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Background: Psychiatric symptoms are a common feature of Huntington’s disease (HD) and often precede the onset of motor and cognitive impairments. However, it remains unclear whether psychiatric changes in the preclinical period result from structural change, are a reaction to being at risk or simply a coincidental occurrence. Few studies have investigated the temporal course of psychiatric disorder across the preclinical period. Objectives: To compare lifetime and current prevalence of psychiatric disorder in presymptomatic gene carriers and non-carriers and to examine the relationship of psychiatric prevalence in gene carriers to temporal proximity of clinical onset. Methods: Lifetime and current psychiatric histories of 204 at risk individuals (89 gene carriers and 115 non-carriers) were obtained using a structured clinical interview, the Composite International Diagnostic Interview. Psychiatric disorders were classified using both standardised diagnostic criteria and a more subtle symptom based approach. Follow-up of gene carriers (n = 51) enabled analysis of the role of temporal proximity to clinical onset. Results: Gene carriers and non-carriers did not differ in terms of the lifetime frequency of clinical psychiatric disorders or subclinical symptoms. However, gene carriers reported a significantly higher rate of current depressive symptoms. Moreover, the rate of depression increased as a function of proximity to clinical onset. Conclusions: Affective disorder is an important feature of the prodromal stages of HD. The findings indicate that depression cannot be accounted for by natural concerns of being at risk. There is evidence of a window of several years in which preclinical symptoms are apparent.

Objective: To characterise the clinical features of non-familial migraine with unilateral motor symptoms (MUMS) and compare these features with those of migraine without weakness. Methods: 24 patients with MUMS and 48 matched controls were identified from a tertiary care headache centre. Using a structured interview, the migraine symptoms of both groups were characterised. Results of previously administered Beck Depression Inventories (BDI), Minnesota Multiphasic Personality Inventories and psychiatric diagnoses were collected, when available, and compared between groups. Results: 9 patients had episodic migraine and 15 had chronic migraine. Patients with MUMS always had weakness involving the arm subjectively, and both arm and leg objectively. A give-way character was always present. Only 17% of patients with MUMS reported facial weakness; 58% reported persistent interictal weakness; 92% reported sensory symptoms. A rostrocaudal march of sensory and motor symptoms was frequently reported. Weakness was ipsilateral to unilateral headache in two thirds of the patients. Compared with controls, patients with MUMS had had similar pain intensities, but were more likely to report other migrainous symptoms, including allodynia. 38% of patients with MUMS were told they had had a stroke, and 17% believed they had had a stroke despite normal brain imaging. Patients with MUMS reported fewer affective disorders and more adjustment disorders than controls, and had similar BDI scores. Conclusions: A syndrome of severe migraine with accompanying give-way weakness is common in tertiary care headache centres. It is accompanied by other neurological symptoms.

Objective: To explore the profile of neuropsychiatric symptoms in patients with dementia associated with Parkinson’s disease (PDD). Methods: 537 patients with PDD drawn from an international multicentre clinical trial of rivastigmine were assessed using the 10-item Neuropsychiatric Inventory (NPI). A cluster analysis was used to investigate the inter-relationship of NPI items. Associations between the clusters and demographic and clinical variables were analysed. Results: 89% of the patients presented at least one symptom on the NPI, 77% had two or more symptoms and 64% had at least one symptom with a score ⩾4. The most common symptoms were depression (58%), apathy (54%), anxiety (49%) and hallucinations (44%). Patients with more severe dementia and advanced Parkinson’s disease had more neuropsychiatric symptoms. Nearly 60% of the care givers reported at least one NPI symptom to be of at least moderate severe distress. Five NPI clusters were identified: one group with few and mild symptoms (52%); a mood cluster (11%, high scores on depression, anxiety and apathy); apathy (24%; high apathy and low scores on other items); agitation (5%, high score on agitation and high total NPI score); and a psychosis cluster (8%; high scores on delusions and hallucinations). The psychosis and agitation clusters had the lowest Mini-Mental State Examination score and the highest Unified Parkinson’s Disease Rating Scale and care giver distress scores. Conclusion: Neuropsychiatric symptoms are common in patients with PDD. The profile of these symptoms differs from that in other types of dementia. Subgroups with different neuropsychiatric profiles were identified. These subgroups may be associated with distinct neurobiological changes, which should be explored in future studies.

