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Biomedical subjects

A J Lees

Publications and source records attributed to A J Lees.

At least 109 records · Page 6Linked to original sources
PubMed1999

Parkinson's syndrome after closed head injury: a single case report.

A 36 year old man, who sustained a skull fracture in 1984, was unconscious for 24 hours, and developed signs of Parkinson's syndrome 6 weeks after the injury. When assessed in 1995, neuroimaging disclosed a cerebral infarction due to trauma involving the left caudate and lenticular nucleus. Parkinson's syndrome was predominantly right sided, slowly progressive, and unresponsive to levodopa therapy. Reaction time tests showed slowness of movement initiation and execution with both hands, particularly the right. Recording of movement related cortical potentials suggested bilateral deficits in movement preparation. Neuropsychological assessment disclosed no evidence of major deficits on tests assessing executive function or working memory, with the exception of selective impairments on the Stroop and on a test of self ordered random number sequences. There was evidence of abulia. The results are discussed in relation to previous literature on basal ganglia lesions and the effects of damage to different points of the frontostriatal circuits.

Adult↗
PubMed1999

Impairment of EEG desynchronisation before and during movement and its relation to bradykinesia in Parkinson's disease.

OBJECTIVE: It has been suggested that the basal ganglia act to release cortical elements from idling (alpha) rhythms so that they may become coherent in the gamma range, thereby binding together those distributed activities necessary for the effective selection and execution of a motor act. This hypothesis was tested in 10 patients with idiopathic Parkinson's disease. METHODS: Surface EEG was recorded during self paced squeezing of the hand and elbow flexion performed separately, simultaneously, or sequentially. Recordings were made after overnight withdrawal of medication and, again, 1 hour after levodopa. The medication related improvement in EEG desynchronisation (in the 7.5-12.5 Hz band) over the 1 second before movement and during movement were separately correlated with the improvement in movement time for each electrode site. Correlation coefficients (r) > 0.632 were considered significant (p<0.05). RESULTS: Improvement in premovement desynchronisation correlated with reduction in bradykinesia over the contralateral sensorimotor cortex and supplementary motor area in flexion and squeeze, respectively. However, when both movements were combined either simultaneously or sequentially, this correlation shifted anteriorly, to areas overlying prefrontal cortex. Improvement in EEG desynchronisation during movement only correlated with reduction in bradykinesia in two tasks. Correlation was seen over the supplementary motor area during flexion, and central prefrontal and ipsilateral premotor areas during simultaneous flex and squeeze. CONCLUSIONS: The results are consistent with the idea that the basal ganglia liberate frontal cortex from idling rhythms, and that this effect is focused and specific in so far as it changes with the demands of the task. In particular, the effective selection and execution of more complex tasks is associated with changes over the prefrontal cortex.

Aged↗
PubMed1999

The tau gene A0 polymorphism in progressive supranuclear palsy and related neurodegenerative diseases.

Progressive supranuclear palsy is characterised pathologically by the deposition of neurofibrillary tangles consisting of tau protein. Patients with the disease have been reported to have a more frequent occurrence of one allele of an intronic polymorphism of the tau gene. Other diseases which may involve tau deposition include frontotemporal dementia and corticobasal degeneration. This polymorphism has been studied in a series of subjects with progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia, idiopathic Parkinson's disease, and normal controls to (1) confirm this association in a large series and (2) to investigate a possible role for this association in other disorders which involve tau deposition. The results confirm the finding of an overrepresentation of the A0 allele and the A0/A0 genotype in patients with progressive supranuclear palsy, in the largest series reported to date. The A0 allele was found in 91% of patients with progressive supranuclear palsy as opposed to 73% of controls (p<0.001) and the A0/A0 genotype was seen in 84% of patients as compared with 53% of controls (p<0.01). There was no significant difference between patients with Parkinson's disease, frontotemporal dementia, or corticobasal degeneration, and controls. The A0 allele may have a direct effect on tau isoform expression in progressive supranuclear palsy or it may be in linkage disequilibrium with an adjacent determinant of tau gene expression. The explanation for this difference between a predisposition factor to progressive supranuclear palsy and the other conditions may lie in the molecular pathology of these diseases.

Alleles↗
PubMed1999

Unilateral pallidotomy for Parkinson's disease: results after more than 1 year.

