Progression of Neuropsychiatric Symptoms over Time in an Incident Parkinson's Disease Cohort (ICICLE-PD).

BACKGROUND: Cross-sectional studies have identified that the prevalence of neuropsychiatric symptoms (NPS) in Parkinson's disease (PD) ranges from 70-89%. However, there are few longitudinal studies determining the impact of NPS on quality of life (QoL) in PD patients and their caregivers. We seek to determine the progression of NPS in early PD. METHODS: Newly diagnosed idiopathic PD cases (n = 212) and age-matched controls (n = 99) were recruited into a longitudinal study. NPS were assessed using the Neuropsychiatric Inventory with Caregiver Distress scale (NPI-D). Further neuropsychological and clinical assessments were completed by participants, with reassessment at 18 and 36 months. Linear mixed-effects modelling determined factors associated with NPI-D and QoL over 36 months. RESULTS: Depression, anxiety, apathy and hallucinations were more frequent in PD than controls at all time points (p < 0.05). Higher motor severity at baseline was associated with worsening NPI-D scores over time (ß = 0.1, p < 0.05), but not cognition. A higher NPI total score was associated with poorer QoL at any time point (ß = 0.3, p < 0.001), but not changed in QoL scores. CONCLUSION: NPS are significantly associated with poorer QoL, even in early PD. Screening for NPS from diagnosis may allow efficient delivery of better support and treatment to patients and their families.

Prevalence and duration of non-motor symptoms in prodromal Parkinson's disease.

BACKGROUND AND PURPOSE: The prevalence and duration of non-motor symptoms (NMS) in prodromal Parkinson's disease (PD) has not been extensively studied. The aim of this study was to determine the prevalence and duration of prodromal NMS (pNMS) in a cohort of patients with recently diagnosed PD. METHODS: We evaluated the prevalence and duration of pNMS in patients with early PD (n = 154). NMS were screened for using the Non-Motor Symptom Questionnaire (NMSQuest). We subtracted the duration of the presence of each individual NMS reported from the duration of the earliest motor symptom. NMS whose duration preceded the duration of motor symptoms were considered a pNMS. Individual pNMS were then grouped into relevant pNMS clusters based on the NMSQuest domains. Motor subtypes were defined as tremor dominant, postural instability gait difficulty (PIGD) and indeterminate type according to the Movement Disorder Society Unified Parkinson's Disease Rating Scale revision. RESULTS: Prodromal NMS were experienced by 90.3% of patients with PD and the median number experienced was 4 (interquartile range, 2-7). A gender difference existed in the pNMS experienced, with males reporting more sexual dysfunction, forgetfulness and dream re-enactment, whereas females reported more unexplained weight change and anxiety. There was a significant association between any prodromal gastrointestinal symptoms [odds ratio (OR), 2.30; 95% confidence interval (CI), 1.08-4.89, P = 0.03] and urinary symptoms (OR, 2.54; 95% CI, 1.19-5.35, P = 0.016) and the PIGD phenotype. Further analysis revealed that total pNMS were not significantly associated with the PIGD phenotype (OR, 1.10; 95% CI, 0.99-1.21, P = 0.068). CONCLUSIONS: Prodromal NMS are common and a gender difference in pNMS experienced in prodromal PD may exist. The PIGD phenotype had a higher prevalence of prodromal gastrointestinal and urinary tract symptoms.

Cerebral glucose metabolism and cognition in newly diagnosed Parkinson's disease: ICICLE-PD study.

OBJECTIVE: To assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive decline. METHODS: FDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA. RESULTS: PD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (ß=0.38, p=0.001) and MoCA (ß=0.3, p=0.002) at 18 months controlling for baseline score. CONCLUSIONS: Reductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia.

Cognitive impairment in Parkinson's disease: impact on quality of life of carers.

BACKGROUND: The quality of life (QoL) of informal caregivers of people with Parkinson's disease (PD) (PwP) can be affected by the caring role. Because of cognitive symptoms and diminished activities of daily living, in addition to the management of motor symptoms, carers of PwP and cognitive impairment may experience increased levels of burden and poorer QoL compared with carers of PwP without cognitive impairment. This study aimed to investigate the impact of cognitive impairment in PD upon QoL of carers. METHODS: Approximately 36 months after diagnosis, 66 dyadic couples of PwP and carers completed assessments. PwP completed a schedule of neuropsychological assessments and QoL measures; carers of PwP completed demographic questionnaires and assessments of QoL. Factor scores of attention, memory/executive function and global cognition, as derived by principal component analysis, were used to evaluate cognitive domains. RESULTS: Hierarchical regression analysis found lower Montreal Cognitive Assessment was a significant independent predictor of poorer carer QoL, in addition to number of hours spent caregiving, carer depression and PD motor severity. Attentional deficits accounted for the largest proportion of variance of carer QoL. Carers of PwP and dementia (n = 9) had significantly poorer QoL scores compared with PwP and mild cognitive impairment (n = 18) or normal cognition (n = 39) carers (p < 0.01). CONCLUSIONS: Attentional deficits were the strongest predictor of carer QoL compared with other cognitive predictors. Carers for those with PD dementia reported the poorest QoL. Interventions such as respite or cognitive behavioural therapy to improve mood and self-efficacy in carers may improve carer QoL. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd.