Objectives: To examine the development of nocturnal sleeping problems in patients with Parkinson’s disease (PD) over an 8-year period and to study the clinical and demographic correlates of insomnia. Methods: 231 patients were included in a population-based prevalence study in 1993, and re-examined in 1997 and 2001. At all study visits, we applied semi-structured interviews to obtain information on clinical and demographic data, as well as on nocturnal sleeping problems. Standardised rating scales of parkinsonism, depression and cognitive impairment were used. The relationship between insomnia and demographic and clinical variables was analysed using population-averaged logistic regression models for correlated data. 231 patients were included at baseline, 142 were available for re-evaluation in 1997 and 89 patients in 2001. Results: Most nocturnal sleeping problems varied little in prevalence over time, whereas problems related to turning in bed and vivid dreaming or nightmares increased. Insomnia was present in 54–60% of the patients at each of the three study visits and varied considerably in individual patients over time. The presence of insomnia was closely related to disease duration, higher Montgomery–Asberg Depression Rating Scale scores and female sex. Conclusion: Insomnia is a highly frequent complaint in patients with PD. It fluctuates over time in individual patients, and its origin seems to be multifactorial. Physicians should be aware of the high prevalence of insomnia in patients with PD and should examine their patients for a possible coexisting depression.

Objective: To determine the earliest symptoms of anosognosia in people with Alzheimer’s disease and to validate a criteria-guided strategy to diagnose anosognosia in dementia. Methods: A consecutive series of 750 patients with very mild or probable Alzheimer’s disease attending a memory clinic, as well as their respective care givers, was assessed using a comprehensive psychiatric evaluation. Results: The factors of anosognosia for (1) basic activities of daily living (bADL), (2) instrumental activities of daily living (iADL), (3) depression and (4) disinhibition were produced by a principal component analysis on the differential scores (ie, caregiver score minus patient score) on the anosognosia questionnaire for dementia. A discrepancy of two or more points in the anosognosia-iADL factor was found to have a high sensitivity and specificity to identify clinically diagnosed anosognosia in people with Alzheimer’s disease. By logistic regression analysis, the severity of dementia and apathy were both shown to be noticeably associated with anosognosia in people with Alzheimer’s disease. Conclusion: Anosognosia in those with Alzheimer’s disease is manifested as poor awareness of deficits in iADL and bADL, depressive changes and behavioural disinhibition. The frequency of anosognosia is found to increase considerably with the severity of dementia. The validity of a specific set of criteria to diagnose anosognosia in people with Alzheimer’s disease was shown, which may contribute to the early identification of this condition.

Apathy and depression are the most frequent behavioural and psychiatric disorders in Alzheimer's disease, and may both have a negative impact on the progression of the illness.To examine the clinical correlates of apathy in Alzheimer's disease (AD), and to determine whether apathy is a significant predictor of more rapid cognitive, functional and emotional decline.Using a structured psychiatric evaluation, we examined a consecutive series of 354 subjects meeting clinical criteria for AD. Apathy was assessed by the Apathy Scale, and diagnosed using standardised criteria. Additional measurements included scales for depression, functional impairment, and global cognitive functions. A follow up evaluation was carried out in 247 patients (70% of the total sample) between 1 and 4 years after the baseline evaluation.Apathy was significantly associated with older age (p = 0.009), and a higher frequency of minor and major depression (p0.0001). Apathy at baseline was a significant predictor of depression at follow up (p = 0.01), and was associated with a faster cognitive (p = 0.0007) and functional decline (p = 0.006).Apathy in AD is a behavioural marker of a more aggressive dementia, characterised by a faster progression of cognitive, functional, and emotional impairment.