OBJECTIVE: To examine follow up results of unilateral ventral medial pallidotomy in 22 patients with advanced Parkinson's disease more than 1 year after the operation in comparison with their results (previously reported) at 3 months. METHODS: Twenty patients who had undergone unilateral pallidotomy were assessed with the core assessment programme for intracerebral transplantation (CAPIT) protocol preoperatively, at 3 months postoperatively, and again after a median postoperative follow up of 14 months. Two further patients had only one evaluation 3 months postoperatively. RESULTS: The reduction of contralateral dyskinesias (median 67%) at 3 months was slightly attenuated after 1 year to 55% (both p<0.001 compared with baseline). A less pronounced effect on ipsilateral and axial dyskinesias decreased from 39% to 33% (p<0.005 and p<0.01), and from 50% to 12.5% (p<0.001 and p<0.01), respectively. However, there was no significant change between the 3 month and the follow up assessment. The modest improvement of the contralateral unified Parkinson's disease rating scale (UPDRS) motor score in the "off" state remained improved compared with preoperative levels, but less significantly (26%, p<0.001, and 18%, p<0.01). The activities of daily living (ADL) subscore of the UPDRS in the off state remained improved with median changes of 23% and 22% at follow up (both p<0. 005). There was no significant improvement of "on" state or ipsilateral off state motor scores. Median modified Hoehn and Yahr scores in off and on state were unchanged, as was the time spent off. Speech in off had significantly deteriorated by 1 year after the operation. CONCLUSIONS: The beneficial effects of unilateral pallidotomy persist for at least 12 months and, dyskinesias are most responsive to this procedure.

Adult↗
PubMed1999

Bradykinesia akinesia inco-ordination test (BRAIN TEST): an objective computerised assessment of upper limb motor function.

OBJECTIVES: A simple and rapid computerised keyboard test, based on the alternating finger tapping test, has been developed to quantify upper limb motor function. The test generates several variables: (1) kinesia score: the number of keystrokes in 60 seconds; (2) akinesia time: cumulative time that keys are depressed; (3) dysmetria score: a weighted index calculated using the number of incorrectly hit keys corrected for speed; (4) incoordination score: a measure of rhythmicity which corresponds to the variance of the time interval between keystrokes. METHODS: The BRAIN TEST(Copyright ) was assessed on 35 patients with idiopathic Parkinson's disease, 12 patients with cerebellar dysfunction, and 27 normal control subjects. RESULTS: The mean kinesia scores of patients with Parkinson's disease or cerebellar dysfunction were significantly slower than normal controls (Parkinson's disease=107 (SD 28) keys/min v cerebellar dysfunction=86+/- (SD 28) v normal controls=182 (SD 26), p<0.001) and correlated with the UPDRS (r =-0.69, p<0.001). The akinesia time is very insensitive and was only abnormal in patients with severe parkinsonism. The median dysmetria (cerebellar dysfunction=13.8 v Parkinson's disease=6.1 v normal controls=4.2, p=0.002) and inco-ordination scores (cerebellar dysfunction=5.12 v Parkinson's disease=0.84 v normal controls=0.15, p=0.002) were significantly higher in patients with cerebellar dysfunction, in whom the dysmetria score correlated with a cerebellar disease rating scale (r=0.64, p=0.02). CONCLUSION: The BRAIN TEST(Copyright ) provides a simple, rapid, and objective assessment of upper limb motor function. It assesses speed, accuracy, and rhythmicity of upper limb movements regardless of their physiological basis. The results of the test correlate well with clinical rating scales in Parkinson's disease and cerebellar dysfunction. The BRAIN test will be useful in clinical studies. It can be downloaded from the Internet ().

Adult↗
PubMed1999

Progressive supranuclear palsy (Steele-Richardson-Olszewski disease).

Progressive supranuclear palsy is a neurodegenerative disease which affects the brainstem and basal ganglia. Patients present with disturbance of balance, a disorder of downward gaze and L-DOPA-unresponsive parkinsonism and usually develop progressive dysphagia and dysarthria leading to death from the complications of immobility and aspiration. Treatment remains largely supportive but, potentially, treatments based on cholinergic therapy may be useful. As in Alzheimer's disease, the neuronal degeneration is associated with the deposition of hyperphosphorylated tau protein as neurofibrillary tangles but there are important distinctions between the two diseases. Evidence from familial fronto-temporal dementia with parkinsonism linked to chromosome 17 suggests that tau protein deposition is a primary pathogenic event in some neurodegenerative diseases. The understanding of the mechanism of tau deposition in progressive supranuclear palsy is likely to be of importance in unravelling its aetiology.

Alzheimer Disease↗
PubMed1999

Use of apomorphine in Parkinson's disease.

