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Huntington's disease (HD) is an inherited neurodegenerative disease involving motor, cognitive, psychiatric, and behavioral impairments that eventually affect work-role functioning. There is limited research regarding predictors of workplace disability in HD. The authors examined predictors of work impairment and disability in a cross-sectional cohort of employed persons with symptomatic HD participating in the worldwide Enroll-HD study.The study sample (N=316) comprised individuals with manifest HD and a CAG repeat length range between 39 and 60 and were currently engaged in paid full- or part-time employment. Univariate and multivariate logistic regression analyses identified predictors and the effect of all predictors in a fully adjusted model.Of the sample, 20.3% reported missing work due to HD, 60.1% reported experiencing impairment while working due to HD, 79.1% reported having work-related activity impairment due to HD, and 60.8% reported impairment in overall work productivity due to HD. Individuals had 25% higher odds of missing work time if they had a higher level of functional impairment (odds ratio=0.76, 95% CI=0.64, 0.91) and had three times greater odds of missing work if they were current alcohol drinkers, compared with nondrinkers (odds ratio=2.86, 95% CI=1.62, 5.03). Individuals with lower self-perceived mental health were also 5% more likely to experience impairment at work due to HD. Motor impairment was not a strong predictor of workplace disability.These findings provide important new knowledge that can inform the development of strategies or targeted intervention trials to support persons with symptomatic HD to maintain their work roles.

Huntington disease (HD) is a neurodegenerative condition with prominent motor (including oculomotor), cognitive, and psychiatric effects. While neuropsychological deficits are present in HD, motor impairments may impact performance on neuropsychological measures, especially those requiring a speeded response, as has been demonstrated in multiple sclerosis and schizophrenia. The current study is the first to explore associations between oculomotor functions and neuropsychological performance in HD. Participants with impaired oculomotor functioning performed worse than those with normal oculomotor functioning on cognitive tasks requiring oculomotor involvement, particularly on psychomotor speed tasks, controlling for covariates. Consideration of oculomotor dysfunction on neuropsychological performance is critical, particularly for populations with motor deficits.

Background:The literature available on the format of the feedback session following assessment of memory impairment is minimal. This study explored how this information should be presented from the perspective of patients and their families.Methods:Thirty-two semi-structured interviews were conducted with memory clinic patients and their carer at the clinic visit that followed the feedback session, to ask: what they recalled, what they found helpful, and what they thought was the best way to disclose a diagnosis of dementia. A second interview was conducted with 14 patient/carer dyads at their next appointment.Results:Recall of information from the feedback session was variable. Most respondents (76% of patients; 66% of carers) thought that a direct approach was best when informing the patient of a dementia diagnosis, and that both written information and compassion demonstrated by the doctor were helpful. Opinions on whether all the information should be given at once or in stages were divided.Conclusions:The current format of the feedback session needs revision to improve recall. Patients and their families want a direct approach to be used by a supportive and professional doctor with an opportunity to ask questions. They want the support of a family member or friend when they are told of their diagnosis and they would like a written summary to refer to afterwards.

Associate-recognition has received little attention as a potential clinical tool for detecting early Alzheimer's disease (AD). As an important preliminary stage to investigating the paradigm's diagnostic utility, we designed and administered a verbal associate-recognition task to healthy elderly participants (n = 62) and compared their performance to that on traditional cued-recall PAL. In both test conditions, the stimulus list comprised of a mixture of highly imageable and less imageable word pairs. Overall, performance on the associate-recognition task was superior to that on the cued-recall analogue. This 'recognition advantage' was not attributable to the higher baseline or chance guessing rate in the associate-recognition condition, as the size of the recognition advantage varied across learning trials and stimulus imageability. In comparison to performance on the imageable stimuli, performance on the less imageable stimuli was poor in both associate-recognition and cued-recall conditions. Across the delay, performances were more likely to drop in the cued-recall condition than the associate-recognition condition. These results suggest that verbal associate-recognition may be clinically efficacious and better tolerated in elderly populations than traditional cued-recall paradigms. Although these results are encouraging, further research is required to examine the utility of associate-recognition in clinical populations, particularly early AD.

The primary impairment in early Alzheimer's disease (AD) is encoding/consolidation, resulting from medial temporal lobe (MTL) pathology. AD patients perform poorly on cued-recall paired associate learning (PAL) tasks, which assess the ability of the MTLs to encode relational memory. Since encoding and retrieval processes are confounded within performance indexes on cued-recall PAL, its specificity for AD is limited. Recognition paradigms tend to show good specificity for AD, and are well tolerated, but are typically less sensitive than recall tasks. Associate-recognition is a novel PAL task requiring a combination of recall and recognition processes. We administered a verbal associate-recognition test and cued-recall analogue to 22 early AD patients and 55 elderly controls to compare their ability to discriminate these groups. Both paradigms used eight arbitrarily related word pairs (e.g., pool-teeth) with varying degrees of imageability. Associate-recognition was equally effective as the cued-recall analogue in discriminating the groups, and logistic regression demonstrated classification rates by both tasks were equivalent. These preliminary findings provide support for the clinical value of this recognition tool. Conceptually it has potential for greater specificity in informing neuropsychological diagnosis of AD in clinical samples but this requires further empirical support. (JINS, 2008,14, 591–600.)

Research in preclinical mutation carriers for Huntington's disease (HD) aims to find measures sensitive to preclinical decline. This study investigated attentional abilities in mutation carriers and noncarriers. Mutation carriers demonstrated a normal "attentional blink" during rapid serial visual presentation, normal covert visual orienting, and normal directing of attention to tactile stimuli. However, they were more likely than noncarriers to make anticipatory responses before target presentation. Additionally, those closer to estimated onset of HD demonstrated larger "inhibition of return" effects. The findings suggest potential changes in cognitive inhibition of unwanted responses, and in automatic inhibition of visual orienting, in preclinical HD.

One consistent functional imaging finding from patients with major depression has been abnormality of the anterior cingulate cortex (ACC). Hypoperfusion has been most commonly reported, but some studies suggest relative hyperperfusion is associated with response to somatic treatments. Despite these indications of the possible importance of the ACC in depression there have been relatively few cognitive studies ACC function in patients with major depression. The present study employed a series of reaction time (RT) tasks involving selection with melancholic and nonmelancholic depressed patients, as well as age-matched controls. Fifteen patients with unipolar major depression (7 melancholic, 8 nonmelancholic) and 8 healthy age-matched controls performed a series of response selection tasks (choice RT, spatial Stroop, spatial stimulus-response compatibility (SRC), and a combined Stroop + SRC condition). Reaction time and error data were collected. Melancholic patients were significantly slower than controls on all tasks but were slower than nonmelancholic patients only on the Stroop and Stroop + SRC conditions. Nonmelancholic patients did not differ from the control group on any task. The Stroop task seems crucial in differentiating the two depressive groups, they did not differ on the choice RT or SRC tasks. This may reflect differential task demands, the SRC involved symbolic manipulation that might engage the dorsal ACC and dorsolateral prefrontal cortex (DLPFC) to a greater extent than the, primarily inhibitory, Stroop task which may engage the ventral ACC and orbitofrontal cortex (OFC). This might suggest the melancholic group showed a greater ventral ACC-OFC deficit than the nonmelancholic group, while both groups showed similar dorsal ACC-DLPFC deficit.