Background: Fatigue is a major complaint of multiple sclerosis (MS) patients. However, little is known about its pathophysiological mechanisms. Evidence from chronic fatigue syndrome and studies on sickness behaviour suggest that immune and neuroendocrine factors may play a causative role in the development of fatigue. Methods: We compared whole blood stimulatory capacity for pro- (TNFα, IFNγ) and anti-inflammatory cytokines (IL-10) as well as hypothalamo-pituitary-adrenal (HPA) axis function in 15 MS patients with marked fatigue and 15 patients without fatigue as determined by the Fatigue Severity Scale (FSS). Results: Proinflammatory cytokines were significantly higher (TNFα: 478.9 v 228.2 pg/ml, p = 0.01; IFNγ: 57.6 v 27.8 pg/ml; p = 0.01) in MS patients with fatigue. Furthermore, TNFα values significantly correlated with daytime sleepiness as measured by the Epworth Sleepiness Scale (r = 0.64, p = 0.001). Controlling for disease activity (as measured by the Cambridge Multiple Sclerosis Basic Score), disease duration, Expanded Disability Status Scale, and depression further increased the correlation of cytokine production and fatigue. HPA axis activity was not related to fatigue but was modestly correlated with cognitive impairment. Conclusion: Our data suggest that fatigue in MS is at least partially mediated through activation of proinflammatory cytokines. In line with earlier findings, HPA axis dysfunction seems not to be relevant in MS fatigue pathogenesis but appears to be linked to cognitive impairment. Our findings suggest that increased levels of inflammatory cytokines may be involved in MS fatigue. Investigation of cytokine profiles may increase the understanding of fatigue pathogenesis in MS.

Background: The short term benefits of bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced levodopa responsive Parkinson's disease (PD) are well documented, but long term benefits are still uncertain. Objectives: This study provides a 5 year follow up of PD patients treated with stimulation of the STN. Methods: Thirty seven consecutive patients with PD treated with bilateral STN stimulation were assessed prospectively 6, 24, and 60 months after neurosurgery. Parkinsonian motor disability was evaluated with and without levodopa treatment, with and without bilateral STN stimulation. Neuropsychological and mood assessments included the Mattis Dementia Rating Scale, the frontal score, and the Montgomery-Asberg Depression Rating Scale (MADRS). Results: No severe peri- or immediate postoperative side effects were observed. Six patients died and one was lost to follow up. Five years after neurosurgery: (i) activity of daily living (Unified Parkinson Disease Rating Scale (UPDRS) II) was improved by stimulation of the STN by 40% ("off" drug) and 60% ("on" drug); (ii) parkinsonian motor disability (UPDRS III) was improved by 54% ("off" drug) and 73% ("on" drug); (iii) the severity of levodopa related motor complications was decreased by 67% and the levodopa daily doses were reduced by 58%. The MADRS was unchanged, but cognitive performance declined significantly. Persisting adverse effects included eyelid opening apraxia, weight gain, addiction to levodopa treatment, hypomania and disinhibition, depression, dysarthria, dyskinesias, and apathy. Conclusions: Despite moderate motor and cognitive decline, probably due to disease progression, the marked improvement in motor function observed postoperatively was sustained 5 years after neurosurgery.

