Autosomal dominant dystonia-plus with cerebral calcifications.

OBJECTIVE: To report genealogic, clinical, imaging, neuropathologic, and genetic data from a Canadian kindred with dystonia and brain calcinosis originally described in 1985. METHODS: The authors performed clinical examinations and CT and PET studies of the head and analyzed blood samples. One autopsy was performed. RESULTS: The family tree was expanded to 166 individuals. No individuals were newly affected with dystonia, but postural tremor developed in two. The mean age at symptom onset was 19 years. Eight individuals had dystonia: three focal, one segmental, one multifocal, and three generalized. Seven displayed additional signs: chorea, intellectual decline, postural tremor, and dysarthria. CT studies were performed on five affected and 10 at-risk family members. All affected individuals and eight at-risk individuals had brain calcinosis. PET scans in two individuals showed reduced D(1)- and D(2)-receptor binding and reduced uptake of 6-[(18)F]fluoro-l-dopa. Autopsy of one affected individual showed extensive depositions of calcium in the basal ganglia, thalamus, cerebral white matter, and cerebellum. No specific immunohistochemistry abnormalities were seen. Genome search data showed no evidence of linkage to the previously described loci IBGC1, DYT1, and DYT12. CONCLUSIONS: The phenotype of this family consists of dystonia-plus syndrome. Brain calcium deposits vary in severity and distribution, suggesting that calcifications alone are not entirely responsible for the observed clinical signs. Further studies are needed to elucidate the etiology of this heterogeneous group of disorders.

Nocturnal sleep disturbances and daytime dysfunction in patients with Parkinson's disease and in their caregivers.

BACKGROUND: The role of aging, disease, medications, and mood disturbances in sleep disturbances (SD) in patients with Parkinson's disease (PD) is poorly understood, and the impact of SD on the quality of life of their caregivers (CG) largely undocumented. OBJECTIVES: To evaluate the pattern and determinants of disturbed sleep in PD patients complaining of SD, and in their primary CG. METHODS: A prospective evaluation of 40 non-demented patients with PD complaining of SD and 23 of their primary CG (all were spouses) was conducted using Pittsburgh Sleep Quality Index, Zung's self-rating depression and anxiety scales, Parkinson's Impact Scale (PIMS) (only for PD), and an additional sleep questionnaire. RESULTS: Eighty-four percent of patients were 'poor sleepers' with global sleep scores (GLSc) > 5. Other abnormalities were: excessive daytime sleepiness-57.5%, excessive daytime fatigue-72.5%, depression-51.5%, anxiety-63.1%, and abnormal PIMS score-83.8%. There was no correlation between the degree of sleep dysfunction and the age, severity, duration of PD or its treatment. Several component sleep scores correlated with anxiety scores, PIMS score with depression, and, subjects with GLSc > or = 10 had higher mean anxiety index. Daytime dysfunction (97.5%) was mainly associated with reduced enthusiasm, rather than excessive sleepiness. Among CG, 40% had a GLSc > 5, 21% had depression, and 10.5% had anxiety. Their depression, anxiety and sleep scores correlated with those of their spouses. CONCLUSIONS: PD patients with significant SD may represent a subset of patients with early, progressive degeneration of sleep centres, rather than an enhanced aging process. They are more susceptible mood disturbances, which correlate with the severity of sleep dysfunction. Sleep and mood disturbances also adversely affect the quality of life of spousal caregivers.

Familial and sporadic Parkinson's disease usually display the same clinical features.

We examined the clinical features of familial (n = 26) and sporadic (n = 52) Parkinson's disease (PD) in patients presenting over the age of 40 years. Familial PD cases were tested for alpha-synuclein or parkin mutations as appropriate. No mutations were found in any of the families investigated. We found no between-group differences in the age at onset of PD, the pattern or severity of parkinsonian features, the dose of antiparkinsonian medications or treatment related complications. Cases of familial and sporadic PD in our cohort of patients display similar clinical features. This may suggest similar etiologies for both familial and sporadic PD.

Positron emission tomography of dopamine pathways in familial Parkinsonian syndromes.

