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

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.

Reliability of the Columbia scale for assessing signs of Parkinson's disease.

Inter- and intrarater reliability in scoring the signs of Parkinson's disease using the original Columbia scale and a modified version of this, the Sydney scale, were assessed in five neurologists participating in a long-term study of Parkinson's disease. Scoring was done on video recordings of 41 patients whose disability ranged from mild to severe. Although all the neurologists were familiar with the scales and had received training designed to produce uniformity of scoring, interrater reliability was poor. The mean score for the Columbia scale varied from 18.6 to 30 and for the Sydney scale from 15.2 to 23.2. By contrast, intrarater reliability was good. This study highlights the limitations of clinical rating scales in Parkinson's disease when more than one rater is used. In designing clinical trials, every effort should be made to ensure that the same patient is always assessed by the same rater.

The neuropsychology of de novo patients with idiopathic Parkinson's disease: the effects of age of onset.

One hundred de novo patients with Parkinson's disease (PD) were classified into two groups according to age of onset of symptoms. Seventy two patients were under 70 years and 28 were 70 years and over. All patients were given neurological and neuropsychological assessments, and the severity of the signs was rated on a modified Columbia scale. The neuropsychological assessment was also administered to 50 age-and-education-matched controls. The neuropsychological test battery included tests of verbal learning, visual memory, verbal fluency, visuospatial skill, simple and choice reaction time, language and maze learning. The late-onset patients had significant impairment in nonverbal reasoning, auditory verbal learning, visual memory and choice reaction time in contrast to early-onset patients and controls. A relationship was found between bradykinesia and widespread cognitive impairment. Severity of tremor was found to be significantly correlated with impairment in auditory verbal learning, visual memory and increased choice reaction time, while rigidity was found to be associated with cognitive impairment in verbal fluency and visuospatial skill. Using DSM II criteria, 39% of the late-onset and 8% of the early-onset group were classified as demented. Dementia was more common in patients with bilateral symmetrical disease and in those patients with marked tremor and bradykinesia. The pattern of cognitive impairment in PD was consistent with that associated with a subcortical dementia. This study confirms that the expression of PD is markedly influenced by the age of onset.

The Sydney Multicentre Study of Parkinson's disease: a report on the first 3 years.

One hundred and twenty nine de novo patients with idiopathic Parkinson's disease are being followed over a 5 year period in a double-blind multicentre study comparing low-dose bromocriptine (less than 30 mg/day) with low-dose levodopa-carbidopa (less than 600/150 mg/day). Sixty six patients have been randomised to bromocriptine and 63 patients to levodopa-carbidopa. Improvement has been greater in the levodopa-carbidopa group than in the bromocriptine group. Involuntary movements have so far only occurred in patients on levodopa-carbidopa, the incidence being much lower than is usually described with conventional doses. Mild, end-of-dose failure has occurred in both treatment groups; however, no patient has developed the "on-off" phenomenon. Low-dose levodopa-carbidopa appears to be a more effective anti-Parkinsonian treatment than low-dose bromocriptine but more prone to cause dyskinesia.

The Sydney multicentre study of Parkinson's disease. The first 18 months.

Low-dose bromocriptine therapy and low-dose levodopa-carbidopa therapy are being compared in a double-blind study over a five-year period as treatment for newly-diagnosed patients with Parkinson's disease. Ninety-four patients had entered the study by January 1986 and of these, 50 had been followed for six months or more. Preliminary results confirm that many patients with Parkinson's disease can be managed satisfactorily in the early stages of the disease with low-dose therapy. Three patients, all of whom were receiving levodopa-carbidopa therapy, developed dyskinesia. Twelve patients who had received bromocriptine had an inadequate response or developed confusion or postural hypotension. Of these patients, six had a poor response to subsequent levodopa-carbidopa therapy. While the initial improvement that results from low-dose bromocriptine therapy and low-dose levodopa-carbidopa therapy is less than one would expect with conventional doses of these agents, it is hoped that this approach will reduce the incidence of long-term side-effects such as dyskinesia and fluctuations.

Symbol production and the formulation of speech.

Symbols integrate cortical modular activity into constantly meaningful yet dissolving patterns. Symbolism is posited as one of the keys to an understanding of neurophysiological processes underlying these patterns. A theory of symbol production is proposed based on a consideration of constraints in neural space. The theory is related to inner speech and thought.

A neural basis for symbol development.

Understanding of cognitive function and dysfunction depends on a knowledge of the neural substrate for symbol formation. Despite a vast literature on the nature of symbolism, fundamental neurophysiological mechanisms underlying the ontogeny of symbol formation have been neglected. This paper develops a theory outlining the formation and evolution of a symbol couched in terms of the neural substrate.

Neuropathological findings in a case of chronic inflammatory polyneuropathy.

