Few detailed clinico-pathological correlations of Parkinson's disease have been published. The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported. Seventy six had nigral Lewy bodies, and in all of these Lewy bodies were also found in the cerebral cortex. In 24 cases without Lewy bodies, diagnoses included progressive supranuclear palsy, multiple system atrophy, Alzheimer's disease, Alzheimer-type pathology, and basal ganglia vascular disease. The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82%. These observations call into question current concepts of Parkinson's disease as a single distinct morbid entity.

https://jnnp.bmj.com/content/jnnp/55/3/181.full.pdf

Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.

The ascending monoamine pathways in the rat brain are demonstrated by the pile up of fluorescent material occurring in the axons after various types of lesions. The anatomy of the pathways is outlined in drawings of frontal sections of the brain and the origin and termination of several pathways is determined by studying the anterograde and retrograde degeneration occurring after well localised lesions. It is possible to separate the ascending NA pathways into a dorsal and a ventral bundle of axons. The dorsal bundle innervates the cortex and the hippocampus and the ventral bundle supplies NA nerve terminals to the medulla, the pons, the mesencephalon and the diencephalon. The dorsal bundle is found to originate in the locus coeruleus. Lesions of this nucleus abolish the nerve terminals in all cortical areas and in several other areas of the brain indicating a unique role for the locus coeruleus in influencing the activity of the entire brain. The 5-HT pathways have a distribution similar to the ventral NA pathyway. The course of the nigro-striatal and the meso-limbic DA pathways is presented in detail.

Stereotaxic mapping of the monoamine pathways in the rat brain.

Handbook of psychopharmacology

• Objective. —This synthetic review was performed to demonstrate the utility of frontal-subcortical circuits in the explanation of a wide range of human behavioral disorders. Data Sources. —Reports of patients with degenerative disorders or focal lesions involving frontal lobe or linked subcortical structures were chosen from the English literature. Individual case reports and group investigations from peer-reviewed journals were evaluated. Study Selection. —Studies were included if they described patient behavior in detail or reported pertinent neuropsychological findings and had compelling evidence of a disorder affecting frontal-subcortical circuits. Data Extraction. —Information was used if the report from which it was taken met study selection criteria. Data Synthesis. —Five parallel segregated circuits link the frontal lobe and subcortical structures. Clinical syndromes observed with frontal lobe injury are recapitulated with lesions of subcortical member structures of the circuits. Each prefrontal circuit has a signature behavioral syndrome: executive function deficits occur with lesions of the dorsolateral prefrontal circuit, disinhibition with lesions of the orbitofrontal circuit, and apathy with injury to the anterior cingulate circuit. Depression, mania, and obsessivecompulsive disorder may also be mediated by frontalsubcortical circuits. Movement disorders identify involvement of the basal ganglia component of frontal-subcortical circuits. Conclusions. —Frontal-subcortical circuits mediate many aspects of human behavior.

Frontal-subcortical circuits and human behavior.

This is a proposal of the Movement Disorder Society for a clinical classification of tremors. The classification is based on the distinction between rest, postural, simple kinetic, and intention tremor (tremor during target-directed movements). Additional data from a medical history and the results of a neurologic examination can be combined into one of the following clinical syndromes defined in this statement: enhanced physiologic tremor, classical essential tremor (ET), primary orthostatic tremor, task- and position-specific tremors, dystonic tremor, tremor in Parkinson's disease (PD), cerebellar tremor, Holmes' tremor, palatal tremor, drug-induced and toxic tremor, tremor in peripheral neuropathies, or psychogenic tremor. Conditions such as asterixis, epilepsia partialis continua, clonus, and rhythmic myoclonus can be misinterpreted as tremor. The features distinguishing these conditions from tremor are described. Controversial issues are outlined in a comment section for each item and thus reflect the open questions that at present cannot be answered on a scientific basis. We hope that this statement provides a basis for better communication among clinicians working in the field and stimulates tremor research.

Consensus statement of the Movement Disorder Society on tremor

Regional neuronal loss in the substantia nigra was studied in relation to extrapyramidal symptoms and dementia in 12 patients with idiopathic Parkinson's disease (PD) and in 18 control subjects. Four areas of the right substantia nigra were investigated at the level of the superior colliculus and caudal red nucleus. In Parkinson's disease, the percentages of neurons, from the medial to the lateral part of the substantia nigra, were reduced to 49%, 31%, 41%, and 25% of the control values. The number of neurons in the lateral part showed a negative correlation with the severity of rigidity and hypokinesia, whereas tremor was less noticeable in patients with few neurons. The degree of dementia of the patients had a significant correlation only with neuronal loss in the medial part of the substantia nigra, suggesting, in view of the topographical organization of the neurons in the substantia nigra, that intact projections to the caudate nucleus and limbic and cortical areas are a prerequisite for normal cognitive functioning and that their dysfunction leads to clinical dementia.