Positron emission tomography (PET) scan is considered to be the most useful tool with which to assess the integrity of nigrostriatal function in the living brain. Recently, different genetic defects have been associated with a variety of familial parkinsonian syndromes, the clinical phenotypes of which have varying degrees of similarities to idiopathic parkinsonism (IP), (sporadic Parkinson's disease). This review summarizes: (1) the PET scan findings (fluorodopa uptake and raclopride binding) in both familial parkinsonian syndromes and IP; and (2) the similarities and differences of the clinical and PET features between familial parkinsonian syndromes and IP. This analysis demonstrates that more similarities than differences exist in PET scan findings in the different familial parkinsonian syndromes with the exception of pallido-ponto-nigral degeneration (PPND), that is perhaps best considered as multisystem degeneration. As a result of this analysis, we believe that while different genetic defects may underlie different mechanisms of nigrostriatal degeneration, the final pattern of nigrostriatal dysfunction is essentially similar to that of IP. 'Parkinson's disease', therefore, may not represent a single disease entity, but rather the final manifestation of different pathogenetic mechanisms-mediated by genetic or environmental factors, or an interaction of genetic and environmental factors.

Daytime somnolence in patients with Parkinson's disease.

We studied daytime sleepiness in 160 patients with Parkinson's disease and 40 normal subjects. We compared the prevalence of daytime sleepiness in patients who were taking levodopa alone, levodopa with bromocriptine, levodopa with ropinirole, and levodopa with pramipexole. We found that (1) all these anti-Parkinson drugs can cause daytime sleepiness; (2) 'dozing off' correlated highly with 'falling asleep without warning'; (3) after statistical adjustment for confounding variables there was no significant difference among the risks for any of these anti-Parkinson drugs causing daytime somnolence.

Botulinum toxin A as treatment for drooling saliva in PD.

The authors evaluated intraparotid injections of botulinum toxin A in reducing salivary secretions and drooling in nine patients with PD. There was a marked objective reduction in secretion, and two thirds of the patients had subjective improvement in drooling. No side effects were observed. The authors conclude that botulinum toxin A promises to be a simple and effective treatment for the common problem of drooling saliva in chronic neurologic disease.

A review of normal sleep and its disturbances in Parkinson's disease.

Patients with Parkinson's disease frequently report sleep disturbances which include difficulty initiating or maintaining sleep, parasomnias or excessive daytime sleepiness. The underlying causes include: normal aging, motor symptoms of the disease, antiparkinson drugs, comorbid psychiatric conditions, and concurrent illnesses. An accurate history from the patient and care-giver regarding previous sleep patterns and how they have changed, and the degree of impact these sleep disturbances have on patient's daily life is crucial for successful management. Apart from drug therapy, appropriate counselling and nonpharmacologic treatments have major roles in the overall management. This review summarizes the current concepts of (i) the pattern and function of normal sleep, and (ii) the nature, pathogenesis and management of sleep disturbances in Parkinson's disease.

Validating a quality of life rating scale for idiopathic parkinsonism: Parkinson's Impact Scale (PIMS).

The signs and symptoms of idiopathic parkinsonism (IP, Parkinson's disease) are most commonly documented using one or more rating scales that assess physical limitations due to illness and drug side-effects with some attention being paid to depression. Scant attention has been paid to the impact of these limitations on a patient's life. Nurses in the Parkinson Foundation of Canada Clinical Assistance/ Outreach Programmes have designed a Quality of Life Rating Scale (Parkinson's Impact Scale, PIMS) to measure the impact of IP on 10 aspects of a patient's emotional, social and economic life. The scale had to fit onto one side of an 8 x 11 in. piece of paper, take a patient less than 10 min to complete, take fluctuations in symptoms ('on/off' attacks) into account, have unambiguous guidelines for the definition of each item, and a simple scoring system. A study was carried out to assess the reliability and validity of the scale. Nurses in nine Movement Disorder Clinics and one Outreach Programme participated. A total of 167 patients were asked to use the scale on three separate occasions, 1 month apart, without referring to the scores they had assigned to the scale in the previous month. Factor analysis identified four factors among the items in the scale: psychological, social, physical and financial. Internal consistency was 89.8% and the test-retest reliability was 72%. Construct validity was assessed by comparing factor scores and a global score between non-fluctuating patients and fluctuating patients in their 'off' state. The scores were significantly higher in the more severe 'off' state (p < 0.0001).

Patterns of asymmetry do not change over the course of idiopathic parkinsonism: implications for pathogenesis.

