Antecollis is dystonia of the neck resulting in excessive forward flexion, often associated with dysphagia. It is generally associated with the later stages of Parkinson’s disease (PD) and is often refractory to medical and botulinum toxin therapy. We report improvement in antecollis in a PD patient following subcutaneous apomorphine therapy. We report a 70 year old lady with idiopathic PD diagnosed 12 years ago. She presented with unilateral levodopa responsive hand tremor with akinesia and rigidity. 12 months ago, during treatment with levodopa 600 mg daily and pramipexole ER 3 mg daily, she developed acute antecollis over 24 h after a fall with minor head injury. Reduction in pramipexole to 2.25 mg daily made no difference. Over 8 months she developed gradual worsening of antecollis with reduced oral intake, weight loss and reduce mobility. She had visual hallucinations with insight. On examination she had normal neck extensor strength. There was no rigidity and minimal bradykinesia in the extremities. Administration of oral medication via nasogastric tube was ineffective. An apomorphine challenge was performed after pre-treatment with domperidone. There was acute improvement in hand function, rigidity and mobility without speech or neck posture improvement. However, neck posture started to improve 4 h post apomorphine administration. Apomorphine was commenced regularly at 2 mg subcutaneous injections 3 times a day. This was well tolerated with mild generalized dyskinesia and no hallucinations. At 2 and 4 months followup, the patient had significant improvement in swallowing and resolution of antecollis. She was able to feed, transfer herself and play the piano again and gained 8 kilograms. She had presence hallucinations at night with retained insight. At 7 months followup she had recurrence of antecollis and dysphagia which improved following cessation of pramipexole and commencement of an apomorphine 16 h daytime infusion with nocturnal rotigotine patch therapy. Apomorphine therapy may be an useful treatment for antecollis in PD.

Objective To determine whether neuropsychological measures differ between patients with idiopathic Parkinson's disease (PD) who acquire dementia within 10 years of disease onset versus those who acquire dementia later in the disease course, using data from the longitudinal Sydney Multicentre Study of PD.Methods The Sydney Multicentre Study of PD is a cohort of 149 community-living de novo patients with idiopathic PD studied over a 20-year period. Detailed clinical and neuropsychological tests were administered at baseline and at 3, 5, 10, 15 and 20 years, and the dementia status was assessed at each time point. For the present study, the pattern of longitudinal neuropsychological measures was compared between PD patients with the onset of dementia in the middle (5-10 years, mid-stage PD dementia, N=20) or late (>10 years, late-stage PD dementia, N=10) disease stages using analysis of variance and multiple linear regression modelling, and the relationship between age and dementia onset assessed using survival statistics.Results Mid-stage PD dementia patients were differentiated from late-stage PD dementia patients by having greater deficits in vocabulary skills prior to and at dementia onset. The pattern of cognitive deficits following dementia onset are similar, and there is no difference in the age of dementia onset between the different PD groups.Conclusions These data suggest that the evolution of dementia within PD occurs at around 70 years of age, regardless of the time of PD onset, and affects cognitive domains in a similar way, although patients with earlier-onset PD have a preserved linguistic ability prior to dementia onset.

After 20 years follow-up of newly diagnosed patients with Parkinson's disease (PD), 100 of 136 (74%) have died. The mortality rate fell in the first 3 years of treatment, then rose compared to the general population, the standardized mortality ratio from 15 to 20 years reaching 3.1. Drug induced dyskinesia and end of dose failure were experienced by most patients, but the main current problems relate to the non-levodopa responsive features of the disease. Dementia is present in 83% of 20-year survivors. Dementia correlates with increasing age and probably reflects an interplay of multiple pathologies. Seventeen people with dementia had postmortems. Eight had diffuse Lewy bodies as the only cause of dementia, while others had mixed neuropathology. Only one person lives independently and 48% are in nursing homes. Excessive daytime sleepiness is noted in 70%, falls have occurred in 87%, freezing in 81%, fractures in 35%, symptomatic postural hypotension in 48%, urinary incontinence in 71%, moderate dysarthria in 81%, choking in 48%, and hallucinations in 74%. The challenge is to understand the cellular mechanisms underlying the diverse features of advanced PD that go far beyond a lack of dopamine.