Background: Whereas apathy is increasingly recognised as a frequent abnormal behaviour in dementia, its overlap with depression remains poorly understood. Aims: To assess the psychometric characteristics of a structured interview for apathy, and to examine the overlap between apathy and depression in dementia. Methods: A total of 150 patients with Alzheimer’s disease (AD) underwent a comprehensive psychiatric and cognitive assessment. Results: Twelve per cent of the sample met criteria for both apathy and depression, 7% met criteria for apathy only, and 31% met criteria for depression only. Apathy (but not depression) was significantly associated with more severe cognitive deficits. Apathy and anxiety scores accounted for 65% of the variance of depression scores in dementia, and the diagnosis of apathy had a minor impact on the rating of severity of depression. Conclusions: The Structured Interview for Apathy demonstrated adequate psychometric characteristics. Using a novel structured interview for apathy in AD we demonstrated that whereas the construct of depression primarily consists of symptom clusters of apathy and anxiety, apathy is a behavioural dimension independent of depression.

Objectives: To characterise the clinical features, emergency pre-paediatric intensive care (PIC) treatment, and course of status epilepticus (SE) in children admitted to PIC. This may provide insight into reasons for admission to PIC and provide a framework for the development of strategies that decrease the requirement for intensive care. Design: Cross sectional, retrospective study. Setting: A tertiary paediatric institution's intensive care unit. Participants: The admission database and all discharge summaries of each admission to a tertiary paediatric institution's PIC over a three year period were searched for children aged between 29 days and 15 years with a diagnosis of SE or related diagnoses. The case notes of potential cases of SE were systematically reviewed, and clinical and demographic data extracted using a standard data collection form. Results: Most children with SE admitted to PIC are aged less than 5 years, male to female ratio 1:1, and most (77%) will have had no previous episodes of SE. Prolonged febrile convulsions, SE related to central nervous system infection, and SE associated with epilepsy occur in similar proportions. Contrary to the Advanced Paediatric Life Support guidelines many children admitted to PIC for SE receive over two doses, or inadequate doses, of benzodiazepine. There is a risk of respiratory depression following administration of over two doses of benzodiazepine (χ2 = 3.4, p = 0.066). Children with SE admitted to PIC who had prehospital emergency treatment are more likely to receive over two doses of benzodiazepines (χ2 = 11.5, p = 0.001), and to subsequently develop respiratory insufficiency (χ2 = 6.2, p = 0.01). Mortality is low. Further study is required to determine the morbidity associated with SE in childhood requiring intensive care. Conclusions: As the risk of respiratory depression is greater with more than two doses of benzodiazepines, clinicians should not disregard prehospital treatment of SE. As pre-PIC treatment of SE is inadequate in many cases, appropriate audit and modifications of standard guidelines are required.

Objectives: To evaluate functioning, 18 months after surgery, of 49 patients with good neurological recovery following aneurysmal subarachnoid haemorrhage (SAH), and to determine the extent of any improvements in disturbances of mood, cognitive functioning, and levels of activity and participation previously observed at 9 month follow up. Methods: SAH patients, matched for age, gender, and occupation with healthy control participants, completely quantitative measures of mood (HADS, FIES, BDI) and activity/participation (BICRO-39 scales), and a brief cognitive assessment battery (verbal fluency, digit span, prose recall). Controls completed the HADS and the BICRO-39. Results: Patients showed some recovery of cognitive functioning, though impairments of prose recall persisted. Anxiety and depression symptoms were higher in patients than in controls, but fewer than 20% scored in the clinical range on any questionnaires except for RIES-Intrusive thoughts (22%); only three showed signs of full blown post-traumatic stress disorder. Almost half showed elevated dependence on others for domestic activities and organisation and abnormally low levels of employment. Very little variance in outcome was predicted by demographic variables, neurological or cognitive impairment, prior life stress, or mood. However, levels of social activity and self-organisation were related to persisting fatigue. Conclusions: The observed decline in intrusive thoughts and avoidance over time is consistent with that seen after life threatening illness or trauma. The persistent reductions in independence and levels of employment may in some cases reflect considered lifestyle adjustments rather than adverse and unwanted changes but in others indicate a need for focused rehabilitation.