Dementia in Parkinson's disease is related to neuronal loss in the medial substantia nigra.

The objective of this study was to examine the quality of life in patients with Parkinson's disease (PD) in a community-based sample (n = 228 patients) using a Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) as a measure. Associations to the variables age, age at onset, duration, clinical stage (Hoehn and Yahr), depression (Zung), and dementia (MMSE) were studied. Women scored significantly lower on five of the eight dimensions of SF-36. Depression, as measured in this study, was more common among parkinsonian women than men. Depression was the factor that was associated most significantly with the experienced quality of life, according to SF-36. With physical functioning, only the clinical stage had a more significant association than depression. To improve the quality of life in patients with PD, it is necessary to make every effort to recognize and relieve the depression of patients with PD.

The quality of life in Parkinson's disease.

This multicentre randomised double-blind 3- to 5-year trial was designed to assess whether initial therapy with cabergoline alone or in combination with levodopa prevents or delays the occurrence of long term motor complications in patients with early Parkinson's disease. Patients eligible for study inclusion (n = 412) had early idiopathic Parkinson's disease (Hoehn and Yahr stages 1 to 3) and had received no previous treatment with levodopa, selegiline or dopamine agonists. Patients were randomised to receive either cabergoline (0.25 to 4 mg once daily) or levodopa (100 to 600 mg/day) titrated over a maximum period of 24 weeks. Once the optimum or maximum tolerated dose was achieved, it was maintained up to the end-point (development of motor complications confirmed at 2 consecutive 3-month visits) or up to a minimum of 3 years' treatment. Open labelled levodopa was added in both treatment arms when the improvement in motor disability [Unified Parkinson's Disease Rating Scale (UPDRS) factor III] decreased below 30% vs baseline. Both treatments improved motor disability, decreasing UPDRS factor III scores and factor II scores for activities of daily living. The development of motor complications (end-point) was significantly less frequent in patients treated with cabergoline than in levodopa recipients (22% vs 34%; p < 0.02). The relative risk of developing motor complications during treatment with cabergoline was more than 50% lower than with levodopa. Serious adverse events, either drug related or not, were slightly more frequent in cabergoline-treated patients (31%) than in those treated with levodopa (25%). The withdrawal rate in the cabergoline vs levodopa group was 16 vs 13%. In conclusion, the study shows that, in patients with early Parkinson's disease, cabergoline is effective either as monotherapy or combined with levodopa. Moreover, starting treatment with cabergoline significantly delays the development of motor complications.

Early Treatment of Parkinson’s Disease with Cabergoline Delays the Onset of Motor Complications

Oxygen toxicity protecting enzymes in Parkinson's disease: Increase of superoxide dismutase-like activity in the substantia nigra and basal nucleus

An epidemiological study of dementia was carried out in the city of Turku (population 164,568) in Finland. A total of 421 patients with moderate to severe dementia were found. Degenerative dementia, i.e. presenile and senile dementia, was present in 218 patients (51.8 %), and in 152 patients (36.1 %) the dementia was associated with arteriosclerosis, including multi-infarct and combined dementia. The prevalence rate of dementia, all types, was 256 per 100,000 population, and 1,961 per 100,000 population over 65 years old. The age-specific prevalence rates of dementia increased with advancing age from 0.1 % in the age group 55–64 years to 11 % in the age group over 85 years. The peak annual incidence rate for all types of dementia was 58 per 100,000 population, and 447 per 100,000 population over 65 years old. Both prevalence and incidence figures suggested a female preponderance in dementia of degenerative origin and in dementia with associated arteriosclerosis.

Urpo K. Rinne

Papers

Dementia in Parkinson's disease is related to neuronal loss in the medial substantia nigra.

The quality of life in Parkinson's disease.

Early Treatment of Parkinson’s Disease with Cabergoline Delays the Onset of Motor Complications

Oxygen toxicity protecting enzymes in Parkinson's disease: Increase of superoxide dismutase-like activity in the substantia nigra and basal nucleus

Epidemiology of dementia in a Finnish population.