The present study describes the pathological progression of longitudinally followed cases with levodopa-responsive Parkinson's disease who came to autopsy during the Sydney Multicenter Study of Parkinson's disease. Standardised clinical and neuropathological assessments over five epochs of time verified three different clinicopathological groups. A group of younger onset patients with a typical long duration clinical course of Parkinson's disease. This group of cases had Lewy body distributions consistent with the Braak staging of disease. In this group, brainstem Lewy bodies dominate in those surviving to 5 years; by 13 years, 50% of cases have a limbic distribution of Lewy bodies; and by 18 years, all will have at least this pathological phenotype. Approximately 25% of cases had an early malignant, dementia-dominant syndrome and severe neocortical disease consistent with dementia with Lewy bodies. The last group had an older onset, shorter survival, and a more complex disease course with higher Lewy body loads and a higher proportion with additional neuropathologies. These cases with higher loads of Lewy bodies and shorter survivals suggest that widespread Lewy body pathology either occurs at the onset of clinical disease or rapidly infiltrates the brain. In these cases with shorter survivals, there was more plaque pathology, supporting a more aggressive and linked phenotype. Our data suggest that the selection of similar study cohorts by pathology alone would not be able to differentiate the three different phenotypes identified. The data are also not consistent with a unitary concept of the pathogenesis of Lewy body disease.

This chapter discusses the syndrome of normal-pressure hydrocephalus (NPH) and explores how it relates to Parkinsonism. It also examines Parkinsonism from the perspective of structural lesions such as arteriovenous malformations (AVMs) and brain tumors. NPH is regarded as a paradoxical disorder in which the ventricles of the brain enlarge, yet the pressure within is not increased. Also, lowering the pressure in the ventricles by inserting a shunt can improve symptoms; however the size of the ventricles is usually unchanged. Idiopathic and secondary forms of NPH are recognized. The main clinical features of NPH include: gait, incontinence, and cognitive changes. The major motor impairment is gait disturbance, which most closely resembles that seen in multilacunar states or frontal-lobe syndromes. As softening of the brain parenchyma by multiple infarcts predisposes to ventricular enlargement, there is considerable overlap between NPH and the multilacunar state. Cortical lesions involving the motor and premotor cortex can cause alterations in fine finger movements similar to what is seen in Parkinsonism.

Assessment of a series of 279 cases with Lewy body disease revealed 14 families having a family history consistent with autosomal dominant inheritance, eight of these with dominant Parkinsonism and six with dominant dementia. Analysis of the age at onset and genetic features in these families revealed significant anticipation only in a subset of parkinsonian families, with no pathological alleles for spinocerebellar ataxias or the common alpha-synuclein or LRRK2 point mutations.

One‐third of the 149 people recruited 15 to 18 years ago in the Sydney Multicenter Study of Parkinson's disease have survived. The original study compared low‐dose levodopa with low‐dose bromocriptine. We now report the problems experienced by people who survive 15 years from diagnosis. The standardized mortality ratio is significantly elevated at 1.86 and is not significantly different between treatment arms. Falls occur in 81% of patients, and 23% sustained fractures. Cognitive decline is present in 84%, and 48% fulfill the criteria for dementia. Hallucinations and depression are experienced by 50%. Choking has occurred in 50%, symptomatic postural hypotension in 35%, and urinary incontinence in 41%. No patient is still employed, and 40% of patients live in aged care facilities. Although approximately 95% have experienced L ‐dopa–induced dyskinesia/dystonia and end of dose failure of medication, in the majority, these symptoms are not disabling. Dyskinesia and dystonia were delayed by early use of bromocriptine, but end‐of‐dose failure appeared at a similar time once L ‐dopa was added. The rate of disease progression is similar in both arms of the study. We conclude that the most disabling long‐term problems of Parkinson's disease relate to the emergence of symptoms that are not improved by L ‐dopa. Neuroprotective interventions in Parkinson's disease should be judged by their ability to improve non‐ L ‐dopa–responsive aspects of the disease, rather than just by their capacity to delay the introduction of L ‐dopa or reduce its associated side effects. © 2004 Movement Disorder Society

Parkinson’s disease (PD) is a human basal ganglia disorder characterised by resting tremor, akinesia, rigidity and postural instability. The major neurochemical deficit is a loss of dopamine from the pigmented cells of the substantia nigra pars compacta. Symptoms arise after approximately 80% loss of nigrostriatal dopamine (Hornykiewicz et al., 1963). Hence, dopamine replacement therapy with levodopa or dopamine agonists constitutes the main therapy for PD, although after several years many patients develop dose-related motor fluctuations, freezing episodes, dyskinesias and/or “on-off” phenomenon, necessitating the search for other therapeutic strategies.

