Showing papers in "Journal of Neurology, Neurosurgery, and Psychiatry in 1994"

Myogenic potentials generated by a click-evoked vestibulocollic reflex.

Abstract: Electromyograms (EMGs) were recorded from surface electrodes over the sternomastoid muscles and averaged in response to brief (0.1 ms) clicks played through headphones. In normal subjects, clicks 85 to 100 dB above our reference (45 dB SPL: close to perceptual threshold for normal subjects for such clicks) evoked reproducible changes in the averaged EMG beginning at a mean latency of 8.2 ms. The earliest potential change, a biphasic positive-negativity (p13-n23), occurred in all subjects and the response recorded from over the muscle on each side was predominantly generated by afferents originating from the ipsilateral ear. Later potentials (n34, p44), present in most but not all subjects, were generated bilaterally after unilateral ear stimulation. The amplitude of the averaged responses increased in direct proportion to the mean level of tonic muscle activation during the recording period. The p13-n23 response was abolished in patients who had undergone selective section of the vestibular nerve but was preserved in subjects with severe sensorineural hearing loss. It is proposed that the p13-n23 response is generated by activation of vestibular afferents, possibly those arising from the saccule, and transmitted via a rapidly conducting oligosynaptic pathway to anterior neck muscles. Conversely, the n34 and p44 potentials do not depend on the integrity of the vestibular nerve and probably originate from cochlear afferents.

Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage.

Abstract: A group of patients with damage to the ventral part of the frontal lobes was severely impaired relative to a group of patients without damage in this area (the non-ventral group) in the reversal and in the extinction of simple visual discrimination tests. In these tests they continued to make responses to a previously rewarded stimulus. Patients often reported verbally that the contingencies had changed, but were unable to alter their behaviour appropriately. These impairments occurred independently of IQ or verbal memory impairments. The perseverative touching of a previously rewarded stimulus is consistent with work with non-human primates showing impaired reversal and extinction after orbitofrontal lesions. Performance on these reversal and extinction tests was highly correlated with scores obtained on a behaviour questionnaire, which reflected the degree of disinhibited and socially inappropriate behaviour exhibited by patients. It is suggested that a difficulty in modifying responses, especially when followed by negative consequences, as manifested in these simple laboratory tests, may contribute to the inappropriate behaviour shown in daily life by patients with frontal lobe damage.

Cognitive impairment after stroke: frequency, patterns, and relationship to functional abilities.

Abstract: Cognitive function was examined in 227 patients three months after admission to hospital for ischaemic stroke, and in 240 stroke-free controls, using 17 scored items that assessed memory, orientation, verbal skills, visuospatial ability, abstract reasoning, and attentional skills. After adjusting for demographic factors with standardised residual scores in all subjects, the fifth percentile was used for controls as the criterion for failure on each item. The mean (SD) number of failed items was 3.4 (3.6) for patients with stroke and 0.8 (1.3) for controls (p 40). It is concluded that cognitive impairment occurs frequently after stroke, commonly involving memory, orientation, language, and attention. The presence of cognitive impairment in patients with strike has important functional consequences, independent of the effects of physical impairment. Studies of stroke outcome and intervention should take into account both cognitive and physical impairments.

Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report.

Abstract: The Committee of the European Concerted Action for Multiple Sclerosis (Charcot Foundation) organised five workshops to discuss CSF analytical standards in the diagnosis of multiple sclerosis. This consensus report from 12 European countries summarises the results of those workshops. It is hoped that neurologists will confer with their colleagues in clinical chemistry to arrange the best possible local practice. The most sensitive method for the detection of oligoclonal immunoglobulin bands is isoelectric focusing. The same amounts of IgG in parallel CSF and serum samples are used and oligoclonal bands are revealed with IgG specific antibody staining. All laboratories performing isoelectric focusing should check their technique at least annually using "blind" standards for the five different CSF and serum patterns. Quantitative measurements of IgG production in the CNS are less sensitive than isoelectric focusing. The preferred method for detection of blood-CSF barrier dysfunction is the albumin quotient. The CSF albumin or total protein concentrations are less satisfactory. These results must be interpreted with reference to the age of the patient and the local method of determination. Cells should be counted. The normal value is no more than 4 cells/microliters. Among evolving optional tests, measurement of the combined local synthesis of antibodies against measles, rubella, and/or varicella zoster could represent a significant advance if it offers higher specificity (not sensitivity) for identifying chronic rather than acute inflammation. Other tests that may have useful correlations with clinical indices include those for oligoclonal free light chains, IgM, IgA, or myelin basic protein concentrations.

Beta amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer's disease.