BACKGROUND: Atypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance, but have similar efficacy to conventional antipsychotics. Trials in the elderly have been either retrospective, small, of short duration or of a single-arm design. AIMS: To demonstrate the effects upon motor side-effects, efficacy, safety and quality of life (QOL) of switching elderly patients with schizophrenia from conventional antipsychotics to olanzapine or risperidone. METHODS: Elderly patients with schizophrenia were randomly allocated to olanzapine or risperidone and followed through an open-label crossover period. Between and within group intention to treat analyses were conducted. RESULTS: 66 patients were randomised (mean age 69.6 [SD +/- 6.2]). Four (11.8%) patients on olanzapine and 8 (26.7%) patients on risperidone failed to complete the crossover because of treatment failure [Odds Ratio (OR) = 2.73[0.73-10.2] p = 0.14]. The mean doses upon completion of switching in each arm were 9.9 mg (SD = 4.2) and 1.7 mg (SD = 1.2) for olanzapine and risperidone respectively. In both arms there was improvement in Parkinsonism, though only olanzapine was associated with a reduction in dyskinetic symptoms. The Brief Psychiatric Rating Scale, Scale for the assessment of Negative Symptoms and Montgomery and Asberg Depression Rating Scale scores all improved through the crossover period in both arms with no between group differences. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the World Health Organisation-Quality Of Life [Brief] (WHO-QOL-BREF) scale ( p = 0.02). Patients in the olanzapine arm also demonstrated improvement from baseline in the WHO-QOL-BREF physical, psychological and health satisfaction domains, but risperidone had no effect on any Quality of Life (QOL) measure. CONCLUSIONS: After switching from a conventional antipsychotic, olanzapine and risperidone were associated with improvement in core symptoms of schizophrenia and motor side effects. Subjects switched to olanzapine were more likely to complete the switching process and show an improvement in psychological QOL. Copyright 2003 John Wiley & Sons, Ltd

Mental rotation (MR) performance may be used as an index of mental slowing or bradyphrenia, and may reflect, in particular, speed of motor preparation. MR was employed with a sample of both melancholic (na 8) and non-melancholic (na 9) unipolar depressed patients and healthy controls (na 10) to determine if motor slowing associated with depression might be reflected in slowed motor preparation (as reflected in slope of the MR function) independent of actual motor slowing (overall response time). Both melancholic and non-melancholic patients showed a generalised slowing relative to controls, perhaps reflecting bradykinesia and akinesia. This effect was significantly greater in the melancholic group than in the non-melancholic group. Relative to both the controls and the non-melancholic groups, the melancholic patients showed a progressive slowing with increasing angle of orientation indicating a specific slowing of MR. This deficit suggests a role of slowed motor planning in the psychomotor retardation of patients with melancholic depression.

Movement-related potentials (MRPs) reflect increasing cortical activity related to the preparation and execution of voluntary movement. Execution and preparatory components may be separated by comparing MRPs recorded from actual and imagined movement. Imagined movement initiates preparatory processes, but not motor execution activity. MRPs are maximal over the supplementary motor area (SMA), an area of the cortex involved in the planning and preparation of movement. The SMA receives input from the basal ganglia, which are affected in Huntington's disease (HD), a hyperkinetic movement disorder. In order to further elucidate the effects of the disorder upon the cortical activity relating to movement, MRPs were recorded from ten HD patients, and ten age-matched controls, whilst they performed and imagined performing a sequential button-pressing task. HD patients produced MRPs of significantly reduced size both for performed and imagined movement. The component relating to movement execution was obtained by subtracting the MRP for imagined movement from the MRP for performed movement, and was found to be normal in HD. The movement preparation component was found by subtracting the MRP found for a control condition of watching the visual cues from the MRP for imagined movement. This preparation component in HD was reduced in early slope, peak amplitude, and post-peak slope. This study therefore reported abnormal MRPs in HD, particularly in terms of the components relating to movement preparation, and this finding may further explain the movement deficits reported in the disease.

The ability of Huntington's disease patients to co-ordinate their two hands with and without external cueing was investigated. Twelve Huntington's disease patients and sex- and age-matched controls performed a bimanual cranking task at two speeds (0.5 Hz, 1.5 Hz) and phase relationships (in-phase, anti-phase), with and without an external metronome cue. Data were sampled at 200 Hz, and raw displacement data for each hand, mean and standard deviation measures of the relative positions of the two hands and their velocities were then calculated. All participants could perform the in-phase movement, at both speeds; however. the Huntington's disease patients were more variable and less accurate than the control participants, particularly at the fast speed. While controls could perform the anti-phase movement, in which rotation of the cranks differed by 180 degrees at both speeds, Huntington's disease patients were unable to do so at either speed, reverting to the in-phase movement at the slow speed. An external metronome cue did not improve the performance of the Huntington's disease patients, which differentiated this group from patients suffering from Parkinson's disease. The Huntington's disease patients' inability to perform the anti-phase movement may be due to damage to the basal ganglia and its output regions.

Clinical observation points to similarities between psychomotor retardation in major depression and bradykinesia in Parkinson's disease (PD). While common elements of neuropathology have been proposed to account for this, experimental investigations of this possible link have been few and inconclusive. The present study attempts to determine whether patients with depression display the characteristically Parkinsonian reliance on external cues; and if so, whether this is common to both melancholic and non-melancholic patients. Twenty three patients with unipolar major depression (11 melancholic and 12 non-melancholic) and 24 age-matched healthy controls performed a serial choice reaction time task known to be sensitive to Parkinsonian movement deficits. The melancholic patients showed a Parkinsonian pattern of impairment on the task, exhibiting a particular difficulty when initiating movements in the absence of external cues. This was largely alleviated when a moderate amount of external cueing was provided. At a high level of advance information, melancholic patients were again slow relative to controls. A base-line measure of bradykinesia and a derived measure of dependence upon external cues both correlated significantly with CORE (measure of psychomotor disturbance) ratings. The non-melancholic patients did not show any measurable motor impairment. This cue-dependent deficit may be due to an underlying basal ganglia dysfunction similar to that involved in PD, i.e. a failure of internal cueing. Difficulty with a high level of external cueing might reflect bradyphrenia or a prefrontal motor deficit of ability to plan multiple upcoming movements simultaneously. The results suggest that depression subtypes involve differing patterns of fronto-striatal impairment.

As part of a larger study, the Lehman Quality of Life Interview (QOLI) was conducted a total of 85 times with 55 clients with serious mental illness. Results revealed widespread adverse objective circumstances (unemployment, poverty and social isolation) despite which most clients rated their satisfaction levels about average (about equally satisfied and dissatisfied). As expected, subjective quality of life indicators were generally better predictors of global well-being (GWB) (itself based on subjective ratings) than were objective indicators. Correlations between objective and subjective indicators were very low and insignificant. Moderate relationships were found between GWB and levels of personal functioning, and changes in levels of personal functioning, as rated by mental health workers. Retests showed that subjective quality of life was relatively stable over intervals of several months. The findings suggest that leisure and social relations would be suitable areas for interventions that might improve clients' quality of life.

