Continuous intraduodenal infusion of the levodopa/carbidopa enteral gel as monotherapy is safe and clinically superior to a number of individually optimized combinations of conventional oral and subcutaneous medications in patients with motor fluctuations. Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease.

Gender symptom differences were studied in 948 subjects with Parkinson's disease (PD) using a questionnaire covering the most common symptoms associated with PD at debut (SP-1) and at present (SP-2). The symptoms most frequently reported by both genders were: tremor, fumblingness, writing problems, rigidity and fatigue. At SP-1 females reported neck-pain and low back pain more frequently than males. At SP-2 subjects reported an increased number of symptoms. The following symptoms were more frequent among males than females: writing difficulties, fumblingness, gait problems, speech problems, increased flow of saliva, lack of initiative. Sleep problems were common in both sexes with inability to turn in bed and calf muscle cramps in a high percentage. A majority of female subjects find their symptoms (e.g. depression) constantly distressing. Although depression is not one of primary reported symptoms (36%) attention is called for, due to the problem with compliance to treatment regimes. About 30% do not report having tremor and rigidity. This study indicates the usefulness of a symptom profile instrument capable of capturing the many symptoms involved in PD. Such an instrument could be used to detect apparent mistakes in medication and thereby increase the function and quality of life for the individual.

Changes in striatal binding of [11C]raclopride, a dopamine D2 receptor antagonist, induced by acute levodopa administration, were evaluated with PET in 10 patients with idiopathic Parkinson's disease (PD). The patients were scanned on two occasions: drug-free and 15 minutes after a 5-minute intravenous infusion of 3 mg/kg levodopa. Levodopa administration produced reductions in striatal [11C]raclopride uptake index with a rostrocaudal gradient. The most pronounced reduction was found in the posterior putamen (to 82% of baseline), followed by the anterior putamen (to 88% of baseline) and the caudate nucleus (to 94% of baseline). The magnitude of [11C]raclopride uptake index reduction correlated with drug-free disability. Moreover, in four hemiparkinsonian patients, a reduction in [11C]raclopride uptake index was measured in the putamen contralateral to the parkinsonian symptoms. The present results demonstrate a positive correlation between striatal dopaminergic nerve-terminal deficiency and the capacity for levodopa to increase synaptic dopamine and displace [11C]raclopride binding, which corresponds to an accelerated amine turnover in dopamine-depleted striatal tissue. We therefore suggest that dopaminergic degeneration in PD is paralleled by a progressive acceleration of amine turnover. This mechanistic consequence of nigrostriatal degeneration, the selective restoration of synaptic dopaminergic neurotransmission in denervated striatal subregions, may explain the effectiveness of levodopa in producing symptomatic benefits in early PD. However, we also suggest that in the vastly denervated striatum, as in advanced PD, an excessive acceleration of amine turnover results in swings in levodopa-induced synaptic dopamine levels that are far beyond normal. This phenomenon most likely plays a key role in the pathogenesis underlying the development of motor-response complications in PD.

The distribution of motor endplates in biceps brachii, tibialis anterior, and sartorius muscles from human adults was studied by staining longitudinal cryosections of whole muscle for cholinesterase. A special freezing technique was used to prevent the muscle from cracking before sectioning on a heavy cryostat microtome. The results from a large number of cryosections from biceps brachii and tibialis anterior muscles were analyzed by a computer and the topographical distributions of endplates in different views of the muscles were reconstructed. In the biceps brachii muscle, the endplates formed a fairly distinct, slightly V-shaped band through the middle of the two heads. In the tibialis anterior muscle, the majority of the endplates were superficially distributed along the whole muscle. In the longitudinal sections from the middle part of the muscle, they gave the pattern of a parabola with its apex at the proximal end of the muscle. In the sartorius muscle, the endplates were scattered throughout the muscle and no endplate band was observed. The findings are in accordance with results obtained 30 years ago in investigations of muscle from small children and stillborn infants.

The safety of enteral infusion of levodopa/carbidopa formulated as a gel suspension was found acceptable. For most patients, the technical challenges posed by the enteral infusion system were offset by the improvement in motor fluctuations and dyskinesias offered by this technique.

Two Tanzanian patients with konzo were severely disabled by a non-progressive spastic paraparesis, since the sudden onset during an epidemic six years earlier. At the time of onset they had a high dietary intake of cyanide from exclusive consumption of insufficiently processed bitter cassava roots.

1. A new method for perfusing a 10 cm segment of jejunum in humans has been used in seven subjects to study the effect of the amino acid L‐ leucine (40 mM) on the intestinal absorption of levodopa (2.5 mM). The tube contains six channels and has two inflatable balloons, which enable a perfusion of a closed and defined segment of the proximal small intestine. 2. L‐leucine decreased the intestinal absorption of levodopa from 40 +/‐ 19 to 21 +/‐ 15% but was without effect on the absorption of antipyrine, benserazide and D‐glucose. 3. We confirm that levodopa is absorbed by the active transport system normally responsible for the absorption of large neutral amino acids (LNAA) in humans. Oral absorption by passive diffusion, probably by the paracellular route, might also occur for levodopa in the proximal part of the small intestine.

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