Abstract: In a recent preliminary study it was reported that a severe head injury resulted in the deposition of beta amyloid protein (beta AP) in the cortical ribbon of 30% of patients who survived for less than two weeks. Multiple cortical areas have now been examined from 152 patients (age range 8 weeks-81 years) after a severe head injury with a survival time of between four hours and 2.5 years. This series was compared with a group of 44 neurologically normal controls (age range 51 to 80 years). Immunostaining with an antibody to beta AP confirmed the original findings that 30% of cases of head injury have beta AP deposits in one or more cortical areas. Increasing age seemed to accentuate the extent of beta AP deposition and potential correlations with other pathological changes associated with head injury were also investigated. In addition, beta amyloid precursor protein (beta APP) immunoreactivity was increased in the perikarya of neurons in the vicinity of beta AP deposits. The data from this study support proposals that increased expression of beta APP is part of an acute phase response to neuronal injury in the human brain, that extensive overexpression of beta APP can lead to deposition of beta AP and the initiation of an Alzheimer disease-type process within days, and that head injury may be an important aetiological factor in Alzheimer's disease.

Jugular venous desaturation and outcome after head injury.

Abstract: Early experience with continuous monitoring of jugular venous oxygen saturation (SjvO2) suggested that this technology might allow early identification of global cerebral ischaemia in patients with severe head injury. The purpose of the present study was to examine the relationship between episodes of jugular venous desaturation and neurological outcome. One hundred and sixteen severely head-injured patients had continuous monitoring of SjvO2 during days 1-5 after injury. Episodes of jugular venous desaturation (SjvO2 < 50% for more than 10 minutes) were prospectively identified, and the incidence of desaturation was correlated with neurological outcome: 77 episodes of desaturation occurred in 46 of the 116 patients; 27 had one episode and 19 had multiple episodes of desaturation. The causes of these episodes were systemic (n = 36), cerebral (n = 35), or both (n = 6). Most of the episodes were less than 1 hour in duration, and it is probable that many of them would not have been detected without continuous measurement of SjvO2. Episodes of desaturation were most common on day 1 after injury, and were twice as common in patients with a reduced cerebral blood flow as in patients with a normal or elevated cerebral blood flow. The occurrence of jugular venous desaturation was strongly associated with a poor neurological outcome. The percentage of patients with a poor neurological outcome was 90% with multiple episodes of desaturation and 74% in patients with one desaturation, compared to 55% in patients with no episodes of desaturation. When adjusted for all co-variates that were found to be significant, including age, Glasgow coma score, papillary reactivity, type of injury, lowest recorded cerebral perfusion pressure, and highest recorded temperature, the incidence of desaturation remained significantly associated with a poor outcome. Although a cause and effect relationship with outcome cannot be established in this study, the data suggest that monitoring SvO2 might allow early identification and therefore treatment of many types of secondary injury to the brain.

Motor neuron disease.

Abstract: For neurologists, the management of motor neuron disease (MND) involves prompt and accurate diagnosis; an understanding of natural history, prognosis, and of the physical and psychological consequences of the disease for the individual and for carers; familiarity with the techniques, philosophies, and ethical aspects of symptomatic treatment, rehabilitation medicine and palliative care; and awareness of the new opportunities for research into the causes and treatment of MND and other motor neuron disorders. Because MND is a relatively rare condition for most health workers, the neurologist can make an important contribution to effective multidisciplinary management. Underprovision of neurology services militates against this in the United Kingdom. Nevertheless, an argument can be made that MND be treated as a \"special case\" and that health districts should develop appropriate models of interdisciplinary care, not necessarily led, but advised and supported by, local neurologists.

Ability to modulate walking cadence remains intact in Parkinson's disease.

Abstract: Gait hypokinesia (slowness) is a characteristic feature of Parkinson's disease. It is not clear, however, whether the slowness is due to a problem in regulation of the timing of consecutive steps or the control of stride size. Examination of cadence control for slow to medium walking speeds has shown an increase in step frequency that was a compensation for reduced stride length. In this investigation the ability of Parkinsonian patients to modulate their cadence (steps per minute) at the fast walking speeds exhibited by age and height matched controls was examined. The findings indicated that cadence control remains unaffected throughout its entire range in Parkinson's disease and that gait hypokinesia is directly attributable to an inability to internally generate sufficiently large steps.

Cerebral responses to pain in patients with atypical facial pain measured by positron emission tomography.