Background Previous work suggests that temporal lobe magnetic resonance imaging (MRI) can distinguish those with dementia of the Alzheimer type (DAT) from healthy age-matched controls. However, its specificity with regard to conditions such as vascular dementia, depression and other disorders associated with cognitive impairment has not been determined. Methods We studied 222 subjects using T1 weighted MRI with 5.1 mm coronal slices throughout the temporal lobe. Subjects included: healthy controls (N = 40); DSM-III-R major depression (N = 61); NINCDS/ADRDA DAT (N = 77) and OTHER (N = 44, comprising subjects with vascular dementia, Huntington's disease, schizophrenia, alcohol related cognitive impairment and a group of 'memory complainers'). Hippocampus, amygdala, entorhinal cortex, parahippocampal gyrus and cerebral cortex were rated visually on a 0-3 scale by two experienced neuroradiologists blind to clinical diagnosis. Results Ratings of temporal lobe atrophy provided good separation between those with AD and all other groups. For example, anterior hippocampal atrophy had a sensitivity of 83% for detecting DAT, a specificity of 80% for controls, 87% for depressed subjects and 89% for OTHER. Other regions were less sensitive, but more specific for the diagnosis of DAT. In particular parahippocampal gyrus and entorhinal cortex had high specificity (97% for depressed subjects and 98% for OTHER). Because of an age-related increase in atrophy, sensitivity was highest for those over the age of 75, while specificity was highest for younger subjects. Significant correlations were observed between atrophy ratings of hippocampus, amygdala, entorhinal cortex and parahippocampal gyrus and CAMCOG memory score and length of history. Conclusions Temporal lobe MRI may have an important role in assisting with the clinical diagnosis of DAT, particularly its differentiation from depression and other disorders that may cause diagnostic difficulties in clinical practice.

Adoptive immunity transfer has been reported to be effective in clearing chronic hepatitis B virus (HBV) infection. Two hundred twenty-six patients who received allogeneic bone marrow transplantation (BMT) between May 1990 and September 1995 were screened for hepatitis B markers. Twenty-one patients were hepatitis B surface antigen (HBsAg) positive before BMT. The median follow-up period was 20 months (range, 2-59 months). Two of these patients had sustained clearance of HBV infection after transplantation. Both patients were hepatitis B e antigen (HBeAg)-negative, hepatitis B e antibody (anti-HBe)-positive, and serum HBV DNA-negative (by dot-blot hybridization) before BMT. Both had a flare in the serum alanine transaminase (ALT) level around the time of HBsAg clearance. Sustained clearance of HBsAg was observed in 2 of the 5 patients who received hepatitis B surface antibody (anti-HBs)-positive marrow but in none of the 16 patients who received anti-HBs-negative marrow (P < .05). One additional patient who received anti-HBs-positive marrow had transient HBsAg seroconversion. Among the 18 patients who remained persistently HBsAg-positive after BMT, 3 had HBeAg seroconversion and 3 had reversion to HBeAg positivity. In this study, we found a significant association between clearance of HBV infection and anti-HBs-positive bone marrow donors. Adoptive immunity transfer is effective in clearing HBV from patients with chronic HBV infection.

This study aimed to quantify the efficiency and smoothness of voluntary movement in Huntington's disease (HD) by the use of a graphics tablet that permits analysis of movements profiles. In particular, we aimed to ascertain whether a concurrent task (digit span) would affect the kinematics of goal-directed movements. Twelve patients with HD and their matched controls performed 12 vertical zig-zag movements, with both left and right hands (with and without the concurrent task), to large or small circular targets over long or short extents. The concurrent task was associated with shorter movement times and reduced right-hand superiority. Patients with HD were overall slower, especially, with long strokes, and had similar peak velocities for both small and large targets, so that controls could better accommodate differences in target size. Patients with HD spent more time decelerating, especially with small targets, whereas controls allocated more nearly equal proportions of time to the acceleration and deceleration phases of movement, especially with large targets. Short strokes were generally less force inefficient than were long strokes, especially so for either hand in either group in the absence of the concurrent task, and for the right hand is its presence. With the concurrent task, however, the left hand's behavior changed differentially for the two groups; for patients with HD, it became more force efficient with short strokes and even less efficient with long strokes, whereas for controls, it became more efficient with long strokes. Controls may be able to divert attention away from the inferior left hand, increasing its automaticity, whereas patients with HD, because of disease, may be forced to engage even further online visual control under the demands of a concurrent task. Patients with HD may perhaps become increasingly reliant on terminal visual guidance, which indicates an impairment in constructing and refining an internal representation of the movement necessary for its effective execution. Basal ganglia dysfunction may impair the ability to use internally generated cues to guide movement.

Hepatitis B reactivation following chemotherapy withdrawal may result in hepatitis, hepatic failure and death. We studied the clinical outcome and the causes of hepatic events of hepatitis B surface antigen positive recipients undergoing bone marrow transplantation. Twenty-four hepatitis B surface antigen patients were matched with 24 hepatitis B surface antigen negative patients for age, sex, CMV positive serology, underlying hematological disease and type of bone marrow transplantation. Post-BMT, there were 18 patients in the hepatitis B surface antigen positive group and four patients in the hepatitis B surface antigen negative group who suffered from hepatitis (P < 0.05). Thirteen of the 18 hepatitis were related to HBV reactivation in the hepatitis B surface antigen positive group and none of the four hepatitis in the hepatitis B surface antigen negative group (P = 0.01). The hepatitis B surface antigen positive group also had an increased incidence of acute graft-versus-host disease of liver (6 vs 1, P = 0.03). However, there was no significant increase in the incidence of veno-occlusive disease (10 vs 7, P = 0.40) and persistent hepatitis (3 vs 0, P = 0.07) in the hepatitis B surface antigen positive group. Using the log-rank test, there was no significant difference in survival between the hepatitis B surface antigen positive and negative recipients.

Aims: This study examines elements of genetic discrimination among an at-risk, clinically undiagnosed Huntington's disease (HD) population. Methods: Sixty at-risk individuals, either positive or negative for the HD genetic mutation, completed a survey regarding their experiences of genetic discrimination, adverse and unfair treatment, and knowledge about existing laws and policies surrounding genetic discrimination. Results: Sixty eight percent of participants reported feeling “Great benefit” from knowing their genetic test results. Reported benefits of knowledge included planning for the future, making decisions, and many individuals found meaning in active participation in the HD community and in advocating for themselves or families at risk for HD. Many individuals found personal meaning and a sense of community from knowledge of this information and from the ability to participate in research. Despite these positive feelings toward gene testing, results demonstrated that 33% of participants perceived experiences of genetic discrimination, which occurred repeatedly and caused great self-reported distress. Significantly, more gene-positive respondents reported experiencing incidents of genetic discrimination, compared to gene-negative respondents. At least 58 separate incidents of discrimination were reported, the number of incidents ranged from 1 to 10, with 45% of individuals (9/20 respondents) indicating more than one event. Of the most significant events of discrimination, 58% were related to insurance, 21% to employment, 16% to transactions of daily life, and 5% to relationships. Conclusion: Results contribute toward validation of empirical data regarding genetic discrimination.