We investigated the asymmetry of focal deficits of bradykinesia in a cross-sectional study of 198 patients with idiopathic parkinsonism. We have analyzed the difference in Unified Parkinson's Disease Rating Scale (UPDRS) scores between the more and less affected sides in these patients, whose duration of symptoms ranged from 1 to 15 years. There was no significant change in the asymmetry or focality over this period; the deficit for each side progressed faster initially and then approached the normal age-related linear rate of decline. Previous studies indicate that there is an inverse linear relation between the UPDRS bradykinesia score and the nigral dopaminergic cell count. We infer that the rate of death of nigral dopaminergic neurons is predetermined from the time of onset of pathogenesis. The simplest explanation is that a causal event kills some cells and damages others so that they undergo premature death. This sequence of changes could be implemented through environmental (toxic or viral) damage to the genome. Several diverse sources of evidence support this concept.

New immunosuppressive reagents to aid the induction of tolerance in organ graft recipients.

Thirty years ago when the first immunosuppressive agents became available for clinical grafting, the procedure was regarded with great skepticism by the medical profession as a pastime for ignorant surgeons with results that at best were poor. With the introduction of cyclosporin 15 years ago, the results of organ transplantation improved, and for the first time it was possible to transplant lung and pancreas with a reasonable outcome. Now more than 200,000 organ grafts have been performed worldwide and the procedure is an important established part of therapeutic surgery.

Clinical observations on the rate of progression of idiopathic parkinsonism.

The time course of evolution of clinical deficits has been a traditional guide to the nature of the aetiopathogenesis of neurological disease. We studied the influence of ageing and duration of disease on the natural history of idiopathic parkinsonism (IP). Two hundred and thirty-eight patients with IP were examined while off medication. Bradykinesia scores were analysed against patients' age and duration of disease by multiple regression. There was no significant interaction between the effects of age and of duration (P = 0.923). We conclude that age and duration of symptoms influence the natural history of IP additively and independently. Furthermore, the rate of neuronal death is more rapid in the earlier stages of evolution of the pathology; subsequently, the velocity of progression slows down to approach the rate of attrition produced by normal ageing. This time course has implications for possible models of pathogenesis.

Nursing care of patients with idiopathic parkinsonism.

Through the discussion of the work of a movement disorder clinic in British Columbia, this paper focuses on the unique contribution of nursing care in the effective management of idiopathic parkinsonism. It follows on from a paper discussing the aetiology and treatment of the disease published on April 20 in Nursing Times.

Examining causes and care of idiopathic parkinsonism.

This year marks the 25th anniversary of the Parkinson's Disease Society in Britain. This paper looks at the aetiology and treatment of idiopathic parkinsonism and, through discussion of the work of a movement disorder clinic in British Columbia, focuses on the unique contribution of nursing care to effective management of the condition. 'Idiopathic parkinsonism' is used to describe parkinsonism of unknown aetiology. This term is preferable to 'Parkinson's disease' before identification of the cause. This position is forcefully endorsed by patient groups who eschew the term 'disease'.

Dehumanisation in intensive care.

This paper examines the concept of dehumanisation in relation to the experience of the critically ill patient. It focuses on the effect of critical illness on an individual's self-identity and the influence this has on the nurse's ability to provide person-centered care in ICU.

Artificial ventilation and chest compression.

This paper examines the rationale for actions taken by health-care professionals when managing adult patients who have had a cardiorespiratory arrest in hospital. The focus is on aspects of ventilation and chest compression, which are key features of cardiopulmonary resuscitation.

Tendon jerks in Parkinson's disease.

Tendon reflexes were examined in 119 patients with idiopathic parkinsonism (IP) and 40 spouse controls to estimate the type and frequency of any alterations in the reflexes. Forty one of 119 patients and 2 of 40 controls had reflex ratings of 3+ at two or more sites (p < 0.001). There was no correlation of reflex score with the severity of disease or with the cardinal signs of IP. In 21 patients with asymmetric tendon jerks the side with the more active reflexes correlated with the side with greater parkinsonian signs. We conclude that an increase in tendon jerks is a feature of IP. The pathophysiology of this change in reflexes should be investigated further to establish if it is a heretofore overlooked manifestation of basal ganglia dysfunction or a link with other neurodegenerative diseases.