Ethics and care for older people approaching the end of life -- symptoms, choices and dilemmas.

The provision of high quality care to older people with complex healthcare needs brings a unique set of clinical and ethical issues. This symposium explored a range of challenging topics which often confront clinicians. It aimed to increase knowledge of symptom control in complex conditions, improve confidence in decision-making regarding difficult ethical situations, and to provide a better understanding of how to organise and support end of life care both in the hospital and in the community.

Head-up Tilt Table Testing: a state-of-the-art review.

Vasovagal syncope (VVS) is the commonest cause of syncope accounting for up to 60% of all cases. The head-up tilt-table test (HUTT) was first described as a diagnostic test for VVS in 1986 and is now in widespread use as a research and diagnostic tool. Vasovagal syncope was previously thought to be confined to younger patients but with the introduction of HUTT, it is now being diagnosed with greater frequency in the elderly. Research into the physiological changes in susceptible individuals during HUTT has greatly increased our understanding of the pathophysiological processes underlying VVS; in particular, the hypotensive response during VVS is associated with sympathetic withdrawal rather than bradycardia alone. Various provocation agents, including nitrates, isoprotenerol and lower body negative pressure have been described to improve the diagnostic yield of the HUTT. Glyceryl trinitrate is now routinely administered during HUTTs. Individuals with typical presentations and infrequent episodes do not require investigation with HUTT as history alone is often diagnostic. The head-up tilt-table test is, however, required with atypical features, seizure activity, occupational issues, and is more likely to be required in older patients. The practicalities of conducting the HUTT and limitations of HUTTs are also discussed.

Perinatal and maternal risk factors for autism spectrum disorders in New South Wales, Australia.

BACKGROUND: This study was commenced in 1999 with the aim of examining risk factors for autism using established population-based data for comparison. METHODS: Cases were ascertained using active surveillance and compared with birth data. RESULTS: Four risk factors were found to be significantly associated with autism using binary logistic regression analysis; being male [adjusted odds ratio (OR) 4.7, 95% confidence interval (CI) 3.2-7.0], being born prematurely (adjusted OR 2.2, 95% CI 1.5-3.5), having maternal age >/=35 years (adjusted OR 1.7, 95% CI 1.2-2.4) and having a mother born outside Australia (adjusted OR 1.4, 95% CI 1.0-1.9). For analysis completed for pregnancies, rather than live births, multiple birth was also a significant risk factor for one or more children of the pregnancy to be affected by autism (adjusted OR 2.5, 95% CI 1.1-5.5). There was a statistically significant trend towards increasing risk with increasing risk factor 'dose' for gestational age (P = 0.019), multiple birth (P = 0.016) and maternal age (P < 0.001). For mother's country of birth the group with the highest risk were children of mother's born in south-east or north-east Asia. There was a non-significant trend towards a higher proportion of children with developmental disability having risk factors. CONCLUSION: Replication of risk factors from previous studies and a significant risk factor 'dose' effect add to growing evidence that maternal and perinatal factors are low magnitude risk factors for autism. The association between developmental disability and autism risk factors warrants further examination.

Collaborative research and development on mifepristone in China to reduce unwanted pregnancies and recourse to abortion.

A program proposed and executed by The Concept Foundation and funded by the Rockefeller Foundation demonstrates the feasibility of using private/public-sector collaboration for making mifepristone widely available. The application of mifepristone to emergency, luteal phase and menstrual induction contraception is being assessed in clinical research programs conducted in accordance with international standards for good clinical research. Opportunities for introduction of mifepristone in developing countries are being pursued using mifepristone produced in China in accordance with international standards of good manufacturing practice.

Stroke prevention in non-rheumatic atrial fibrillation.

Warfarin can strikingly prevent stroke in patients with NRAF with or without a history of stroke or TIA. The target degree of anticoagulation is an INR between 2.0 and 3.0. Any degree of anticoagulation with less than an INR of 2.0 will not provide full protection, any greater anticoagulation is no more effective, and an INR greater than 4.0 increases the risk of hemorrhage. Patients 65 years or younger without any risk factor do no better with warfarin than with aspirin or placebo, and should not be anticoagulated. All older patients or those with risk factors but without contraindications gain significant stroke prevention with warfarin anticoagulation as recommended above.

Posterior cerebral artery stenosis with midbrain infarction.

BACKGROUND: Brain infarction secondary to stenosis of the posterior cerebral artery is uncommon. We report a patient with midbrain infarction and symptoms of both Benedikt's and pupil-sparing oculomotor palsy syndromes secondary to posterior cerebral artery stenosis. CASE DESCRIPTION: A 51-year-old woman developed diplopia, left ptosis, and right hemiataxia and hyperactive tendon reflexes. Pupils were equal and reactive. Radiological examination revealed stenosis of the posterior cerebral artery and left-sided midbrain infarct. CONCLUSIONS: Stenosis of the posterior cerebral artery may cause only midbrain infarction and may be responsible for Benedikt's and pupil-sparing oculomotor palsy syndromes.

Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-l-histidyl-l-lysine copper.

A multicenter, randomized, evaluator-blinded, placebo-controlled clinical study was conducted to evaluate the safety and effectiveness of glycyl-l-histidyl-l-lysine: copper complex (lamin Gel) in the treatment of diabetic neuropathic ulcers. All patients were enrolled in an aggressive standardized wound care protocol consisting of sharp debridement at study entry, daily application of a metered dose of drug, standardized pressure-relieving footwear, and patient education relating to diabetes control and activity modifications. Treatment with lamin Gel significantly increased the percentage of closure of plantar ulcers (98.5% median area percentage closure compared with 60.8% for vehicle; p < 0.05) and the proportion of patients healing 98% or better. The rate of closure was three times faster with lamin Gel treatment compared with standard care and vehicle. The enhancement of wound closure was more pronounced (median of 89.2% compared with -10.3% for vehicle; p < 0.01) in larger (greater than 100 mm(2) initial area at study entry) plantar ulcers caused by the failure of this size of ulcer to respond adequately to standardized wound care treatments in the absence of lamin Gel. Treatment must commence immediately after the initial wound debridement to obtain optimal enhancement of the ulcer closure. The incidence of ulcer infections was significantly lower (7% incidence compared with 34% for vehicle, p < 0.05) in the plantar ulcers treated immediately after debridement with the lamin Gel.

Collagen and prostaglandin synthesis in force-stressed periodontal ligament in vitro.

A periodontal organ culture system capable of receiving orthodontic type forces was developed. Histological, radioautographical, collagen, and prostaglandin synthetic data demonstrated the vitality of the organ over a 24-hour period of culture. Significant increases in the proportion of type III collagen synthesized during periods of active stress were found, but no alterations in relative levels of prostaglandins synthesized during periods of force application were discernible.

Word deafness in Wernicke's aphasia.

Three patients with otherwise typical Wernicke's aphasia showed consistent superiority of visual over auditory comprehension. The precedents for and anatomical basis of a selective auditory deficit in Wernicke's aphasia are discussed, including the relationship to pure word deafness. One implication of spared visual language function may be the use of gesture in language therapy for such patients.

Hemophilus influenzae type B, mediastinitis, cellulitis, bacteremia, and meningitis in an adult.

A 63-year-old woman presented with cellulitis of the upper anterior chest and neck that rapidly extended into an acute mediastinitis. Pleural effusions and meningitis subsequently developed. The infection was due to an ampicillin-susceptible strain of Hemophilus influenzae type B. The patient was treated with and responded to chloramphenicol therapy. No definite predisposing factor could be determined.

Cervical bruits in hemodialysis patients.

Twenty-five patients receiving chronic hemodialysis were studied with systematic cervical auscultation and periorbital Doppler tests to determine the incidence of cervical bruits and their significance. Eighteen (72%) of the patients had bruits. All of the bruits heard in this study were loudest in the supraclavicular fossa, and in no patient was a bruit heard along the carotid arteries without a louder bruit of similar characteristics more proximally. No patient with a bruit in the area of the carotid bifurcation had an abnormal ipsilateral periorbital Doppler examination, and none had symptoms of cerebral ischemia. There was no evidence in these patients that the bruits were related to occlusive arterial disease. It is concluded that most cervical bruits in patients receiving hemodialysis are the result of a hyperdynamic circulatory state associated with anemia and arteriovenous fistulae.

Angiographic appearance of carotid occlusion in acute stroke.

The angiographic appearance of the proximal end of internal carotid artery occlusion is reported in 41 patients with acute stroke in the areas of the brain supplied by the carotid artery. All patients had angiography within 6 days of stroke onset, the majority within 24--48 hours. Three angiographic configurations of internal carotid occlusion were found, in descending order of frequency: a sharp, pointed stump; virtual absence of the artery; and a rounded, blunt stump. The results suggest that the angiographic appearance of the proximal occlusion alone may not accurately predict the age of the occlusion within the first 6 days from stroke onset.

Mechanisms of acute carotid stroke.

In a three-year study, the clinical course and results of intracranial angiography were compared in patients having an acute stroke in the carotid artery territory combined with angiographic abnormalities indicating severe extracranial carotid stenosis or occlusion. Two major mechanisms of stroke were delineated. In one group, the angiographic intracranial abnormalities strongly suggested the presence of embolism in the cerebral vessels supplied by the stenotic or occluded carotid artery; many of these patients had no obvious transient ischemic attacks prior to their stroke and experienced a moderate to severe clinical deficit. In the other group, evidence of embolism was absent; many showed a widespread delay in cerebral arterial perfusion, experienced a greater frequency of transient ischemic attacks before their stroke, and had a milder stroke than did those with embolism.