Neuropsychological performance in 20 chronic schizophrenic patients was contrasted to 25 Parkinson's disease, 12 Huntington's disease patients and 26 normal controls on measures shown to be sensitive to subcortical dysfunction. Some overlap was observed in the performance of the schizophrenic and basal ganglia groups on tasks of executive and mnestic function, but the general pattern indicated significant differences in performance. Notably, in contrast to the two basal ganglia groups, there was no evidence of slowed thinking, or impaired motor function in schizophrenia, which are considered hallmarks of subcortical grey matter disease. An association was observed between poor performance on the tests of executive function and the severity of negative symptoms. Our findings suggest that schizophrenia is not associated with primary subcortical impairment, but is more likely to reflect frontotemporal dysfunction. We consider that the similarities between this disorder and subcortical degenerative syndromes may be due to a difficulty in generating action in schizophrenia, perhaps arising from dorsolateral prefrontal disconnection.

Summary: To identify the focus of impairment in the performance of sequential movements in Huntington’s disease (HD) patients, the extent of their reliance on external advance information was examined. Twelve patients with HD and their age-matched controls performed a series of button-presses at sequential choice points along a response board. A sequential pathway was designated, and with each successive button press, advance visual information was systematically reduced to various extents in advance of each move. HD patients, like previously studied parkinsonian patients, were particularly disadvantaged with high levels of reduction in advance information, and as a consequence, both their initiation and execution of movements progressively slowed with each successive element in the response sequence. The pattern of results was not affected whether or not patients were taking neuroleptic medication, nor did performance on a variety of cognitive measures correlate with motor performance. Control subjects’ performance, on the other hand, remained constant in terms of both initiation and execution with each of the three levels of reduction in advance information. We conclude that HD patients, like parkinsonian patients, who also suffer from a basal ganglia (BG) disorder, require external visual cues to sequence motor programs effectively. Our findings suggest that with HD there may be abnormalities in a central mechanism that controls switching between movement segments within an overall motor plan. The BG, which provide internal cues necessary for component sequencing, may be disrupted, thereby impairing the ability to use such internally generated cues to guide movement. Key Words: Huntington’s diseaseAdvance information-Internal cues-Basal ganglia.

Thirty-nine Chinese patients presenting as essential thrombocythemia (ET) were analyzed retrospectively. The median age at presentation was 69 years and the M:F ratio was 1.35:1. At diagnosis, 33 cases (84%) were asymptomatic and the diagnosis was made incidentally, while 3 cases (8%) presented with small vessel, and 2 cases (5%) with large vessel, thrombosis. One patient (3%) presented with minor bleeding. The platelet count ranged from 0.9-34 x 10(12)/l. Of 12 karyotypes done, 2 cases were abnormal, both showing the Philadelphia (Ph) chromosome. First-line therapy was radiophosphorus (32P) in 3 cases, melphalan in 20 cases, and hydroxyurea in 12 cases; 4 cases did not receive specific therapy. During the follow-up (mean = 4 years), no thrombotic or bleeding episodes were observed. One patient with the Ph chromosome underwent blastic transformation. These results indicate that bleeding and thrombosis occur significantly less in Chinese patients than in Western patients. The Ph chromosome appears to be a bad prognostic indicator. Because of the very low incidence of complications and good prognosis, the authors believe that cytoreductive therapy is best achieved by the use of hydroxyurea instead of alkylating agents or radiophorphours, as the latter agents are potentially leukemogenic.

Fifty patients with previously untreated acute myeloid leukemia were treated with an induction regimen consisting of cytosine arabinoside 100 mg/m2 per day by 18 h i.v. infusion for 7 days, daunorubicin 50 mg/m2 per day by i.v. bolus injection for 3 days and etoposide 75 mg/m2 per day by 1 h i.v. infusion for 7 days. Thirty seven of them (74%) went into complete remission (CR) and they all then received two consecutive courses of consolidation chemotherapy consisting of cytosine arabinoside 500 mg/m2 per day by 1 h i.v. infusion every 12 h for 4 days (total eight doses) and mitoxantrone 12 mg/m2 daily by 30 min i.v. infusion for 3 days. They were followed by maintenance chemotherapy with cytosine arabinoside and thioguanine 2 monthly. With a median follow up time of 24 months, 20 of the 37 complete responders had relapsed (54%). The disease-free survival (DFS) of 37 CR patients and the overall survival of all patients at 24 months were 37 and 44%, respectively. Age of patients and number of courses of induction chemotherapy to achieve CR were significant factors predicting DFS. Myelosuppression was the major toxic side effects. Ten patients had prolonged marrow suppression following consolidation chemotherapy. In conclusion, despite the significant myelosuppression observed, overall improvement in treatment outcome was not demonstrable with the use of this intensive consolidation therapy.

Tourette's syndrome is a chronic neurological disorder manifested by involuntary motor tics and vocalisations. Because the basal ganglia have been implicated in the pathology underlying Tourette's syndrome, the present two procedures, both involving sequential movements, sought to determine the extent to which patients with Tourette's syndrome were reliant on, and could utilise different levels of advance information. Patients with Tourette's syndrome were found to be more reliant than controls on external visual cues to execute rather than to initiate a motor programme. When there was a high level of reduction in advance information--that is, a visual pathway to be followed was extinguished well in advance of each successive movement--executions progressively slowed as the sequence was traversed. Similarly, if no advance information was provided before each move, movement execution was slower than that of controls. The movement initiation times of patients with Tourette's syndrome were, however, similar to those of controls, as were their movement execution times when advance visual information was available. It seems that patients with Tourette's syndrome, like parkinsonian patients who are known to have a basal ganglia disorder, require external sensory cues to sequence a motor programme effectively. The present study found evidence consistent with the hypothesis that patients with Tourette's syndrome, like patients with Parkinson's disease, may be dysfunctional in internal switching mechanisms. Alternatively, with limited visual guidance, patients with Tourette's syndrome, regardless of medication or depression state, may require more time to plan and programme each next submovement, and under such conditions may require external visual cues to direct attention effectively to given targets. Although the underlying pathogenesis is still speculative, it is concluded that there is much to support the notion that Tourette's syndrome may stem from abnormalities of the major pathways between the basal ganglia and the frontal lobes.