Abstract: The localised PET cerebral correlates of the painful experience in the normal human brain have previously been demonstrated. This study examined whether these responses are different in patients with chronic atypical facial pain. The regional cerebral responses to non-painful and painful thermal stimuli in six female patients with atypical facial pain and six matched female controls were studied by taking serial measurements of regional blood flow by PET. Both groups displayed highly significant differences in responses to painful heat compared with non-painful heat in the thalamus, anterior cingulate cortex (area 24), lentiform nucleus, insula, and prefrontal cortex. These structures are closely related to the "medial pain system". The atypical facial pain group had increased blood flow in the anterior cingulate cortex and decreased blood flow in the prefrontal cortex. These findings show the importance of the anterior cingulate cortex and the reciprocal (possibly inhibitory) connections with the prefrontal cortex in the processing of pain in patients with this disorder. A hypothesis is proposed to explain the mechanisms of cognitive and pharmacological manipulation of these pain processes.

Intracerebral propagation of interictal activity in partial epilepsy: implications for source localisation.

Abstract: The hypothesis that focal scalp EEG and MEG interictal epileptiform activity can be modelled by single dipoles or by a limited number of dipoles was examined. The time course and spatial distribution of interictal activity recorded simultaneously by surface electrodes and by electrodes next to mesial temporal structures in 12 patients being assessed for epilepsy surgery have been studied to estimate the degree of confinement of neural activity present during interictal paroxysms, and the degree to which volume conduction and neural propagation take part in the diffusion of interictal activity. Also, intrapatient topographical correlations of ictal onset zone and deep interictal activity have been studied. Correlations between the amplitudes of deep and surface recordings, together with previous reports on the amplitude of scalp signals produced by artificially implanted dipoles suggest that the ratio of deep to surface activity recorded during interictal epileptiform activity on the scalp is around 1:2000. This implies that most such activity recorded on the scalp does not arise from volume conduction from deep structures but is generated in the underlying neocortex. Also, time delays of up to 220 ms recorded between interictal paroxysms at different recording sites show that interictal epileptiform activity can propagate neuronally within several milliseconds to relatively remote cortex. Large areas of archicortex and neocortex can then be simultaneously or sequentially active via three possible mechanisms: (1) by fast association fibres directly, (2) by fast association fibres that trigger local phenomena which in turn give rise to sharp/slow waves or spikes, and (3) propagation along the neocortex. The low ratio of deep-to-surface signal on the scalp and the simultaneous activation of large neocortical areas can yield spurious equivalent dipoles localised in deeper structures. Frequent interictal spike activities can also take place independently in areas other than the ictal onset zone and their interictal propagation to the surface is independent of their capacity to trigger seizures. It is concluded that: (1) the deep-to-surface ratios of electromagnetic fields from deep sources are extremely low on the scalp; (2) single dipoles or a limited number of dipoles are not adequate for surgical assessment; (3) the correct localisation of the onset of interictal activity does not necessarily imply the onset of seizures in the region or in the same hemisphere. It is suggested that, until volume conduction and neurophysiological propagation can be distinguished, semiempirical correlations between symptomatology, surgical outcome, and detailed presurgical modeling of the neocortical projection patterns by combined MEG, EEG, and MRI could be more fruitful than source localization with unrealistic source models.

Cognitive deficits in progressive supranuclear palsy, Parkinson's disease, and multiple system atrophy in tests sensitive to frontal lobe dysfunction.

Abstract: Groups of patients with idiopathic Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy or Steele-Richardson-Olszewski syndrome, matched for overall clinical disability, were compared using three computerised cognitive tests previously shown to be sensitive to frontal lobe dysfunction On a test of planning based on the Tower of London task, all three groups were impaired, but in different ways The groups with palsy and Parkinson's disease were slower in the measure of initial thinking time, whereas the group with multiple system atrophy was only slower in a measure of thinking time subsequent to the first move, resembling patients with frontal lobe damage On a test of spatial working memory, each group showed deficits relative to their matched control groups, but the three groups differed in their strategy for dealing with this task On a test of attentional set shifting, each group was again impaired, mainly at the extradimensional shifting stage, but the group with Steele-Richardson-Olszewski syndrome exhibited the greatest deficit The results are compared with previous findings in patients with Alzheimer's disease or frontal lobe damage It is concluded that these basal ganglia disorders share a distinctive pattern of cognitive deficits on tests of frontal lobe dysfunction, but there are differences in the exact nature of the impairments, in comparison not only with frontal lobe damage but also with one another

Initial letter and semantic category fluency in Alzheimer's disease, Huntington's disease, and progressive supranuclear palsy.

Abstract: Ten patients with dementia of Alzheimer's type, 10 patients with progressive supranuclear palsy, and 10 patients with Huntington's disease were compared on two types of verbal fluency task--namely, initial letter fluency and category (semantic) fluency. The groups were carefully matched for overall level of dementia on the dementia rating scale, and were compared with 25 age matched normal controls. The controls found letter fluency more difficult than category fluency, and this relative pattern of performance was repeated in the progressive supranuclear palsy and Huntington's disease groups, although both groups were significantly impaired on both tasks. By contrast, patients with Alzheimer's disease performed just as poorly as the progressive supranuclear palsy and Huntington's disease groups on the category tasks, but were significantly less impaired at letter fluency, performing at near normal levels on this task. From these results, it is suggested that the performances of patients with progressive supranuclear palsy and Huntington's disease relate largely to initiation and retrieval problems secondary to disruption of frontostriatal circuits, whereas in Alzheimer's disease, the poorer performance on category fluency is due principally to the breakdown of semantic knowledge, which probably reflects temporal neocortical involvement.

