize operational measures of central gating mechanisms, including PPI of the startle reflex, to achieve predictive validity across a number of different chemical classes of drugs, and to achieve construct validity across broad domains of neurodevelopmental, immune and genetic etiologies of TS. PPI-based animal models offer a number of strong advantages for predictive and mechanistic studies of TS. Ultimately, the utility of these "deficient gating" models will be judged by their ability to bring us closer to identifying the causes and effective treatments of this disorder.
Tic symptoms, the hallmark of Tourette's syndrome (TS), may simply be fragments of innate behavior. As such, the sensory urges that precede tics may illuminate some of the normal internal cues that are intimately involved in the assembly of behavioral sequences. The occurrence of tics in time appears to have fractal characteristics that may help to explain the waxing and waning course of tic disorders. Longitudinal studies are currently underway that should permit a close examination of the natural fluctuations in tic severity using valid and reliable clinician-rated scales of tic severity. The natural history of tics typically shows a marked decline during the course of adolescence. However, TS can also be associated with social, emotional, and academic difficulties in early adulthood. Comorbid attention deficit/hyperactivity disorder and obsessive-compulsive disorder are likely to influence the long-term adaptive outcomes of individuals with TS. Future progress may also be expected as endophenotypes, and possibly genetic markers, are identified that are associated with specific comorbid conditions and etiologically distinct forms of TS.