Apomorphine is a dopamine agonist administered subcutaneously as intermittent injections or in a continuous infusion. It is useful in managing advanced Parkinson's disease, and provides an alternative to neurosurgical procedures. This review summarizes indications and practical guidelines for its use.

Apomorphine↗
PubMed1998

Basal ganglia neuronal nitric oxide synthase mRNA expression in Parkinson's disease.

Expression of nitric oxide synthase (NOS) mRNA in post mortem brain was studied in putamen, globus pallidus and subthalamic nucleus (STN) of neurologically normal control subjects and patients with Parkinson's disease (PD) using in situ hybridization histochemistry. In PD, a significant increase in NOS mRNA expression was observed in the dorsal two-thirds of the STN with respect to the ventral one-third of the STN. A significant increase in NOS mRNA expression per cell in the medial medullary lamina of the globus pallidus was also observed in PD. NOS mRNA expression was significantly reduced in PD putamen. These findings provide evidence of increased activity of STN neurotransmitter systems in PD and demonstrate for the first time in any species that basal ganglia nitric oxide systems can be selectively regulated in response to changes in dopaminergic input.

Aged↗
PubMed1998

Investigation by Parkinson's Disease Research Group of United Kingdom into excess mortality seen with combined levodopa and selegiline treatment in patients with early, mild Parkinson's disease: further results of randomised trial and confidential inquiry.

OBJECTIVE: To determine whether the excess mortality observed in patients who received both levodopa and selegiline in a randomised trial could be explained by revised diagnosis of Parkinson's disease, autonomic or cardiovascular effects, more rapid disease progression, or drug interactions. DESIGN: Open randomised trial and blind comparison and reclassification of the cause of death of patients who were recruited from 93 hospitals between 1985 and 1990 and who had died before December 1993 in arms 1 and 2. SETTING: United Kingdom. SUBJECTS: 624 patients with early Parkinson's disease who were not receiving dopaminergic treatment and a subgroup fo 120 patients who died during the trial. INTERVENTIONS: Levodopa and a dopa carboxylase inhibitor (arm 1), levodopa and a dopa decarboxylase inhibitor in combination with selegiline (arm 2), or bromocriptine alone (arm 3). MAIN OUTCOME MEASURES: All cause mortality for 520 subjects in arms 1 and 2 and for 104 subjects who were randomised into these arms from arm 3. Cause specific mortality for people who died in the original arms 1 and 2 on the basis of the opinion of a panel, revised diagnosis and disability ratings, evidence from clinical records of either autonomic or cardiovascular episodes, other clinical features before death, and drug interactions. RESULTS: After extended follow up (mean 6.8 years) until the end of September 1995, when arm 2 was terminated, the hazard ratio for arm 2 compared with arm 1 was 1.32 (95% confidence interval 0.98 to 1.79). For subjects who were randomised from arm 3 the hazard ratio for arm 2 was 1.54 (0.83 to 2.87). When all subjects were included the hazard ratio was 1.33 (1.02 to 1.74) and after adjustment for other baseline factors it was 1.30 (0.99 to 1.72). The excess mortality seemed to be greatest in the third and fourth year of follow up. Cause specific death rates showed an excess of deaths from Parkinson's disease only (hazard ratio 2.5 (1.3 to 4.7)). No significant differences were found for revised diagnosis, disability rating scores, autonomic or cardiovascular events, other clinical features, or drug interactions. Patients who died in arm 2 were more likely to have had possible dementia and a history of falls before death compared with those who died in arm 1. CONCLUSION: The results consistently show excess mortality in patients treated with combined levodopa and selegiline. Revised diagnosis, autonomic or cardiovascular events, or drug interactions could not explain this finding, but falls and possible dementia were more common in arm 2. The results do not support combined treatment in patients with newly diagnosed Parkinson's disease. In more advanced disease, combined treatment should perhaps be avoided in patients with postural hypotension, frequent falls, confusion, or dementia.

Antiparkinson Agents↗
PubMed1998

Acute movement disorders with bilateral basal ganglia lesions in uremia.

Acute and subacute extrapyramidal movement disorders are rarely reported in uremic patients. We report three such cases with basal ganglia lesions. All three had advanced renal failure with high serum creatinine levels. One of the patients had a history of ischemic heart disease and acute pulmonary edema with hypoxemia. Another patient had experienced arterial hypotension during previous hemodialysis. The third had prominent metabolic acidosis. One of the patients developed generalized dyskinesias, whereas the other two developed gait disturbances. Neuroimaging studies in all three cases showed bilateral changes in the basal ganglia. The natural history was self-limiting with gradual improvement. Diminution of the basal ganglia lesions was demonstrated on follow-up imaging in two of the three cases. We conclude that acute or subacute movement disorders with bilateral basal ganglia lesions may occur in uremia. Hypoperfusion with global brain ischemia and selective vulnerability of the basal ganglia to uremic toxins may account for these lesions.