Relation of anosognosia to frontal lobe dysfunction in Alzheimer's disease.

Abstract: A self-rating scale of memory functions was administered to 24 non-depressed patients with probable Alzheimer's disease, divided into two groups according to the overall severity of dementia (mild, mini-mental state (MMS) > 21; moderate, MMS between 10 and 20). These groups did not significantly differ in their self-rating of memory functions. The same questionnaire was submitted to a member of each patient's family, who had to rate the patient's memory. An "anosognosia score" was defined as the difference between patient's and family's ratings. This score was highly variable, and covered, in the two groups, the full range between complete awareness of deficits and total anosognosia. Correlations between the anosognosia score and several neuropsychological data were searched for. No significant correlation was found with either the Wechsler memory scale, the MMS, or linguistic abilities and gestures. In contrast, this score was highly correlated with the "frontal score", defined as the sum of scores on the Wisconsin card sorting test (WCST), verbal fluency, Luria's graphic series, and "frontal behaviours" (prehension, utilisation, imitation behaviours, inertia, indifference). Among these tests of executive functions, the highest correlation with the anosognosia score was obtained on the WCST. This suggests that anosognosia in Alzheimer's disease is not related to the degree of cognitive deterioration but results, at least in part, from frontal dysfunction.

Pathophysiology of spasticity.

Abstract: Spasticity is a frequent and often disabling feature of neurological disease. It may result in loss of mobility and pain from spasms. The core feature of the spastic state is the exaggeration of stretch reflexes, manifest as hypertonus. The stretch reflex threshold is reduced,' and its gain may be increased.2 The result is the velocity-dependent increase in resistance of a passively stretched muscle or muscle group detected clinically. Often, this is associated with a sudden melting of resistance during stretch, the clasp-knife phenomenon. In addition, there may be other related signs, such as weakness, impairment of fine movements of the digits, hyperreflexia, loss of cutaneous reflexes, Babinski's sign, clonus, spasms and changes in posture. Spasticity is traditionally ascribed to damage to the pyramidal tract. Work, however, particularly in animals, clearly implicates additional motor tracts in the pathophysiology of the spastic syndrome. The present editorial draws together old and new observations to provide a working hypothesis explaining the pathophysiology of spastic hypertonus, and some of the related elements of the human spastic syndrome. Possible changes in spinal neuronal circuitry have been the focus of several recent reviews34 and will not be discussed.

Gangliogliomas: clinical, radiological, and histopathological findings in 51 patients.

Abstract: Clinical, radiological, and histopathological features of 51 surgically treated gangliogliomas were evaluated retrospectively. The most common presenting symptoms were epileptic seizures (47 patients (92%)). Focal neurological deficits occurred in 8% of the patients. The duration of symptoms at the time of operation ranged from three months to 45 years, mean 11 years. The temporal lobe was affected in 43 patients (84%), the frontal lobe in five patients (10%), and the occipital lobe in one patient (2%). Two of the tumours (4%) were localised infratentorially. On MRI, solid tumour parts usually showed a pronounced signal increase on proton density images and a less pronounced signal increase on T2 weighted images, whereas solid components were mainly isointense on T1 weighted images. Contrast enhancement was noted in 16 of 36 patients (44%). Cystic tumour parts were found in 23 of 40 patients (57%), all characterised by signal increase on T2 weighted images and decreased T1 signals. Signal deviation of cystic tumour parts on proton density images was variable. Computed tomography was performed in 17 patients and showed hypodense lesions in 10 (59%), and calcifications in seven (41%) cases. Surgery included complete tumour removal in 44 patients (86%) and partial resection in seven (14%). In six patients (12%) there were transient postoperative complications. One patient (2%) died postoperatively due to pulmonary embolism. Histopathological examination of the surgical specimens showed low grade gangliogliomas in 49 cases (96%) and anaplastic gangliogliomas in two (4%). Control MRI of 31 patients with a mean follow up period of 16 months was uneventful in all but one case of an anaplastic ganglioglioma. In all patients in whom the ganglioglioma was associated with medically intractable seizures the operation resulted in complete relief of seizures or a noticeable improvement of the epilepsy.

Multiple system atrophy: natural history, MRI morphology, and dopamine receptor imaging with 123IBZM-SPECT.

