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Biomedical subjects

A J Lees

Publications and source records attributed to A J Lees.

At least 91 records · Page 5Linked to original sources
PubMed2000

Differentiation of atypical parkinsonian syndromes with routine MRI.

OBJECTIVE: To evaluate the use of routine MRI in differentiating between patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD) and control subjects. METHODS: Two neuroradiologists rated blindly and independently axial T2-weighted and proton density MR images of 54 patients with MSA, 35 patients with PSP, 5 patients with CBD, and 44 control subjects. RESULTS: More than 70% of patients with PSP and more than 80% of patients with cerebellar predominant MSA could be classified correctly with 0.5-T or 1.5-T scans, and no patient in these groups was misclassified. In the remaining patients an unequivocal differentiation could not be made. However, only approximately 50% of patients with parkinsonism-predominant MSA could be classified correctly, and 19% of them (all of whom had had 0.5-T scans) were misclassified. CONCLUSIONS: Characteristic findings on routine MRI, either 1.5 T or 0.5 T, can contribute to the identification of MSA and PSP. However, in a minority of patients no unequivocal diagnosis can be made using MRI findings alone.

Adult↗
PubMed2000

Sign language tics in a prelingually deaf man.

Gilles de la Tourette syndrome is characterized by vocal and motor tics starting in childhood. Vocal tics may be either noises or words, and the vocal language tics may consist of obscenities (coprolalia) and repetitions of speech that has been heard (echolalia). We describe a prelingually deaf man who has the full array of tics seen in Gilles de la Tourette syndrome, but in whom vocal language tics are replaced by equivalent sign language tics. This is, to our knowledge, the first report of sign language tics in a person with prelingual deafness. The implications of this phenomenon for the separation between language and ideas in tics and the equivalence of sign language to spoken language is discussed.

Adult↗
PubMed2000

Movement disorders in 30 patients with tuberculous meningitis.

BACKGROUND: Movement disorders may appear during tuberculous meningitis (TbM). OBJECTIVE: To investigate the variety of movement disorders seen in TbM and consider possible pathogenic mechanisms. DESIGN: We established two diagnostic categories for TbM: definite and probable. All patients were examined clinically and with laboratory tests, computed tomographic scan, or magnetic resonance imaging. SETTING: A university hospital in Quito, Ecuador. RESULTS: Thirty of 180 consecutively studied patients with TbM developed movement disorders. Twenty-four months after treatment was completed, we determined a prognosis for the patients. Seven patients had chorea, three dystonia, and 20 tremor. One of the patients with tremor also had myoclonus and one with dystonia had tremor. The average age of the patients with chorea was lower than that of the patients with dystonia and tremor. Two patients with chorea, one with dystonia, and three patients with tremor died. The patients with chorea and dystonia had more severe disease. We found little correlation between the type, distribution, or severity of abnormal movements and the computed tomography scan or magnetic resonance image findings. CONCLUSIONS: Tremor is the most common movement disorder seen in the course of TbM. Chorea is more frequently found in young children. Deep vascular lesions are more common among patients with movement disorders.

Adolescent↗
PubMed2000

Neuronal intranuclear inclusion disease and juvenile parkinsonism.

Juvenile parkinsonism (onset age <20 yrs) is uncommon and few cases with neuropathologic confirmation have been reported. We present the case of a 17-year-old boy who presented with asymmetric arm tremor and bulbar symptoms. His paternal great aunt had parkinsonism with onset at age 22 years. Examination revealed parkinsonism in the absence of additional neurologic signs except for delayed pupillary responses to light. He responded well to levodopa but developed motor fluctuations and disabling dyskinesias after 3 years of treatment. Following attempted withdrawal of levodopa at age 24 years, he developed severe aspiration pneumonia complicated by cardiorepiratory arrests and he died 6 months later. At autopsy, the dominant histologic feature was wide-spread neuronal hyaline intranuclear inclusions. Neuronal depletion was observed in the substantia nigra, locus ceruleus, and, to a lesser extent, in the frontal cortex, and inclusions were particularly prominent in these areas. Inclusions were immunoreactive for ubiquitin and were typical of those seen in neuronal intranuclear inclusion disease (NIID), a rare, multisytem neurodegenerative disease. NIID should be considered in the differential diagnosis of juvenile parkinsonism. A link between NIID and hereditary neurodegenerative disorders characterized by expanded polyglutamine tracts is supported by the similar appearance of intranuclear inclusions in both conditions and by a family history in some cases of NIID.

Adolescent↗
PubMed2000

Physiological, pharmacological and neurohormonal assessment of autonomic function in progressive supranuclear palsy.