Acute Disease↗
PubMed1998

Conjugates of catecholamines with cysteine and GSH in Parkinson's disease: possible mechanisms of formation involving reactive oxygen species.

Oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine (DA) to generate semiquinones/quinones, oxygen radicals, and other reactive oxygen species may play a role in neuronal cell death in Parkinson's disease (PD). In particular, semiquinones/quinones can form conjugates with thiol compounds such as GSH and cysteine. Exposure of L-DOPA, DA, and other catecholamines to a system generating O2.- radical led to O2(.-)-dependent depletion of added GSH (or cysteine), accompanied by the formation of thiol-DA or -DOPA adducts as detected by HPLC. Superoxide could additionally cause destruction of these adducts. Iron or copper ions could also promote conjugate formation between GSH or cysteine and DA and L-DOPA, especially if H2O2 was present. We applied HPLC to measure glutathionyl and cysteinyl conjugates of L-DOPA, DA, and 3,4-dihydroxyphenylacetic acid (DOPAC) in postmortem brain samples from PD patients and normal control subjects. Conjugates were detected in most brain areas examined, but levels were highest in the substantia nigra and putamen. In most regions, adduct levels were lower in PD, but there were significant increases in cysteinyl adducts of L-DOPA, DA, and DOPAC in PD substantia nigra, suggesting that acceleration of L-DOPA/DA oxidation occurs in PD, although we cannot say if this is a primary feature of the disease or if it is related to therapy with L-DOPA. In vitro, conjugate formation could be inhibited by the dithiol dihydrolipoate but not by its oxidised form, lipoic acid.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

A study of medial pallidotomy for Parkinson's disease: clinical outcome, MRI location and complications.

We have studied the effects of unilateral ventral medial pallidotomy in 26 patients with medically intractable Parkinson's disease with marked drug-induced dyskinesias. Preoperatively, all patients were assessed during one 5-day admission according to the Core Assessment Programme for Intracerebral Transplantation (CAPIT) protocol, including rating in the 'practically defined off' and 'best on' states before and during a single-dose levodopa challenge. Motor performance was assessed with subset categories of the Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests and a standard dyskinesia rating scale. Pallidotomy was performed under stereotaxic CT guidance with intra-operative extracellular microelectrode recording made from the basal ganglia. All patients were re-assessed 3 months postoperatively and a subgroup (n = 9) have so far also been re-assessed after 1 year. Pre- and postoperative performance scores were compared in order to determine which categories of performance improved postoperatively. Significance was accepted at P < 0.005 in order to take into account the multiple number of comparisons performed. Patient medication was compared pre- and postoperatively and the morbidity associated with surgery was also recorded. The most significant improvement postoperatively was the diminution of 'on' dyskinesias contralaterally (67%, P = 0.0001); however, ipsilateral (45%, P = 0.0006) and axial (50%, P = 0.0008) dyskinesias also improved. Contralateral to pallidotomy, the median 'off' motor UPDRS score improved by 27% (P = 0.001) and a significant improvement was also observed in contralateral rigidity by 25% (P = 0.001). There were trends towards improvement in contralateral tremor (33%, P = 0.016) and bradykinesia (24%, P = 0.013) scores. Ipsilateral rigidity improved by 22% (P = 0.005), but other ipsilateral motor scores did not alter significantly. The 'off' gait/postural instability score and 'off' walking time showed marginally significant improvements by 7% (P = 0.007) and 29% (P = 0.014), respectively. On medication, no significant postoperative improvements in parkinsonism were detected. Anti-parkinsonian medication increased by 11% postoperatively. In the subgroup who were available for assessment 1 year postoperatively, responses were generally maintained. Two (7.7%) of the 26 patients had fatal complications (one cerebral haemorrhage and one haemorrhagic infarct) directly related to surgery. Among the remaining 24 patients, four (15.4% of the total 26) had major complications (two persisting and two transient). Ten patients (38.5%) had minor complications. The majority of the complications (major and minor) occurred in the earlier operated patients and the complication rate subsequently declined with increasing operative experience. The remaining 10 patients (38.5%) had no significant side-effects. One of these 10 patients died from an incidental malignant glioma 6 months postoperatively. These findings confirm that levodopa-induced dyskinesias are dramatically reduced following ventral medial pallidotomy and constitute the principal indication for pallidotomy. Improvements in underlying parkinsonism were of smaller magnitude. Pallidotomy may also offer some patients an opportunity to increase antiparkinsonian medication. Patient selection for medial pallidotomy should, therefore, be based largely on anticipated improvements in levodopa-induced dyskinesias, but this must be balanced against the associated morbidity and mortality.