Abstract: Sixteen patients with a clinical diagnosis of probable multiple system atrophy (MSA) were examined clinically by MRI and by 123I-iodobenzamide single photon emission computed tomography (IBZM-SPECT). The clinical records of another 16 patients were also analysed retrospectively. On the basis of their clinical presentation, patients were subdivided into those with prominent parkinsonism (MSA-P, n = 11) and those with prominent cerebellar ataxia (MSA-C, n = 21). Autonomic symptoms were present in all patients and preceded the onset of motor symptoms in 63% of patients. Calculated median lifetime and the median time to become wheelchair bound after onset of disease were significantly shorter for MSA-P than for MSA-C (lifetime: 4.0 v 9.1 years; wheelchair: 3.1 vs 5.0 years) suggesting a better prognosis for cerebellar patients. A significant loss of striatal dopamine receptors (below 2 SD threshold) was detected by IBZM-SPECT in 63% of the patients (56% below 2.5 SD threshold). There was no difference between patients with MSA-C and those with MSA-P in the proportion with significant receptor loss and the extent of dopamine receptor loss. Planimetric MRI evaluation showed cerebellar and brainstem atrophy in both groups. Atrophy was more pronounced in patients with MSA-C than in those with MSA-P. Pontocerebellar hyperintensities and putaminal hypointensities on T2 weighted MRI were found in both groups. Pontocerebellar signal abnormalities were more pronounced in MSA-C than in MSA-P, whereas the rating scores for area but not for intensity of putaminal abnormalities were higher in MSA-P. MRI and IBZM-SPECT provide in vivo evidence for combined basal ganglia and pontocerebellar involvement in almost all patients in this series.

Third occipital nerve headache: a prevalence study.

Abstract: A consecutive series of 100 patients was studied to determine the prevalence of third occipital nerve headache in patients with chronic neck pain (> three months in duration) after whiplash. Seventy one patients complained of headache associated with their neck pain. Headache was the dominant complaint of 40 patients, but was only a secondary problem for the other 31. Each patient with headache underwent double blind, controlled diagnostic blocks of the third occipital nerve. On two separate occasions the nerve was blocked with either lignocaine or bupivacaine, in random order. The diagnosis of third occipital nerve headache was made only if both blocks completely relieved the patient's upper neck pain and headache and the relief lasted longer with bupivacaine. The prevalence of third occipital nerve headache among all 100 whiplash patients was 27% (95% confidence interval (95% CI) 18-36%) and among those with dominant headache the prevalence was as high as 53% (95% CI 37-68%). There were no distinguishing features on history or examination that enabled a definitive diagnosis to be made before the nerve blocks. Those patients with a positive diagnosis, however, were significantly more likely to be tender over the C2-3 zygapophysial joint (p = 0.01). Third occipital nerve headache is a common condition in patients with chronic neck pain and headache after whiplash. Third occipital nerve blocks are essential to make this diagnosis.

Herpes simplex encephalitis: long term magnetic resonance imaging and neuropsychological profile.

Abstract: The first comprehensive in vivo documentation of the long term profile of pathological and spared tissue is described in a group of 10 patients with a diagnosis of herpes simplex encephalitis, who were left with memory difficulties as a major residual sequel of their condition. With a dedicated MRI protocol, which included high resolution images of temporal lobe and limbic system areas, data are provided on structures that have recently gained importance as anatomical substrates for amnesia. The major features of the lesion profile were: (1) unilateral or bilateral hippocampal damage never occurred in isolation, and was often accompanied by damage to the parahippocampus, the amygdala, specific temporal lobe gyri, and the temporal poles; (2) the insula was always abnormal; (3) neocortical temporal lobe damage was usually unilateral or asymmetric. It never occurred in isolation, and was invariably associated with more medial pathological changes; (4) anterior and inferior temporal lobe gyri were damaged more often and more severely than posterior and superior temporal lobe gyri; (5) pronounced abnormality was often present in the substantia innominata (region of the basal forebrain/anterior perforated substance); (6) there was evidence of significant abnormality in the fornix; (7) there was evidence of damage to the mammillary bodies; (8) thalamic nuclei were affected in around 50% of cases, with damage usually unilateral; (9) frontal lobe damage was present in a few patients, and affected medial areas more than dorsolateral areas; (10) there was some involvement of the striatum, although this was usually unilateral and mild; (11) there was usually limited involvement of the cingulate gyrus and of the parietal and occipital lobes; (12) the cerebellum and brain stem were never damaged. Lesion covariance analysis indicated a close relation between the presence of abnormalities in temporal lobe and limbic-diencephalic regions. Unlike severe head injury, lesions in the temporal pole were not associated with the presence of lesions in the orbitofrontal cortex. Long term neuropsychological impairments were characterised by a dense amnesia in 60% of cases, and a less serve but noticeable anterograde memory impairment in the others. Naming and problem solving deficits were found in a small number of cases. Only two patients were able to return to open employment. Severity of amnesia showed a significant relation with severity of damage to medical limbic system structures such as the hippocampus, with bilateral damage being particularly important. By contrast, there was a minimal relation between memory loss and severity of damage to the thalamus, to lateral temporal lobe areas, or to the frontal lobes.