Summary Tourette's syndrome and Huntington's disease have long been clinically associated with attentional deficits. In this study, we aimed to determine the nature and quantify the extent of such deficits. A technique was devised to ascertain the efficiency with which Tourette's syndrome and Huntington's disease patients could shift and direct attention away from naturally expected stimulus—response (S-R) linkages. This was done by varying the relationships formed between stimulus and response location. Attentional efficiency was indicated by relative speed of responding to relevant (congruent) and irrelevant (incongruent) stimuli, in a paradigm developed from the Simon effect. There were five conditions progressively increasing in complexity. The stimuli consisted of left and right pointing arrows and, in some cases, various conditionality manipulations were also employed, such that in the presence of a certain symbol (i.e. ‘ x ’) the nature of the response had to be reversed, whereas in the presence of an alternative symbol (i.e. ‘=’), the response was compatible with the direction of the arrow. As predicted, Tourette's syndrome and Huntington's disease patients, regardless of medication or depression status and unlike controls, were particularly disadvantaged in responding to various conflicting S-R configurations. Tourette's syndrome and Huntington's disease patients may experience difficulties in making attentional shifts, or in inhibiting inappropriate responses; they may also be more susceptible (than controls) to the conflict that can arise when the spatial code formed for the stimulus is irrelevant for selecting the appropriate response. We conclude that our findings support the notion that cognitive deficits in Tourette's syndrome and Huntington's disease may stem from abnormalities of the major pathways interconnecting the basal ganglia and the frontal lobes.

The gastrointestinal tract is a common primary extranodal site for non-Hodgkin's lymphoma. There is however no uniform consensus on its pathological classification, clinical staging system and management. This paper reports the experience in the management of 425 Chinese patients with primary gastrointestinal lymphoma in Hong Kong from January 1975 to June 1993. There were 230 (54 per cent) males and 195 (46 per cent) females. Their median age was 53 years. The primary sites were: the esophagus in three (1 per cent), stomach in 238 (56 per cent), small intestine in 131 (31 per cent) and large intestine in 53 (12 per cent). According to the Working Formulation, there were 20 (4.7 per cent) small lymphocytic, 10 (2.4 per cent) follicular small cleaved cell, 15 (3.5 per cent) follicular mixed, five (1.2 per cent) follicular large cell, 40 (9.4 per cent) diffuse small cleaved cell, 50 (12 per cent) diffuse mixed, 181 (43 per cent) diffuse large cell, 30 (7.1 per cent) immunoblastic, five (1.2 per cent) lymphoblastic, 10 (2.4 per cent) diffuse small non-cleaved cell and 50 (14 per cent) unclassifiable lymphoma. Immunophenotyping was performed in 199 (47 per cent) patients: 90 per cent B-cell, 7 per cent T-cell and 3 per cent uncertain. According to a Manchester system, 81 (19 per cent) patients had stage I disease, 44 (10 per cent) stage II, 85 (20 per cent) stage III and 215 (51 per cent) stage IV. B symptoms were present in 275 (65 per cent) patients and bulky disease in 104 (25 per cent). Surgery followed by chemotherapy was the mainstay of treatment. Of the 408 patients treated, 63 per cent had a complete remission with relapse rate of 42 per cent. For those with complete remission, 47 per cent were free from disease at 5 years. The overall median survival of all patients was 45 per cent at 5 years. Multivariate analysis revealed that significant independent prognostic factors predicting better survival were young age of < 60 years, low grade histology, stage I and II disease and absence of bulky tumour. For gastric lymphoma, aggressive surgery did not significantly improve their outcome. Chemotherapy appears to play an important role in the management of gastrointestinal lymphoma. Better classification of the primary gastrointestinal lymphoma and more refined stratification of the patients according to the prognostic variables may allow individualization of treatment. Prospective randomized studies are essential to define the relative roles of surgery, chemotherapy and radiotherapy.

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction and depression have both been shown to occur in Huntington's disease (HD) gene carriers prior to diagnosis (pre-HD) and in diagnosed HD patients. However, the relationship between HPA axis dysfunction and the severity of depressive symptomatology in pre-HD and early-HD has not been systematically examined, despite morning hypercortisolism being a characteristic feature of some subtypes of idiopathic depression. The aim of this study was to investigate whether HPA axis function is related to levels of depression in pre-HD and early-HD. To assess HPA axis function we obtained salivary cortisol concentrations from 20 controls, 20 pre-HD, and 17 early-HD participants at four time points over a 24h period. Depression symptoms were assessed using the Inventory of Depressive Symptomatology - Self-Report. Of the participants who were found not to be depressed, the early-HD group had significantly lower morning cortisol levels relative to pre-HD and controls. In contrast, the early-HD group with at least mild or greater levels of depression symptoms had a comparable cortisol concentration to pre-HD and controls. The results suggest that early-HD may be associated with hypocortisolism. However when depressed, a hyperactive HPA axis response may still be induced in early-HD and lead to cortisol levels that are similar to pre-HD and controls. Our study reveals that cortisol levels in HD may be modified by the presence or absence of depressive symptomatology. Depression may be an important factor for understanding how the HPA axis is affected in HD, particularly in the morning.

Patients with Huntington's disease exhibit poorer-quality handwriting, sometimes clinically exhibiting macrographia, an increase in the size of handwriting. To characterize deficits in handwriting of patients with Huntington's disease, we compared the writing of 12 young, 12 age-matched controls, and 12 patients with Huntington's disease. Subjects were asked to write the letter "l" four times, at a constant length, on a graphics tablet that sampled pen position at 200 Hz. Huntington's disease causes chorea (involuntary movement), akinesia (difficulty in initiating voluntary movement), and bradykinesia (slowness and difficulty in maintaining voluntary movement). To distinguish changes in handwriting quality due to involuntary movement from impairments of voluntary movement, handwriting samples with obvious choreic movements were analyzed separately from other handwriting samples. Several measures of quality of handwriting were considered, based on: the regularity and consistency of handwriting, the efficiency of movement trajectories, and the proportions of movement occurring at specific frequencies. Results suggested that Huntington's disease increases variability of movement parameters, and causes problems in producing smooth movements. Choreic movement was best characterized by the number of zero crossings in the velocity function relative to the prescribed number of writing strokes. We hypothesize that macrographia in Huntington's disease occurs when chorea predominates over bradykinesia. Comparisons were made between the handwriting of patients with Huntington's and Parkinson's diseases.

One hundred and forty-one consecutive patients above and 231 below the age of 60 years with previously untreated intermediate or high grade non-Hodgkin's lymphoma were included in this study. Patients above the age of 60 years were treated with the COPP chemotherapy regimen. The younger patients, at or below the age of 60, received a doxorubicin-containing regimen (119 had CHOP, 65 had BACOP and 47 had m-BACOD). For stage I patients, the clinical results were similar but for stage II, III or IV disease, those receiving COPP had significantly worse CR rate and survival than those who had a doxorubicin-containing regimen. Multivariate analysis on patients receiving the COPP chemotherapy revealed that the independent prognostic variables significantly determining CR rate and survival included clinical stage (p = 0.04) and serum lactate dehydrogenase level (p = 0.001). Myelosuppression was the major toxicity following COPP chemotherapy in this group of patients. There were 10 (7 per cent) treatment-related deaths. Compared to the reported results using doxorubicin-containing regimens to treat elderly patients with aggressive NHL in the literature, the more aggressive treatment does not appear to improve significantly the clinical outcome of this group of patients and seems to produce treatment results very much similar to COPP. However, accurate comparison is difficult because of the variation in the patient characteristics. Further prospective controlled randomized trials will be necessary to determine the optimal therapy for these patients.