Aged↗
PubMed1998

Continuous subcutaneous waking day apomorphine in the long term treatment of levodopa induced interdose dyskinesias in Parkinson's disease.

OBJECTIVES: To determine whether continuous waking day dopaminergic stimulation with the dopamine agonist apomorphine can reduce levodopa induced dyskinesias in Parkinson's disease METHODS: 19 patients with severe unpredictable refractory motor fluctuations and functionally disabling levodopa induced dyskinesias were treated with continuous subcutaneous apomorphine monotherapy for a minimum duration of 2.7 years RESULTS: A mean 65% reduction in dyskinetic severity and a mean 85% reduction in frequency and duration occurred. On discontinuing levodopa a concomitant reduction in off period time was also seen (35% of waking day "off" reduced to 10%) CONCLUSION: Continuous waking day dopaminergic stimulation with apomorphine reset the threshold for dyskinesias and led to a pronounced reduction in their frequency. Apomorphine should be considered as a less invasive alternative to pallidotomy or deep cerebral stimulation in controlling levodopa induced interdose dose dyskinesias.

Aged↗
PubMed1998

Further studies using higher doses of botulinum toxin type F for torticollis resistant to botulinum toxin type A.

OBJECTIVE: A previous study of botulinum toxin type F (BTX-F) treatment for torticollis had shown a dose of 520 MU to be effective, but for a much shorter duration than is usual with botulinum toxin type A (BTX-A). The objective was to assess the effect of a higher dose of BTX-F. METHODS: Four of the previously treated patients, plus an additional patient, were treated with a higher dose of 780 MU BTX-F. All were secondary nonresponders to BTX-A due to neutralising antibodies. A test injection of 40 MU BTX-F was also given into the extensor digitorum brevis muscle (EDB), to examine the time course of the biological effect of the toxin electrophysiologically. Patients were followed up at two, four, eight, and 12 weeks. RESULTS: All patients reported subjective improvement lasting from seven to 11 (mean 8.6) weeks accompanied by a significant reduction in mean clinical severity scores at two weeks. Four patients had pain which was substantially reduced. The electrophysiological studies confirmed biological sensitivity to the toxin in all patients, showing a significant change beginning at two weeks and returning to baseline at 12 weeks. The time course of this effect paralleled roughly that of the clinical response. The four patients who had previously received 520 MU BTX-F reported that the response was better and longer in duration with 780 MU. Dysphagia was more common than reported with the lower dose. CONCLUSION: Better results are possible with higher doses of BTX-F but the duration of benefit is still shorter than with BTX-A, seemingly due to a shorter duration of neuromuscular junction blockade.

Adult↗
PubMed1998

Clinical usefulness of magnetic resonance imaging in multiple system atrophy.

OBJECTIVES: To determine the sensitivity, specificity, and positive predictive values of a selection of abnormal findings in the putamen and infratentorial structures on routine magnetic resonance imaging for distinguishing between multiple system atrophy, idiopathic Parkinson's disease, and age matched controls. PATIENTS AND METHODS: Two neuroradiologists blindly and independently rated axial T2 weighted and proton density MRI of 44 patients with multiple system atrophy, 47 patients with idiopathic Parkinson's disease, and 45 controls. High field (1.5 T) scans were available in 16 patients with multiple system atrophy, 15 patients with idiopathic Parkinson's disease, and 16 controls. All other patients had 0.5 T scans. RESULTS: On both 0.5 and 1.5 T scans the following items had high specificity but low sensitivity: putaminal atrophy, a hyperintense putaminal rim, and infratentorial signal change. Finding any infratentorial abnormality gave higher sensitivity but lower specificity. Putaminal isointensity or hypointensity relative to globus pallidus, absolute putaminal hypointensity, and altered size of the olives were not useful discriminators. The overall sensitivity was 73% on 0.5 T and 88% on 1.5 T scans. The specificities of these findings for multiple system atrophy in comparison to idiopathic Parkinson's disease and controls on 0.5 T were 95% and 100% respectively, and on 1.5 T were 93% and 91% respectively. Finding any of the described abnormalities on MRI gave a positive predictive value of 93% on the 0.5 T machine, and 85% on the 1.5 T scanner.

Adult↗