A patient with PD who exhibited disabling tremor and prominent dyskinesia underwent deep brain stimulation (DBS) of the left thalamic ventral intermediate nucleus. The electrode migrated and was replaced but with suboptimal clinical response. Two years later, postmortem analysis found the second electrode tip had entered the thalamic centromedian-parafascicular complex. There was a small thalamotomy and cell loss exceeding that found in PD. Thalamic damage may occur in association with DBS for PD.

Levodopa combined with carbidopa is still the most effective treatment for symptoms of Parkinson's disease. Dopamine agonists, the next most effective class of drugs, can be used alone before the introduction of levodopa or as an adjunct to levodopa.Addition of a peripherally-acting COMT inhibitor or an MAO-B inhibitor to levodopa can reduce motor fluctuations in patients with advanced disease.Amantadine may have mild symptomatic benefit and can decrease levodopa-induced dyskinesias.Anticholinergics are rarely used because of their adverse effects, but can be a useful addition to levodopa for control of tremor and drooling.Subcutaneous apomorphine should be available for rescue use in patients with 'off' episodes. Deep brain stimulation is an option for patients with levodopa-induced motor complications and relatively intact cognition.

We report a case in which typical clinical features of idiopathic Parkinson's disease existed for seven years prior to the development of significant behavioral and cognitive changes and severe dementia. The patient presented with right-sided resting tremor. bradykinesia, and rigidity, which were highly responsive to levodopa. Serial neuropsychological evaluation revealed no evidence of dementia until late in the disease. The patient deteriorated rapidly eight years into the disease, requiring full care. She died 16 years after symptom onset and post-mortem neuropathological analysis revealed Lewy body Parkinson's disease and Picks disease. To our knowledge, this is the first non-familial case with this combination of clinical history and pathologically confirmed disease to be reported in the literature. The absence of a family history of any neurological disease sets this case apart from the recently described genetic cases of frontotemporal dementia with Parkinsonism linked to chromosome 17. In addition, the relatively late onset of dementia in frontotemporal dementia is atypical. While there is considerable debate regarding the cause of dementia in idiopathic Parkinson's disease, our case illustrates that Pick's disease is one such cause. (C) 2001 Movement Disorder Society.

In this 12-week, randomized, open-label, blinded-rater, parallel-group trial, the efficacy, safety, and tolerability of tolcapone and pergolide were compared in parkinsonian patients with a fluctuating response to levodopa. Patients received tolcapone 100 mg three times daily (t.i.d.), with a possible increase to 200 mg t.i.d., or pergolide titrated to a maximum dose of 5 mg/day by week 9 (mean final dose 2.2 mg/day). The trial involved 203 patients. Efficacy variables that decreased from baseline to week 12 with tolcapone and pergolide included "off" time (reduced by 2-3 hours/day), daily levodopa intake, sickness impact profile scores, Parkinson's disease questionnaire (PDQ)-39 scores, and Unified Parkinson's Disease Rating Scale (UPDRS) scores. Improvements in efficacy variables were similar with tolcapone and pergolide, with the exception of improvements in quality of life, which were significantly greater with tolcapone; the relative changes in PDQ-39 score at week 12 were -8.7 and -14.2 (P < 0.05) with pergolide and tolcapone, respectively. Improvements in the investigator's global assessment (IGA) of overall efficacy were recorded in 86% of tolcapone-treated patients and in 78% of pergolide-treated patients. The proportion of patients who withdrew because of adverse events was higher in the pergolide group (15%) than in the tolcapone group (5%). Confusion, hypotension, nausea, constipation, abdominal pain, and dyspepsia occurred more frequently with pergolide, whereas diarrhea and urine discoloration occurred more frequently with tolcapone. Tolcapone was better tolerated than pergolide (P < 0.01) according to the IGA of overall tolerability. We conclude that, in this 3-month study, both tolcapone and pergolide provided improvements in motor fluctuations and allowed reductions in levodopa intake when added to levodopa therapy; intent to treat analysis and a less than maximal dose of pergolide may have biased the results in favor of tolcapone. Tolcapone provided greater improvements in quality of fife, was better tolerated, and had a more favorable adverse-event profile than pergolide.