Visual signs and symptoms of Parkinson's disease

Parkinson's disease (PD) is a common disorder of middle-aged and elderly people, in which there is degeneration of the extra-pyramidal motor system. In some patients, the disease is associated with a range of visual signs and symptoms, including defects in visual acuity, colour vision, the blink reflex, pupil reactivity, saccadic and smooth pursuit movements and visual evoked potentials. In addition, there may be psychophysical changes, disturbances of complex visual functions such as visuospatial orientation and facial recognition, and chronic visual hallucinations. Some of the treatments associated with PD may have adverse ocular reactions. If visual problems are present, they can have an important effect on overall motor function, and quality of life of patients can be improved by accurate diagnosis and correction of such defects. Moreover, visual testing is useful in separating PD from other movement disorders with visual symptoms, such as dementia with Lewy bodies (DLB), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Although not central to PD, visual signs and symptoms can be an important though obscure aspect of the disease and should not be overlooked.

Subthalamic nucleus neurones in slices from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mice show irregular, dopamine-reversible firing pattern changes, but without synchronous activity

The loss of dopamine in idiopathic or animal models of Parkinson's disease induces synchronized low-frequency oscillatory burst-firing in subthalamic nucleus neurones. We sought to establish whether these firing patterns observed in vivo were preserved in slices taken from dopamine-depleted animals, thus establishing a role for the isolated subthalamic-globus pallidus complex in generating the pathological activity. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) showed significant reductions of over 90% in levels of dopamine as measured in striatum by high pressure liquid chromatography. Likewise, significant reductions in tyrosine hydroxylase immunostaining within the striatum (>90%) and tyrosine hydroxylase positive cell numbers (65%) in substantia nigra were observed. Compared with slices from intact mice, neurones in slices from MPTP-lesioned mice fired significantly more slowly (mean rate of 4.2 Hz, cf. 7.2 Hz in control) and more irregularly (mean coefficient of variation of inter-spike interval of 94.4%, cf. 37.9% in control). Application of ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonopentanoic acid (AP5) and the GABAA receptor antagonist picrotoxin caused no change in firing pattern. Bath application of dopamine significantly increased cell firing rate and regularized the pattern of activity in cells from slices from both MPTP-treated and control animals. Although the absolute change was more modest in control slices, the maximum dopamine effect in the two groups was comparable. Indeed, when taking into account the basal firing rate, no differences in the sensitivity to dopamine were observed between these two cohorts. Furthermore, pairs of subthalamic nucleus cells showed no correlated activity in slices from either control (21 pairs) or MPTP-treated animals (20 pairs). These results indicate that the isolated but interconnected subthalamic-globus pallidus network is not itself sufficient to generate the aberrant firing patterns in dopamine-depleted animals. More likely, inputs from other regions, such as the cortex, are needed to generate pathological oscillatory activity. © 2006 IBRO.

Gallium-transferrin binding in treated and untreated Parkinson's disease

The binding of gallium (Ga) to transferrin (Tf) was studied in plasma from control patients, in patients with untreated Parkinson's disease (PD) and in patients with PD treated either with levodopa (L-dopa) alone or in combination with selegiline. Mean percentage Ga-Tf binding was significantly reduced in untreated and treated PD compared with controls. Binding, however, was significantly greater in treated than in untreated patients. There was no difference in binding between patients treated with L-dopa alone and those treated with L-dopa and selegiline. The data support the hypothesis that oxidation reactions may be of pathogenic significance in PD.

The visual complications of Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disorder affecting middle-aged and elderly people. The disorder is of particular interest to Optometrists because it is associated with a range of visual problems including defects in eye movement and pupillary function. This article reviews the visual complications of PD and the pathological changes in the eye and brain which may explain these symptoms.

Does the neurodegeneration of Alzheimer’s disease spread between visual cortical regions B17 and B18 via the feedforward or feedback short cortico-cortical projections?

The laminar distribution of senile plaques (SP) and neurofibrillary tangles (NFT) was studied in areas B17 and B18 of the visual cortex in 18 cases of Alzheimer’s disease which varied in disease onset and duration. The objective was to test the hypothesis that SP and NFT could spread via either the feedforward or feedback short cortico-cortical projections. In area B17, the mean density of SP and NFT reached a maximum in lamina III and in laminae II and III respectively. In B18, mean SP density was maximal in laminae III and IV and NFT density in laminae II and III. No significant correlations were observed in any cortical lamina between the density of SP and patient age. However, the density of NFT in laminae III, IV and VI in B18 was negatively correlated with patient age. In addition, in B18, the density of SP in lamina II and lamina V was negatively correlated with disease duration and disease onset respectively. Although these results suggest that SP and NFT might spread between B17 and B18 via the feedforward short cortico-cortical projections, it is also possible that the longer cortico-cortical and cortico-subcortical connections may be involved.

Parkinson's disease Part 1: symptoms, diagnosis and changes in the brain

Parkinson's disease is a common neurodegenerative disorder of middle-aged and elderly people. There are two aspects of the disease of special interest to optometrists. First, visual problems may be present in a proportion of patients with the disease. In addition, the disease is treated by a variety of drugs, some of which may have ocular complications. This article describes the incidence, symptoms, diagnosis, causes and changes in the brain in Parkinson's disease.

Parkinson's disease Part 2: visual aspects

There are two aspects of Parkinson's disease specifically discussed in this article. First, visual symptoms are present in a proportion of patients with the disease and it is important that these are recognised. Second, Parkinson's disease can be successfully treated with drugs, but some of the drugs have ocular side effects and optometrists need to be aware of the signs of ocular complication in these patients.