The clinical features of progressive supranuclear palsy (PSP) overlap with other parkinsonian syndromes, including multiple system atrophy (MSA). Autonomic dysfunction is a characteristic of MSA, but has also been described in PSP. We therefore report results from a series of physiological studies of cardiovascular autonomic function in 35 PSP and 20 MSA subjects, and 26 age-matched healthy control subjects. The response to growth hormone-clonidine testing, a neuropharmacological assessment of central adrenoceptor function, was also assessed in 14 PSP and 10 MSA subjects, and compared with 10 controls. None was on medication which may have affected the results. Orthostatic hypotension did not occur in PSP subjects or controls, unlike MSA subjects. Overall there was no evidence of sympathetic vasoconstrictor failure in PSP subjects, unlike MSA subjects, although the pressor response to mental arithmetic was reduced. Cardiac parasympathetic function was affected in only a minority (three of 35) of PSP subjects and was abnormal in MSA subjects. After clonidine administration, growth hormone rose in PSP subjects (median increase 4.3; interquartile range 1.8-7.8 mU/l) and controls, unlike MSA subjects (0.9; 0.3-2.4 mU/l; P < 0.005, Mann-Whitney U-test). In conclusion, in PSP subjects, responses to both physiological and pharmacological tests provided evidence against widespread autonomic dysfunction; this differed markedly from MSA subjects. Thus, cardiovascular autonomic dysfunction should be an exclusionary feature in the diagnosis of PSP.

Adrenergic alpha-Agonists↗
PubMed2000

An ambulatory dyskinesia monitor.

OBJECTIVES: New treatments are now becoming available for the management of levodopa induced dyskinesias in Parkinsons's disease. However, assessment of their efficacy is limited by the inadequacies of current methods of dyskinesia measurement. The objective was to develop and validate a portable device capable of objectively measuring dyskinesias during normal daily activities. METHODS: A portable device was developed based on a triaxial accelerometer, worn on the shoulder, and a data recorder that can record levodopa induced dyskinesias. A computer program plots raw acceleration and acceleration over 0.5 Hz frequency bands against time. The acceleration in the different bands can then be compared with the raw acceleration trace, enabling identification and exclusion of confounding activities such as tremor and walking, which have a characteristic appearance on the trace. The validity of this device was assessed on 12 patients and eight age matched controls by comparing accelerations in the 1-3 Hz frequency band with established clinical dyskinesia rating scales. While wearing the monitor, subjects were videorecorded sitting and during dyskinesia provocation tasks, including mental activation tasks, eating, drinking, writing, putting on a coat, and walking. The dyskinesias were graded with both modified abnormal involuntary movement (AIM) and Goetz scales. The clinical ratings were then compared with the mean acceleration scores. RESULTS: Acceleration in the 1-3 Hz frequency band correlated well against both scales, during all individual tasks. Acceleration produced by normal voluntary activity (with the exception of walking, which produced large accelerations, even in controls) was small compared with dyskinetic activity. With walking excluded, the mean acceleration over the rest of the recording time correlated strongly with both the modified AIM (Spearman's rank (r=0.972, p<0.001) and Goetz (r=0.951, p<0.001) scales. CONCLUSIONS: This method provides an accurate, objective means for dyskinesia assessment, and compares favourably with established methods currently used.

Adult↗
PubMed2000

Hedonistic homeostatic dysregulation in patients with Parkinson's disease on dopamine replacement therapies.

Hedonistic homeostatic dysregulation is a neuropsychological behavioural disorder associated with substance misuse and addiction. The disorder has been recognised as a consequence of dopamine replacement therapy (DRT) in 15 patients with Parkinson's disease. The syndrome typically develops in male patients with early onset Parkinson's disease, and can occur with orally and subcutaneously administered DRT. These patients take increasing quantities of their DRT, despite increasingly severe drug induced dyskinesias, and may develop a cyclical mood disorder with hypomania or manic psychosis. There is impairment of social and occupational functioning. Tolerance develops to mood elevating effects of DRT and a negative affective withdrawal state occurs if the drugs are withdrawn or doses decreased. The clinical features and guidelines for managing this syndrome are discussed. A set of diagnostic criteria for further investigating this condition is proposed.

Adult↗
PubMed2000

Pattern of premature degenerative changes of the cervical spine in patients with spasmodic torticollis and the impact on the outcome of selective peripheral denervation.

OBJECTIVES: To characterise the pattern of and risk factors for degenerative changes of the cervical spine in patients with spasmodic torticollis and to assess whether these changes affect outcome after selective peripheral denervation. METHODS: Preoperative CT of the upper cervical spine of 34 patients with spasmodic torticollis referred for surgery were reviewed by two radiologists blinded to the clinical findings. Degenerative changes were assessed for each joint separately and rated as absent, minimal, moderate, or severe. Patients were clinically assessed before surgery and 3 months postoperatively by an independent examiner using standardised clinical rating scales. For comparison of means a t test was carried out. To determine whether an association exists between the side of degenerative changes and type of spasmodic torticollis a chi(2) test was used. Changes in severity, disability, and pain before and after surgery were calculated using a Wilcoxon matched pairs signed ranks test. RESULTS: Fourteen out of 34 patients had moderate or severe degenerative changes. They were predominantly found at the C2/C3 and C3/C4 level and were significantly more likely to occur on the side of the main direction of the spasmodic torticollis (p = 0.015). There was no significant difference in age, sex, duration of torticollis, overall severity, degree of disability, or pain between the group with either no or minimal changes and the group with moderate or severe changes. However, in the second group the duration of inadequate treatment was longer (10.1 v 4.8 years; p=0.009), head mobility was more restricted (p = 0.015), and head tremor was more severe (p = 0.01). At 3 months postoperatively, patients with n or minimal degenerative changes showed a significant improvement in pain and severity whereas no difference was found in those with moderate or severe changes. CONCLUSIONS: Patients with spasmodic torticollis have an increased risk of developing premature degenerative changes of the upper cervical spine that tend to be on the side towards which the head is turned or tilted and compromise outcome after surgery. Effective early treatment of spasmodic torticollis with botulinum toxin seems to have a protective effect. Patients with spasmodic torticollis and restricted head mobility who do not adequately respond to treatment should undergo imaging of the upper cervical spine. Patients with imaging evidence of moderate or severe degenerative changes seem to respond poorly to selective peripheral denervation.