Intravesical capsaicin for treatment of detrusor hyperreflexia.

Abstract: An intravesical instillation of 100 ml 1 or 2 mmol/l capsaicin has been used to treat detrusor hyperreflexia giving rise to intractable urinary incontinence in 12 patients with spinal cord disease and two other patients with detrusor overactivity of non-spinal origin. Nine patients, all of whom had spinal cord disease, showed some improvement in bladder function. The benefit was only shortlived and partial in four, but the remaining five achieved complete continence while performing intermittent self catheterisation. Urodynamic studies in these nine patients showed an increase in mean (SD) bladder capacity from 106 (57) to 302 (212) ml and a fall in the maximum detrusor pressure from 54 (20) to 36 (10) cm of water. There were no short term ill effects from the instillation and the improvement in bladder function lasted for between three weeks to six months, when in some patients it was repeated. The improvement in bladder behaviour shown in this study can be interpreted as showing that capsaicin sensitive afferents play an important part in the pathogenesis of detrusor hyperreflexia in spinal humans. Intravesical capsaicin seems a promising means of treating intractable detrusor hyperreflexia and studies with this substance may shed new light on other disorders of detrusor activity that cause incontinence.

A randomised controlled study comparing bromocriptine to which levodopa was later added, with levodopa alone in previously untreated patients with Parkinson's disease: a five year follow up.

Abstract: This pilot study was performed to compare the occurrence of long term motor complications in Parkinson's disease when the introduction of levodopa was delayed by an initial treatment with high doses of bromocriptine alone. The trial was a prospective randomised controlled study comparing 31 previously untreated patients with Parkinson's disease initially given bromocriptine alone to which levodopa was later added (group B/D) and 29 other previously untreated patients with Parkinson's disease immediately given levodopa alone (group D). The end point was the occurrence of the first motor complications (wearing off or dyskinesia). Group B/D patients received bromocriptine (52 (SEM 5) mg/day) for 2.7 years, to which levodopa was later added (471 (SEM 46) mg/day). Group D patients received a comparable dose of levodopa alone (569 (SEM 47) mg/day). Both had similar disability scores at the end of the study. Motor complications were fewer and appeared later in group B/D than in group D (56% after 4.9 (SEM 0.5) years of treatment v 90% after 2.7 (SEM 0.5) years, p < 0.01). Wearing off appeared later (p < 0.01) in group B/D (4.5 (SEM 0.6) years) than in group D (2.9 (SEM 0.6) years). Peak dose dyskinesia occurred less often in group B/D patients (three v 14 cases, p < 0.01). This study showed that a three year initial monotherapy with high doses of bromocriptine followed by addition of levodopa delayed the occurrence of long term motor complications usually found in patients with Parkinson's disease treated with levodopa alone from the beginning.

Anatomical correlates of visual and tactile extinction in humans: a clinical CT scan study.

Abstract: The anatomical correlates of tactile and visual extinction with double simultaneous stimulation were investigated in a series of 159 patients with right brain damage caused by stroke. Forty six patients showed extinction (22 tactile, 14 visual, 10 tactile and visual). Over 50% of the patients with extinction had deep lesions, which were found in about 25% of the patients with visuospatial neglect not associated with extinction. In the patients with extinction and cortico-subcortical damage the paraventricular occipital white matter and the dorsolateral frontal cortex were most often involved. By contrast, when neglect was also present, the lesions clustered in the inferior parietal lobule. These data suggest, from an anatomical perspective, that partly different neural mechanisms may underlie neglect and extinction. The comparatively high frequency of subcortical lesions involving the ascending pathways may be a neural correlate of a sensory component of extinction.

Pure motor demyelinating neuropathy: deterioration after steroid treatment and improvement with intravenous immunoglobulin.

Abstract: Within one month of starting oral prednisolone treatment weakness unexpectedly increased in four patients aged 34 to 75 years with purely motor forms of acquired chronic demyelinating neuropathy. By contrast, steroids produced the expected improvement in 11 other patients with symmetric sensorimotor chronic inflammatory demyelinating polyneuropathy. Two of the patients with purely motor demyelinating neuropathy were subsequently treated with high dose IVIg (0.4 g/kg/day for five days) with prompt improvements in strength measurements and motor nerve conduction. Thus IVIg seems to be the treatment of choice and steroids should be used with extreme caution, if at all, in patients with purely motor forms of acquired demyelinating polyneuropathy.