Victorian Aboriginal people, most of whom live an urban lifestyle, form a distinct cultural group within the wider Victorian community. This paper describes a unique psychosocial study of urban Aboriginal adults attending a general practitioner at the Victorian Aboriginal Health Service in Fitzroy. The frequency and nature of psychiatric disorders among survey respondents is reported, together with a discussion of the association between this morbidity and certain sociodemographic variables.

Recent research has shown that Huntington's disease (HD) causes problems in the initiation and execution of movement (akinesia, bradykinesia): information which is useful in documenting the functional progression of the disease. The present experiment used a sequential movement task to characterize such impairments. Eighteen patients diagnosed as suffering from HD, and a similar number of matched At-Risk (AR) and Normal control subjects, performed sequential button pressing tasks, under varying amounts of visual advance information. Specific dimensions of motor control were examined (hand, direction). Movement initiation and in particular movement duration were useful indicators of the functional progression of the disease, and also detected anomalies of performance in some AR individuals. Impaired motor programming was indicated by patients' difficulty in initiating movements in the absence of external visual cues, and their problems in utilizing advance information to control movement. Patients had specific deficits in initiating movements with the nonpreferred hand, and directional movement asymmetries were accentuated. The results suggest that HD causes difficulties at three discrete levels: in utilizing advance information, in the initiation and in the spatial representation of movement.

Maintenance of motor set in patients with unipolar major depression was examined. Twelve melancholic and 12 non-melancholic depressed patients and 24 age matched controls performed a serial choice reaction time task while external cues aiding maintenance of a motor set were systematically removed. Melancholic patients were significantly slower than controls with no reduction in external cues and with a moderate reduction in external cues. At a high level of reduction in external cues, seven of 12 melancholic patients (but only three of 12 non-melancholic patients and controls) were unable to complete the task; suggesting a greater reliance on external cues, perhaps implicating a failure of motor planning ability in melancholic patients. This, in turn, may point to a prefrontal (premotor) deficit in melancholic depression, with possible commonalities with Parkinson's disease.

A total of 176 patients with gastrointestinal lymphomas were reviewed. According to a modified staging classification, 51 of them had stage I/II disease and the remaining 125 had stage III/IV disease. In most cases (68%), the histology was intermediate-grade according to the NIH working formulation, and the B-cell immunophenotype was involved in 89% of the 45 cases with a known immunophenotype. The primary site was the stomach in 56% of cases and the bowel in 44%. A significantly higher proportion (P = 0.001) of those with bowel lymphomas had stage III/IV disease (88% vs 57%). The primary gastrointestinal lesion was resected in 122 patients, including all 51 cases of stage I/II disease. In all, 8 stage I/II patients were given radiotherapy alone following surgery and the other 43 underwent chemotherapy; of the latter, 19 received additional radiotherapy following chemotherapy. Chemotherapy was also given to 112 stage III/IV patients, 42 of whom underwent additional radiotherapy. Factors associated with a poorer prognosis included advanced disease, bowel lymphoma and advanced age. Although the complete response (CR) rate according to disease stage was similar, stage I/II patients receiving chemotherapy showed a significantly lower relapse rate, better disease-free survival following CR and improved survival as compared with those receiving radiotherapy alone. However, additional radiotherapy following chemotherapy did not further improve the clinical outcome.

The aim of this study was to determine the effect of immunophenotype on the clinical characteristics and prognosis of 144 adult Chinese patients with non-Hodgkin's lymphomas. Those entities with well-recognised immunophenotype and clinical characteristics were excluded. Significantly more patients with T-cell lymphomas had B symptoms (52 vs. 30%, p = 0.05) and fewer had bulky disease (7 vs. 25%, p = 0.04). Extranodal involvements of liver, spleen, marrow, nasal region and skin were significantly more common in T-cell lymphomas. On the other hand, gastro-intestinal involvement was more commonly seen in B-cell tumours. Induction chemotherapy of comparable intensity was used in treating these patients. The immunophenotype did not appear to affect significantly their prognosis.

Summary The authors report the clinical, pathological and immunological features of a case of T-lymphoblastic lymphoma presenting with protein-losing enteropathy. There was extensive multifocal involvement of the duodenum, jejunum and ileum. The mediastinum was not enlarged; the peripheral blood picture and bilateral bone marrow trephine biopsies were unremarkable. The tumor cells were positive for terminal deoxynucleotide transferase, CD3, CD2, CD7 and CD10; they were negative for CD1, CD5, CD4, CD8 and HLA-DR. The immunophenotype was that of an immature thymic T-cell. Monocytic and B-cell markers were negative. Despite initial dose reduction in chemotherapy, the patient still developed massive intestinal hemorrhage and succumbed 2 wks after treatment. Postmortem examination confirmed absence of thymic involvement. The overall picture strongly suggests a primary intestinal origin of this T-lymphoblastic lymphoma which contradicts the conventional wisdom that T-lymphoblastic lymphoma arises in the thymus from primitive cortical lymphocytes before rapidly disseminating.

Seventeen patients with non-Hodgkin's lymphoma involving the orbit were studied. There were 12 males and 5 females and their median age was 53 years. Three cases were classified as stage I, two as stage II and 12 as stage IV. The histology was small lymphocytic type in 4 of the 5 stage I and II cases, and immunophenotyping, confirming their B-cell origin, was performed in two of these cases. All stage I and II patients responded favourably to local radiotherapy alone. The 12 stage IV patients had a marked male predominance and more commonly an intermediate grade histology and T-immunophenotype. Several of the orbital lesions seemed to represent extension of nasal lymphomas. The stage IV patients had a poorer survival than the stage I and II patients but the difference was not statistically significant, probably due to the small number of patients.

During a 14-year period, 122 of 840 (14.5) Hong Kong patients with non-Hodgkin's lymphomas were diagnosed to have low-grade lymphomas according to the Working Formulation. Only 28 (23%) of them had stage I and II disease and local radiotherapy appeared to be curative in some of them. Although remissions were achieved with chemotherapy in a majority of the stage III and IV patients, a pattern of continuous relapses was noted in their disease-free survival curve. Multivariate analysis revealed that clinical stage and presence of B symptoms were significant independent prognostic factors.