Adult↗
PubMed2000

Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group.

OBJECTIVE: To evaluate whether visual assessment of [123I]-FP-CIT (DaTSCAN, Nycomed Amersham, plc) single photon emission computerized tomography (SPECT) images can differentiate between parkinsonism and essential tremor (ET). METHODS: [123I]-FP-CIT SPECT imaging was conducted in a six-center study of 158 patients with a clinical diagnosis of parkinsonism compared with 27 ET cases and 35 healthy volunteers. Striatal uptake of the radioligand was graded normal or abnormal, and abnormal images were further graded to three levels of severity. An institutional read whereby each center visually assessed the images blinded to the clinical data and a consensus blinded read by a panel of five was undertaken. RESULTS: The institutional reading scored 154 of 158 cases of parkinsonism abnormal, all 27 cases of ET as normal, and 34 of 35 healthy volunteers as normal compared with the consensus blinded read scoring 150 cases of parkinsonism as abnormal, 25 ET cases as normal, and 33 healthy volunteers as normal. Sensitivity for the clinical diagnosis of parkinsonism was 97% and specificity for ET was 100% for the institutional read, whereas sensitivity was 95% and specificity 93% for the consensus blinded read. Semiquantitative analysis of specific: nonspecific caudate and putamen uptake were consistent with the results of visual inspection. CONCLUSION: Visual assessment of [123I]-FP-CIT SPECT images is an easily applied diagnostic test which is helpful in the differential diagnosis of tremor disorders and in confirming a clinical diagnosis of a hypokinetic-rigid syndrome.

Adult↗
PubMed1999

Striatal dopaminergic function in restless legs syndrome: 18F-dopa and 11C-raclopride PET studies.

OBJECTIVE: To use PET to study striatal dopaminergic function in restless legs syndrome (RLS). BACKGROUND: RLS is a common disorder experienced by as much as 5% of the population. It has been suggested that this condition is associated with a disturbance of dopaminergic transmission. METHODS: The authors measured nigrostriatal terminal dopamine storage with 18F-dopa and striatal D2 receptor binding with 11C-raclopride PET in 13 RLS patients, five of whom were receiving treatment with L-dopa at the time of scanning. RLS results were compared with those of age-matched control subjects. RESULTS: Mean caudate and putamen 18F-dopa uptake were mildly reduced in the RLS patients compared with control subjects, and this reached significance (p = 0.04) in the putamen. Mean D2 binding was reduced in the caudate (p = 0.01) and the putamen (p = 0.008) in RLS patients compared with control subjects. Six of the 13 RLS patients had caudate and putamen D2 binding reduced below the control range. Three other RLS patients showed only reduced putamen D2 binding. There were no significant differences in striatal 18F-dopa uptake or D2 binding between L-dopa-naive and L-dopa-treated RLS patients. CONCLUSIONS: These PET findings support the hypothesis of central dopaminergic dysfunction in RLS.

Aged↗
PubMed1999

Selegiline-induced postural hypotension in Parkinson's disease: a longitudinal study on the effects of drug withdrawal.

OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.

Aged↗
PubMed1999

GPi firing rate modification during beginning-of-dose motor deterioration following acute administration of apomorphine.

We present a patient with clinically evident beginning-of-dose motor deterioration who had undergone posteroventral pallidotomy. This patient underwent an intrasurgical apomorphine test followed by single cell recording of the internal globus pallidus (GPi) to determine changes in GPi firing rate during the occurrence of such phenomenon. A significant increase in GPi firing rate coincident with worsening of patient disabilities prior to improvement was found. This finding suggests that beginning-of-dose motor deterioration may be mediated by enhanced thalamic inhibition.

Action Potentials↗
PubMed1999

Neurofibrillary tangle parkinsonian disorders--tau pathology and tau genetics.

A number of related conditions, including progressive supranuclear palsy (PSP), corticobasal degeneration, Pick's disease, and the parkinsonism dementia complex of Guam, are characterized by the deposition of tau neurofibrillary tangles in the absence of amyloid pathology. These diseases share some overlap in their topography and clinical features but can be subdivided into three main groups according to the isoforms of the alternatively spliced tau gene that are deposited. The recent description of mutation in tau in frontotemporal dementia, and a common variant of tau that predisposes to PSP, and the relationship of these changes to the tau protein subgroups offers new insights into the pathogenesis of these disorders.

Brain↗