Serum neopterin levels and gallium transferrin binding in Parkinson's disease

The unconjugated pterin neopterin is secreted by macrophages activated by interferon-gamma and hence, the level of neopterin in serum may be used as a marker of a cellular immune response in a patient. Serum neopterin levels were measured by high performance liquid chromatography (HPLC) in 28 Parkinson's disease (PD) patients and 28 age and sex matched controls. The level of serum neopterin was significantly elevated in PD compared with controls suggesting immune activation in these patients. The level of neopterin was negatively correlated with the level of binding of gallium to transferrin (Tf) but unrelated to the level of iron binding. Hence, in PD, it is possible that a cellular immune response may be important in the pathogenesis of the disease. One effect of the cellular immune response may be a reduction in the binding of metals other than iron to Tf and this could also be a factor in PD.

Visual signs and symptoms of Parkinson's disease

There are two aspects of PD of particular interest to optometrists. First, PD patients can develop a range of visual problems including those affecting eye movement, pupillary function, and in complex visual functions involving the ability to judge distance or make out the shape of an object. Second, the symptoms of PD can be treated successfully using a variety of drugs, some of which have significant ocular adverse reactions (OAR). This article describes the general features of PD, the dopamine neurotransmitter system and its relevance to eye symptoms, the visual symptoms reported in PD, and the OAR that have been reported.

Metal binding to transferrin and immune reactions in Parkinson's disease

The binding of iron (59Fe) and gallium (67Ga) to the plasma protein transferrin (Tf) was investigated by G75 gel filtration chromatography in control patients and treated and untreated patients with Parkinson's disease (PD). Fe-Tf binding was 100% in all controls and PD patients suggesting that a defect in Fe-Tf binding was not involved in the aetiology of PD. Ga-Tf binding was significantly reduced in both untreated and treated PD patients compared to controls. In addition, treated PD patients had significantly higher Ga-Tf binding than untreated patients. A reduction in metal binding to Tf could result in the increase of a low molecular weight species which may more readily enter the CNS. Alternatively, it could lead to a decrease in the transport of essential metals into the brain via the Tf receptor system. A significant elevation in neopterin was demonstrated within the plasma of untreated PD patients compared to controls suggesting the activation of a cellular immune response. Furthermore, plasma neopterin was lower in treated compared to untreated PD patients, although the difference was not significant. There was no evidence for the activation of the humoral immune response in untreated or treated PD patients as measured by circulating immune complex (CIC) levels within the plasma. An inverse relationship between Ga-Tf binding and neopterin was observed in untreated PD patients. The addition of oxidants in the form of potassium permanganate and activated manganese dioxide reduced Ga-Tf binding in control plasma. However, relatively little response was observed using monocyte preparations. The results suggest that oxidants produced by activation of the cellular immune system could damage the Tf molecule thereby reducing its ability to bind metals.

Electrophysiological studies of the visual pathways in Alzheimer's and Parkinson's disease

It is known that parallel pathways exist within the visual system. These have been described as magnocellular and parvocellular as a result of the layered organisation of the lateral geniculate nucleus and extend from the retina to the cortex. Dopamine (DA) and acetylcholine (ACH) are neurotransmitters that are present in the visual pathway. DA is present in the retina and is associated with the interplexiform cells and horizontal cells. ACH is also present in the retina and is associated with displaced amacrine cells; it is also present in the superior colliculus. DA is found to be significantly depleted in the brain of Parkinson's disease (PD) patients and ACH in Alzheimer's disease (AD) patients. For this reason these diseases were used to assess the function of DA and ACH in the electrophysiology of the visual pathway. Experiments were conducted on young normals to design stimuli that would preferentially activate the magnocellular or parvocellular pathway. These stimuli were then used to evoke visual evoked potentials (VEP) in patients with PD and AD, in order to assess the function of DA and ACH in the visual pathway. Electroretinograms (ERGs) were also measured in PD patients to assess the role of DA in the retina. In addition, peripheral ACH function was assessed by measuring VEPs, ERGs and contrast sensitivity (CS) in young normals following the topical instillation of hyoscine hydrobromide (an anticholinergic drug). The results indicate that the magnocellular pathway can be divided into two: a cholinergic tectal-association area pathway carrying luminance information, and a non-cholinergic geniculo-cortical pathway carrying spatial information. It was also found that depletion of DA had very little effect on the VEPs or ERGs, confirming a general regulatory function for this neurotransmitter.

Visual symptoms in Parkinson's disease

Parkinson’s disease (PD) is a common disorder of middle-aged and elderly people in which degeneration of the extrapyramidal motor system causes significant movement problems. In some patients, however, there are additional disturbances in sensory systems including loss of the sense of smell and auditory and/or visual problems. This article is a general overview of the visual problems likely to be encountered in PD. Changes in vision in PD may result from alterations in visual acuity, contrast sensitivity, colour discrimination, pupil reactivity, eye movements, motion perception, visual field sensitivity and visual processing speeds. Slower visual processing speeds can also lead to a decline in visual perception especially for rapidly changing visual stimuli. In addition, there may be disturbances of visuo-spatial orientation, facial recognition problems, and chronic visual hallucinations. Some of the treatments used in PD may also have adverse ocular reactions. The pattern electroretinogram (PERG) is useful in evaluating retinal dopamine mechanisms and in monitoring dopamine therapies in PD. If visual problems are present, they can have an important effect on the quality of life of the patient, which can be improved by accurate diagnosis and where possible, correction of such defects.