The pattern of malignant lymphomas in the Hong Kong Chinese population is characterized by a low incidence of Hodgkin's disease and follicular lymphomas. The authors studied the immunoglobulin (Ig), T-cell receptor (TCR), and bcl-2 gene rearrangement in 62 cases of malignant lymphoma in this population by Southern blot hybridization. Two cases of Hodgkin's disease showed no rearrangement of the Ig and TCR genes. All 42 cases of B-cell lymphoma had Ig heavy chain (JH) rearrangement with or without additional rearrangement of the light chains (C kappa and C lambda). One case of diffuse B-cell lymphoma had additional T-cell receptor beta-chain (C beta) rearrangement. Sixteen of 18 cases of T-cell lymphoma had C beta rearrangement, and one case of T-lymphoblastic lymphoma had additional JH rearrangement. Two of eight (25%) cases of follicular lymphoma but only one of the 34 (2.9%) cases of diffuse B-cell lymphoma had bcl-2 rearrangement that was detected by pFL-1 probe. None of the 62 cases showed bcl-2 rearrangement using the pFL-2 probe. In conclusion, the Ig and TCR gene rearrangement pattern of the lymphomas found in Hong Kong correlates well with the T-cell and B-cell lineage, which is similar to reports in the white population. However, the incidence of bcl-2 gene rearrangement in follicular B-cell lymphoma is lower than that reported in the US but comparable with that in Japan.

This paper reviewed the clinical characteristics and treatment outcome of 484 lymphoma patients with known hepatitis B status. Comparisons were made between the hepatitis B surface antigen positive and negative patients. Also, the effect of treatment for lymphomas, including cytotoxic chemotherapy, in the hepatitis B antigen positive patients were analysed. The hepatitis B status was determined in 484 Chinese lymphoma patients at the time of initial diagnosis. Hepatic complications occurring during therapy for lymphomas were analysed. Although our lymphoma patients had a similar prevalence of hepatitis B markers of 42 per cent, they had a strikingly higher positive rate of 22 per cent for hepatitis B surface antigen and a relatively lower positive rate of 20 per cent for antibody, as compared to the respective figures of 9.5 per cent and 33 per cent in the control population. The hepatitis B surface antigen positive patients were younger than the negative patients but their treatment outcomes were similar despite the higher incidence of hepatic complications (21 per cent) in the hepatitis B surface antigen positive patients during therapy for lymphomas. None of the clinical parameters analysed appeared to be useful in predicting the development of these complications which included fatal liver failure (5.7 per cent), icteric hepatitis (5.7 per cent) and anicteric hepatitis (9.5 per cent). The high prevalence of hepatitis B surface antigen in our lymphoma patients may be related to the immunosuppressive effect of lymphomas. There is no definite evidence to suggest that hepatitis B infection has an aetiological or promoting role in the pathogenesis of lymphomas. Hepatitis B infection has contributed to the high incidence of hepatic complications during therapy for lymphomas and possible ways of prevention need to be investigated.

Thirteen female patients with lymphomas involving the genital tract were studied. Their median age was 50 years. There were three cases of stage I disease, one stage II and nine stage IV. The gastrointestinal tract was commonly involved in patients with disease in the ovary. The histology was mostly intermediate or high grade according to the Working Formulation. Immunophenotyping was performed in six patients and they were all B-cell tumours. There appeared to have a strong association between gastrointestinal involvement and ovarian disease. All patients received combination chemotherapy with or without additional radiotherapy and the survival of patients with stage I and II disease appeared to be superior to those with stage IV disease. However, the difference observed did not reach statistical significance because of small patient number. It remains uncertain whether lymphomas of the female genital tract by itself carries a poorer prognosis than the nodal lymphomas of comparable stage and histology.

One hundred febrile episodes in 89 neutropenic patients after cytotoxic chemotherapy were randomized to be treated with either ceftazidime or imipenem as initial monotherapy. The clinical characteristics of the two groups of patients were comparable. The response of the fever in patients who received imipenem was significantly better than that in those who received ceftazidime (77 versus 56%, respectively; P = 0.04), especially in those with microbiologically documented infection (81 versus 33%, respectively; P = 0.02). The in vitro susceptibilities and the clinical responses suggested that, with the possible exception of Pseudomonas spp., imipenem was more effective than ceftazidime in treating neutropenic infections caused by both gram-positive and -negative organisms. An additional 23 and 21% of the patients in the ceftazidime and imipenem groups, respectively, responded to the addition of cloxacillin and amikacin following failure of monotherapy. The majority of the treatment failures, relapses, and superinfections were related to resistant infective organisms such as methicillin-resistant Staphylococcus spp. and Pseudomonas spp. or disseminated fungal infections., link_to_subscribed_fulltext

Cognitive deficits in Huntington’s disease (HD) have been attributed to neuronal degeneration within the striatum; however, postmortem and structural imaging studies have revealed more widespread morphological changes. To examine the impact of HD-related changes in regions outside the striatum, we used functional magnetic resonance imaging (fMRI) in HD to examine brain activation patterns using a Simon task that required a button press response to either congruent or incongruent arrow stimuli. Twenty mild to moderate stage HD patients and 17 healthy controls were scanned using a 3 T GE scanner. Data analysis involved the use of statistical parametric mapping software with a random effects analysis model to investigate group differences brain activation patterns compared to baseline. HD patients recruited frontal and parietal cortical regions to perform the task, and also showed significantly greater activation, compared to controls, in the caudal anterior cingulate, insula, inferior parietal lobules, superior temporal gyrus bilaterally, right inferior frontal gyrus, right precuneus/superior parietal lobule, left precentral gyrus, and left dorsal premotor cortex. The significantly increased activation in anterior cingulate–frontal–motor–parietal cortex in HD may represent a primary dysfunction due to direct cell loss or damage in cortical regions, and/or a secondary compensatory mechanism of increased cortical recruitment due to primary striatal deficits. © 2007 Elsevier Ltd. All rights reserved.

Background Following an earlier study in which elderly patients with schizophrenia had their typical antipsychotic medication changed to olanzapine or risperidone, the 61 patients were followed for up to a further six months to see if either treatment was superior in terms of efficacy or side effects. Aims To determine whether either olanzapine or risperidone was superior in terms of efficacy or side effects when treating schizophrenia in late life. Methods Psychiatric symptoms, side effects and quality of life were rated every six weeks for 24 weeks of open label comparative treatment using standard measures. Group differences were examined using analysis of covariance and within-group changes over time were assessed using paired t-tests. Results There were 34 olanzapine and 32 risperidone patients who entered the study, but intention to treat data was only available for 61 of the 66 patients. There were no clinical or demographic differences between the groups. Parkinsonism, positive and negative symptoms of schizophrenia improved in both groups both from baseline switch to olanzapine or risperidone and during the six month follow-up after completion of crossover. No significant differences were seen between groups on most measures. However, patients treated with olanzapine showed a significantly greater improvement in quality of life from baseline compared to risperidone patients. Conclusions Both drugs were well tolerated and their use was associated with fewer symptoms of schizophrenia and less adverse effects than were seen when the patients were taking a typical antipsychotic at baseline. Olanzapine appears to have particular benefit with regard to quality of life. Copyright © 2006 John Wiley & Sons, Ltd.