A central executive deficit in patients with Parkinson's disease.

Abstract: Eight patients with Parkinson's disease and eight matched controls were tested for concurrent task performance to examine whether Parkinson's disease produces deficits in the coordinating and integrating function of the central executive component of Baddeley's working memory model. Consistent with this prediction, the patients showed a significant decline in performance on a random pursuit tracking task while recalling digit span forward sequences, whereas the controls showed no such change. Performance on the component pursuit and digit span tasks, which did not differ between groups, was equated across subjects by varying the size of a target square and by using individual subjects' digit spans. The patient group also produced poorer word fluency scores and reported higher levels of depression, but there was no significant impairment on the Wisconsin card sort test. There was no association between dual task performance and any psychometric measure, target size, or disease related variables. Baddeley's working memory model is advantageous in providing a rich conceptual basis to explore and characterise cognitive abilities in patients with Parkinson's disease.

Differential diagnosis of Parkinson's disease, multiple system atrophy, and Steele-Richardson-Olszewski syndrome: discriminant analysis of striatal 18F-dopa PET data.

Abstract: Clinicopathological series indicate that the clinical diagnosis of Parkinson's disease is correct in only 80% of cases. Multiple system atrophy (MSA) and Steele-Richardson-Olszewski syndrome (SRO) comprise most of the misdiagnoses. By means of 18F-dopa PET the pattern of nigrostriatal dopaminergic dysfunction in 28 patients with clinically probable Parkinson's disease, 25 with MSA, and 10 patients with SRO, was assessed and compared with the pattern in 27 normal subjects. Discriminant function analysis was used to assess the ability of 18F-dopa PET to categorize individual parkinsonian patients on the basis of their caudate and putamen tracer uptake. Discriminant function analysis assigned all control subjects a normal category. One Parkinsonian patient out of 63 was classified as "normal" on the basis of PET findings, although this patient had significantly reduced putamen 18F-dopa uptake. Discriminant function analysis was less effective at distinguishing different categories of akinetic-rigid syndrome on the basis of their striatal 18F-dopa uptake, as judged against clinical criteria. Patients clinically labelled as having typical or atypical Parkinsonian syndromes were assigned the same category on PET criteria 64% and 69% of the time, respectively. When all three categories of Parkinson's disease, MSA, and SRO were considered together, clinical and 18F-dopa PET findings correlated in 64% of patients assigned a diagnosis of Parkinson's disease and 70% of those given a diagnosis of SRO; MSA was less readily discriminated, patients with MSA being assigned to MSA, Parkinson's disease, and SRO groups with equal frequency. The correlation between clinical and discriminant function analysis assignment improved when separate comparisons were made between Parkinson's disease and MSA, or Parkinson's disease and SRO groups. In these analyses, clinical and PET categorisation of MSA and Parkinson's disease agreed in 60% of cases, and of SRO and Parkinson's disease in 90% of cases. In summary, (18)F-dopa PET successfully discriminates normal subjects from parkinsonian patients, and patients with Parkinson's disease from patients with SRO, but is less reliable in distinguishing Parkinson's disease from MSA. The concomitant assessment of striatal neuronal function with additional PET tracers may be necessary to reliably differentiate typical and atypical parkinsonian syndromes.

A multicentre comparative trial of sodium valproate and carbamazepine in adult onset epilepsy. Adult EPITEG Collaborative Group.

Abstract: The long-term efficacy and safety of sodium valproate and carbamazepine in adult outpatients with newly diagnosed primary generalised or partial and secondarily generalised seizures were compared in a randomised, open, multicentre study at 22 neurology outpatient clinics. Patients were randomised to oral sodium valproate (Epilim EC enteric coated 200 mg tablets twice daily, n = 149) or oral carbamazepine (100 mg twice daily increasing to 200 mg twice daily in week 2, n = 151) and followed up for three years. If clinically necessary, dosages were regularly increased until seizures were controlled or toxicity developed. Sodium valproate and carbamazepine controlled both primary generalised and partial seizures equally effectively overall. Significantly more patients on sodium valproate than carbamazepine (126/140 (90%) v 105/141 (75%), p = 0.001) remained on randomised treatment for at least six months. Skin rashes occurred significantly more often in carbamazepine recipients than in sodium valproate recipients (11.2% v 1.7%, p < 0.05) and carbamazepine was associated with a higher withdrawal rate because of adverse events (15% v 5% on sodium valproate) in the first six months of treatment. There was no difference between the drugs in the rate of withdrawal because of poor seizure control at any stage, regardless of seizure type. At the end of the three year trial period, over 70% of the available patients were still on randomised treatment or had recently stopped treatment after achieving full seizure control. Sodium valproate and carbamazepine were both associated with a high degree of overall seizure control regardless of seizure type and both have good long-term tolerability in adult patients with newly diagnosed epilepsy. Recommendations are made for a higher initial dosage regime for sodium valproate in partial seizures.