A 52-year-old woman presented with increasing pain, weakness, and paraesthesiae of four months' duration in the lower limbs. She suffered from chronic obstructive airways disease and hypertension. Neurological examination revealed wasting of the quadriceps muscles, weakness of the lower limbs, and absent ankle jerks. The sensory examination was normal. Full blood count, ESR, biochemical, immunological, and viral studies, urinary heavy metal assays, and cerebrospinal fluid examination were normal. Nerve conduction studies were consistent with a sensorimotor neuropathy, and electromyographic sampling was consistent with acute denervation. A sural nerve biopsy showed axonal degeneration and segmental demyelination. One month after admission, she developed carbon dioxide retention. Her weakness spread to affect the upper limbs, and she could not be resuscitated after a cardiac arrest three months after admission. General autopsy examination revealed bronchopneumonia. Neuropathological examination showed a lymphocytic infiltrate in the nerve roots of the cauda equina, the lumbosacral plexus, and the sural and vagal nerves. Increased cellularity and collagen were evident in these nerves. A diagnosis of chronic inflammatory polyneuropathy was made. The neuropathology of this entity is discussed.

The role of atheromatous plaque rupture in the genesis of myocardial infarction.

UNLABELLED: The rupture of advanced atheromatous plaques initiates a significant number of cases of coronary artery thrombosis and subsequent myocardial infarction. HYPOTHESIS: The range of outcomes following plaque rupture is determined to a large extent by the interaction between the turbulent arterial stream and the visco-elastic properties of the extruded atheromatous material. Thrombosis is a secondary event. Research into the visco-elastic behaviour of atheromatous material may predict predisposition to myocardial infarction.

Post-encephalitic Parkinsonism: current experience.

The diagnosis of post-encephalitic Parkinsonism is rarely entertained today. In this paper we discuss eight recent patients, six of whom presented in the last 20 years, that conform to the diagnosis of encephalitis lethargica. The clinical features by which the diagnosis may be made are defined so that a contemporary definition of this disorder may be attained.

Differential contributions of major lipid components of atheroma to outcome of cerebral atheroembolism. A study in an animal model.

Cerebral atheroembolism, in which mainly lipid emboli are released from rupturing atheromatous plaques, may occur without apparent effect, or result in cerebral ischemia and infarction. The reasons behind these unpredictable consequences were sought in the interaction, in vitro and in an animal model, between the main lipid components of advanced plaques. Pure preparations of representative lipids were each harmless when embolized into the cerebral circulation. In contrast, combinations in proportions similar to those in advanced human plaques caused infarction, whether these were synthetic mixtures or extracts from plaques of the entire lipid fraction. The most important physical interaction between the lipids was aggregation of crystals by oils. Between cholesterol and the mainly liquid esters, this created in vitro a range of glutinous aggregates. Triglyceride lowered the melting point of esters, increasing their oiliness, and reduced the cohesiveness of aggregates in the face of operative mechanical forces through a fall in viscosity. Phospholipid, acting principally as an emulsifying agent, promoted dispersion of the oil, secondarily freeing the crystals from its aggregating effect. In the plaque, the balance of these factors will determine the size and number of particles likely to embolize, and, therefore, the clinical outcome should the plaque rupture.

Computerized tomographic appearance of hypertensive encephalopathy.

The computerized tomographic scan in a case of hypertensive encephalopathy showed widespread areas of diminished density in the white matter, mainly in the upper and posterior parts of the hemispheres. The abnormalities resolved within three months of the institution of treatment. We suggest that the low-density areas are focal collections of edema fluid extravasated through ischemic segments of the vessel wall.

Cholesterol crystal embolization in rat brain: a model for atheroembolic cerebral infarction.

Acute and delayed effects of embolizing cerebral surface vessels with cholesterol crystals were studied by direct observation in anesthetized rats and rabbits, using an open-skull technique, and by histological examination of brains at intervals of one day and one week following embolization. The number and size spectrum of crystals, which were infused into the ipsilateral internal carotid artery, were believed to approximate those released by a rupturing large atheromatous plaque in man, but the other lipid materials contained in such plaques were intentionally excluded. It was found that cholesterol crystals had only limited ability to impede blood flow in the 20--80 mu diameter arteries in view. They were also inert within the lumen, causing no vessel wall reaction even after a week; nor was any evidence seen of a thrombogenic effect. Local caliber changes in the containing artery were reproducibly seen, with dilatation of the arterial segment proximal to the embolus and narrowing of the segment in front. These changes appeared to represent an active response of the vessel wall, rather than a passive response to alterations in intraluminal pressure. The difficulty in subsequently locating cholesterol emboli histologically was confirmed. Possible therapeutic implications for atheroembolic cerebral infarction in man were discussed.