Disturbances of walking have been described in people with Huntington's disease (HD), although the nature of the deficits have not yet been well defined. The purpose of this investigation was to determine whether people with HD have a deficit in the regulation of footstep timing during walking. The footstep patterns of 30 people with HD and 30 matched comparisons were measured at self-selected slow, preferred, and fast speeds. Subjects were also instructed to match their footsteps to auditory metronome cues set at 80 and 120 beats per minute. Gait speed, cadence, stride length, and double limb support as a percentage of the gait cycle were measured using a computerized foot-switch system. People with HD demonstrated a disorder in their ability to regulate cadence, manifest as a reduced step frequency when walking at preferred speed and when required to increase their speed. For all walking conditions, people with HD had increased variability of footstep cadence. They also had difficulty synchronizing their footstep timing to an auditory cue. For all walking conditions, people with HD had reduced stride length. Thus, in HD, there is a disorder in the regulation of footstep timing, with increased variability, a restricted cadence range, difficulty synchronizing footsteps to an auditory cue and reduced stride length. The exact neural correlates of this timing disorder are yet to be determined.

We investigated both motor overflow and ability to control voluntary movement in patients with Huntington's disease (HD). We hypothesised that, compared with controls, overflow would be significantly greater in HD participants and that they would exhibit poorer control of voluntary movement. In a finger flexion task, participants had to maintain target forces representing 25, 50, or 75% of the maximum strength capacity for whichever finger was performing the task; overflow was measured in the corresponding finger of the non-responding hand. HD participants exhibited significantly greater motor overflow than controls, and more difficulty controlling the target force with the active hand. In addition, the degree of overflow in HD participants positively correlated with overall UHDRS motor symptom severity. The presence of exacerbated motor overflow in HD, and its correlation with symptom severity, is an important finding worthy of further investigation.

The vestibulo-ocular reflex (VOR) stabilizes gaze during movement, in conjunction with other afferent information: visual, proprioceptive, and somaesthetic. The reflex can either be augmented or suppressed, depending on visual requirements, and undergoes long-term adaptation to compensate for physical changes in the subject. Importantly, over relatively short periods of time, the VOR should function consistently under the same circumstances. This study examines VOR function in patients with Huntington's disease (HD), with a view to investigating cortical influences on the reflex. Horizontal eye movements were recorded in 9 patients with HD and 7 normal subjects, using the scleral search coil technique, in response to high frequency, unpredictable head rotations imposed manually. To establish base VOR function, recordings were made in darkness, without instruction, before and after wearing x2 magnifying lenses for a period of 2 hours to adapt the reflex. Recordings were also made before adaptation, while fixating a stationary visual target (VOR augmentation), and while fixating a target moving with the head (VOR suppression). Although results suggest that the VOR is preserved in HD, with relatively normal gain values and appropriate augmentation and suppression of the reflex with visual input, patients were unable to adapt the VOR to altered visual conditions. This represents a novel finding in HD and suggests that cortical structures compromised in HD exert influences on the long-term adaptation of the VOR.

Eye movement abnormalities can be distinctive and suggestive of a specific pathophysiology. To further investigate the deficits in the control of saccades in patients with Huntington's disease (HD), we investigated the ability of 11 HD patients and 11 matched controls to perform visually-guided saccades. We adopted reflexive saccade tasks involving predictable and unpredictable sequences, at different amplitudes of target step (10 degrees, 20 degrees, 30 degrees, 40 degrees ), as well as voluntary self-paced saccades. Prolongation of initiation was observed in the HD group as the target amplitude of predictable saccades increased. During the self-paced saccade task, the HD patients had increased intersaccadic intervals, performed fewer saccades in the allocated time and displayed an increased temporal variability in comparison to the controls. Furthermore, hypometric primary saccades, and an increased number of corrective saccades, were observed during both reflexive and voluntary saccades in the HD group. The delayed initiation of large saccades, deficits in voluntary, self-paced saccades, impaired saccadic accuracy and increased corrective saccades in HD, were interpreted in light of other ocular motor and limb studies, and appear to be due to damage to the fronto-striatal loop, including the supplementary eye fields, as well as possible brainstem and cerebellar involvement.

This experiment sought to quantify the extent to which patients with Huntington disease (HD) have difficulties in orienting attention, via a vibrotactile version of a Posner-type cost-benefit paradigm.Participants were required to push a button in response to a vibration delivered to the index finger of either hand. Prior to each stimulus vibration, a precue (valid, neutral, or invalid) was delivered to the finger. Benefits and costs were calculated from valid and invalid precues.Although patients with HD were overall slower than the controls, their performance was no different; both patients and controls demonstrated increased benefits from valid compared with invalid and neutral cues. Of interest was the finding that patients, unlike controls, performed significantly slower with the cue presented to the left compared with the right side. The crossed arm configuration proved to be too difficult for the patients with HD, and thus an analysis on these data was not permitted.Patients may experience difficulties in allocating attentional resources toward their left nonpreferred hand. Overall, findings demonstrate that patients with HD, with minimal caudate damage at early stages of disease onset, may not experience problems in their ability to orient attention.

Huntington's disease patients perform automatic movements in a bradykinetic manner, somewhat similar to patients with Parkinson's disease. Cortical activity relating to the preparation of movement in Parkinson's disease is significantly improved when a cognitive strategy is used. It is unknown whether patients with Huntington's disease can utilise an attentional strategy, and what effect this strategy would have on the premovement cortical activity. Movement-related potentials were recorded from 12 Huntington's disease patients and controls performing externally cued finger tapping movement, allowing an examination of cortical activity related to movement performance and bradykinesia in this disease. All subjects were tested in two conditions, which differed only by the presence or absence of the cognitive strategy. The Huntington's disease group, unlike controls, did not produce a rising premovement potential in the absence of the strategy. The Huntington's disease group did produce a rising premovement potential for the strategy condition, but the early slope of the potential was significantly reduced compared with the control group's early slope. These results are similar to those found previously with Parkinson's disease patients. The strategy may have put the task, which previously might have been under deficient automatic control, under attentional control.

In the past Alzheimer disease (AD) has been presented to elderly people and their families as a very frightening condition, based on media representation of the worst possible case scenarios.The current status of pharmacological and psychosocial Intervention in Alzheimer disease is reviewed from the recent literature.In the last decade, the picture of AD has turned to one of hope and optimism as a result of advances in developing pharmacological and psychological management.

Huntington's Disease (HD) is a serious dominantly inherited neurodegenerative disorder for which there are no current treatments. Open label and animal studies have suggested that highly unsaturated fatty acids (HUFAs) may be beneficial. Seventeen patients with HD were entered into a randomised, placebo-controlled, double blind trial of HUFA therapy. Patients were assessed on the Rockland-Simpson Dyskinesia Rating Scale (RSDRS) and the Unified Huntington's Disease Rating Scale (UHDRS). On the RSDRS and the UHDRs motor scale patients on HUFA treatment improved while those on placebo deteriorated, with a significant difference between the two groups on the RSDRS. A similar trend was noted on the UHDRS functional performance scales. Little change was seen on the neuropsychology scales. There were no treatment-related adverse events. This is the first time that a significant improvement has been noted in a randomised trial in HD. The results are consistent with open label observations; a second placebo-controlled study in end-stage patients, and a study in a transgenic mouse model of HD.