Spectrum of primary intracerebral haemorrhage in Perth, Western Australia, 1989-90: incidence and outcome.

Abstract: In a population based register of stroke (n = 536) compiled in Perth, Western Australia during an 18 month period in 1989-90, 60 cases (11%) of primary intracerebral haemorrhage were identified among 56 persons (52% men). The mean age of these patients was 68 (range 23-93) and 46 (77%) events were first ever strokes. The crude annual incidence was 35 per 100,000, with a peak in the eighth decade, and a male predominance. Deep and lobar haemorrhages each accounted for almost one third of all cases. The clinical presentations included sudden coma (12%), headache (8%), seizures (8%), and pure sensory-motor stroke (3%). Primary intracerebral haemorrhage was the first presentation of leukaemia in two cases (both fatal) and it followed an alcoholic binge in four cases. 55% had a history of hypertension. 16 (27%) patients, half of whom had a history of hypertension, were taking antiplatelet agents, and one patient was taking warfarin. There were only two confirmed cases of amyloid angiopathy. The overall 28 day case fatality was 35%, but this varied from 100% for haemorrhages in the brainstem to 22% for those in the basal ganglionic or thalamic region. Other predictors of early death were intraventricular extension of blood, volume of haematoma, mass effect, and coma and severe paresis at onset. Although based on small numbers, these data confirm the heterogeneous nature of primary intracerebral haemorrhage, but they also suggest a different clinical spectrum of this type of stroke in the community compared with the experience of specialist neurological units.

A neuropsychological instrument adding to the description of patients with suspected cortical dementia: the Milan overall dementia assessment.

Abstract: A new, short, neuropsychologically oriented test for dementia assessment--the Milan Overall Dementia Assessment (MODA)--is described. Age and education adjusted norms based on 217 healthy controls are given. A validation study on 312 outpatients suspected of dementia (121 with probable Alzheimer's disease) showed that the MODA differentiated patients with cognitive impairment from normal subjects more effectively than did the DSM III-R. The correlation between the MODA and the mini mental state examination was 0.63 in controls and 0.84 in patients with Alzheimer's dementia. The MODA test-retest reliability was 0.83. The test proved to be well suited to longitudinal studies.

The Sydney Multicentre Study of Parkinson's disease: a randomised, prospective five year study comparing low dose bromocriptine with low dose levodopa-carbidopa.

Abstract: 149 previously untreated patients with Parkinson's disease were recruited over a three year period and randomly allocated to either low dose levodopa-carbidopa (< or = 600/150 mg/day) or low dose bromocriptine (< or = 30 mg/day). A five year follow up is reported on the 126 patients who completed the dose titration and who have not developed features of atypical Parkinsonism. Levodopa-carbidopa in low dosage adequately controlled symptoms in most patients and delayed the appearance of dyskinesia and end of dose failure for about two years longer than conventional doses. Only a few patients could be managed for more than one year on low dose bromocriptine alone; these patients had mild disease and asymmetric signs. Patients randomised to bromocriptine did not develop dyskinesia or troublesome end of dose failure until levodopa-carbidopa was added. The prevalence of dyskinesia in this group was lower than in patients given levodopa-carbidopa alone. The prevalence of end of dose failure was similar in the two randomisation groups once levodopa was introduced.

Handicap one year after a stroke: validity of a new scale.

Abstract: The aim was to determine the handicap experienced by subjects one year after a stroke, and assess the acceptability, validity, and reliability of a new handicap measurement scale. A cross sectional survey of 141 survivors of a cohort of consecutive hospital admissions with acute stroke was undertaken. The London handicap scale (a new health outcome measurement scale), Barthel index, Nottingham extended activities of daily living scale, Nottingham health profile, Geriatric depression score, and a global life satisfaction scale were used. 94 subjects (67%) responded to a single mailing; 89 (95%) responses were usable. Mean handicap was 0.40 (range 0.06-1.0, SD 0.20) on a scale of 0 (maximum handicap) to 1 (no handicap). All handicap dimensions showed a wide range of problems, with physical independence and occupation particularly affected. Correlations between handicap score and other outcome measures were all in the expected direction and of about the strength expected (0.36 < r < 0.69). The reliability coefficient was 0.91, limits of agreement +/- 0.19. The measurements demonstrated substantial handicap one year after a stroke, reflecting considerable unmet rehabilitation needs. The scale proved acceptable to subjects, and the results were consistent with good validity.