Background: Evidence from epidemiological and neuroimaging studies suggests that cerebrovascular disease is associated with depressive disorders in the elderly, but the extent to which it contributes to the pathogenesis of late life depression is unclear. Objective: To investigate the relation between cerebral haemodynamics and depression in a population based study, using transcranial Doppler ultrasonography. Methods: Cerebral blood flow velocity and CO 2 induced vasomotor reactivity in the middle cerebral artery were measured in 2093 men and women who participated in the Rotterdam study. All subjects were screened for depressive symptoms using the Center of Epidemiological Studies Depression scale, and those with a score of 16 or over had a psychiatric work up. In a semistructured interview, diagnoses of depressive disorders according to the DSM-IV and subthreshold depressive disorder were established. Analyses of covariance controlled for age, sex, stroke, cognitive score, and cardiovascular risk factors were used to compare means of haemodynamic variables. Results: Subjects with depressive symptoms had reduced blood flow velocities (mean difference, −2.9 cm/s; 95% confidence interval (CI), −5.0 to −0.8; p = 0.008) and lower vasomotor reactivity (mean difference −0.5%/kPa; 95% CI, −1.0 to −0.05; p = 0.03). Blood flow velocity was reduced most in subjects suffering from a DSM-IV depressive disorder (mean difference, −4.9 cm/s; 95% CI, −8.5 to −1.4; p = 0.006). The overall reduction in vasomotor reactivity was accounted for by subjects with subthreshold depressive disorder. Conclusions: Depression in late life is associated with cerebral haemodynamic changes that can be assessed by transcranial Doppler ultrasonography. The observed reduction in cerebral blood flow velocity could be a result of reduced demand in more seriously depressed cases with a DSM-IV disorder, whereas reduced CO 2 induced cerebral vasomotor reactivity is a possible causal factor for subthreshold depressive disorder.

Objective: To investigate the time relation between dementia and major affective disorders (major depression and mania). Methods: Register linkage study of the Danish Hospital Register and the Danish Psychiatric Central Research Register, to establish study cohorts of patients with dementia and control groups (osteoarthritis or diabetes) on first discharge from hospital. Follow up of cohorts was for up to 21 years. Hazard of death was allowed for by the use of competing risks models. Results: Patients with dementia had an increased risk of being admitted to hospital for major depression or mania during the course of the illness. The incidence remained elevated throughout the rest of the patient's life. Conclusions: Patients with dementia have an increased risk of developing depression or mania. Proper treatment of affective disorders in patients with dementia is important in reducing suffering and costs.

Objective: to analyse 24 parkinsonian patients successfully treated by bilateral STN stimulation for the presence of behavioural disorders. Method: patients were evaluated retrospectively for adjustment disorders (social adjustment scale, SAS), psychiatric disorders (comparison of the results of psychiatric interview and the mini international neuropsychiatric inventory) and personality changes (IOWA scale of personality changes). Results: parkinsonian motor disability was improved by 69.5% and the levodopa equivalent daily dosage was reduced by 60.5%. Social adjustment (SAS) was considered good or excellent in nine patients, moderately (n=14), or severely (n=1) impaired in 15 patients. Psychiatric disorders consisted of amplification or decompensation of previously existing disorders that had sometimes passed unnoticed, such as depressive episodes (n=4), generalised anxiety (n=18), and behavioural disorders with drug dependence (n=2). Appearance of mild to moderate emotional hyperreactivity was reported in 15 patients. Personality traits (IOWA scale) were improved in eight patients, unchanged in seven, and aggravated in eight Conclusion: Improvement in parkinsonian motor disability induced by STN stimulation is not necessarily accompanied by improvement in psychic function and quality of life. Attention is drawn to the possible appearance of personality disorders and decompensation of previous psychiatric disorders in parkinsonian patients who are suitable candidates for neurosurgery. We suggest that a careful psychological and psychiatric interview be performed before surgery, and emphasise the need for psychological follow up to ensure the best possible outcome.