The pallidopyramidal syndromes: nosology, aetiology and pathogenesis.

PURPOSE OF REVIEW: The aims of this review is to suggest a new nomenclature and classification system for the diseases currently categorized as neurodegeneration with brain iron accumulation (NBIA) or dystonia-parkinsonism, and to discuss the mechanisms implicated in the pathogenesis of these diseases. RECENT FINDINGS: NBIA is a disease category encompassing syndromes with iron accumulation and prominent dystonia-parkinsonism. However, as there are many diseases with similar clinical presentations but without iron accumulation and/or known genetic cause, the current classification system and nomenclature remain confusing. The pathogenetic mechanisms of these diseases and the causes of gross iron accumulation and significant burden of neuroaxonal spheroids are also elusive. Recent genetic and functional studies have identified surprising links between NBIA, Parkinson's disease and lysosomal storage disorders (LSD) with the common theme being a combined lysosomal-mitochondrial dysfunction. We hypothesize that mitochondria and lysosomes form a functional continuum with a predominance of mitochondrial and lysosomal pathways in NBIA and LSD, respectively, and with Parkinson's disease representing an intermediate form of disease. SUMMARY: During the past 18 months, important advances have been made towards understanding the genetic and pathological underpinnings of the pallidopyramidal syndromes with important implications for clinical practice and future treatment developments.

The diagnosis of Parkinson's disease.

The correct diagnosis of Parkinson's disease is important for prognostic and therapeutic reasons and is essential for clinical research. Investigations of the diagnostic accuracy for the disease and other forms of parkinsonism in community-based samples of patients taking antiparkinsonian medication confirmed a diagnosis of parkinsonism in only 74% of patients and clinically probable Parkinson's disease in 53% of patients. Clinicopathological studies based on brain bank material from the UK and Canada have shown that clinicians diagnose the disease incorrectly in about 25% of patients. In these studies, the most common reasons for misdiagnosis were presence of essential tremor, vascular parkinsonism, and atypical parkinsonian syndromes. Infrequent diagnostic errors included Alzheimer's disease, dementia with Lewy bodies, and drug-induced parkinsonism. Increasing knowledge of the heterogeneous clinical presentation of the various parkinsonisms has resulted in improved diagnostic accuracy of the various parkinsonian syndromes in specialised movement-disorder units. Also genetic testing and various other ancillary tests, such as olfactory testing, MRI, and dopamine-transporter single-photon-emission computed-tomography imaging, help with clinical diagnostic decisions.

Catatonia and other motor syndromes in a chronically hospitalized psychiatric population.

BACKGROUND: To determine the motor characteristics of chronic catatonia, catatonia and other motor disorders were systematically rated in a long-term hospitalized sample. METHOD: Chronically hospitalized psychiatric inpatients (N = 42) with a clinical diagnosis of catatonic schizophrenia (295.2X) were rated for catatonia with a novel 23-item catatonia rating scale, and for parkinsonism, dyskinesia and akathisia using standard rating scales with scale-based criteria for case definition. RESULTS: Catatonia was the sole motor syndrome in nine cases (21%), co-existed with parkinsonism in five (12%), tardive dyskinesia in four (10%), and both parkinsonism and tardive dyskinesia in 10 (24%). There was no correlation between total scores across the four rating scales. 'Rigidity' was the sole catatonic sign which overlapped with other scales. The symptom profile of catatonia in this chronic sample was similar to previous reports based on acutely ill patients. CONCLUSION: Catatonia is distinguishable from other motor disorders in chronic psychiatric patients using the 23-item catatonia rating scale. The features of chronic catatonia are described, and the distribution of catatonic signs is similar for chronic and acute catatonia.

[Atypical Parkinson syndrome]. / Atypische Parkinson-Syndrome.

Various clinico-pathological studies have shown that appr. 20% of patients with a clinical diagnosis of idiopathic Parkinson's disease (IPD) may have neuropathological evidence of alternative causes of parkinsonism. Most of these misdiagnosed "IPD" patients meet clinical criteria for either multiple system atrophy (MSA), or progressive supranuclear palsy (PSP), or corticobasal degeneration (CBD). A careful history and physical examination, as well as follow-ups and selected investigations are essential for an accurate clinical diagnosis of these atypical parkinsonian syndromes. The following paper therefore provides a review of clinical features and diagnostic findings in MSA, PSP and CBD, in order to facilitate recognition of these patients.

Genetics of movement disorders.

Trinucleotide repeat expansions or unstable mutations are the cause of a growing number of hereditary movement disorders, especially inherited ataxias. Diagnostic practice as well as disease classifications have altered accordingly. Genes responsible for "Parkinsonian plus' syndromes and episodic movement disorders have also been recently mapped.

Movement disorders in multiple sclerosis.

Movement disorders (MD), other than tremor, associated with multiple sclerosis (MS) occur infrequently. We report 14 new cases of whom nine had dystonia, three parkinsonism, and two had myoclonus. We also reviewed 135 such cases from the literature. From an analysis of the individual MDs and the site of the lesions described, we conclude that paroxysmal dystonias (tonic spasms), ballism/chorea, and palatal myoclonus can be caused by demyelinating lesions. Parkinsonism, dystonia, and other types of myoclonus, however, often appear to be coincidental.

Serum and urinary manganese levels in patients with Parkinson's disease.

To elucidate the possible role of manganese in the risk of developing Parkinson's disease (PD), we compared serum levels of manganese, and 24-h manganese excretion by urine in 29 PD patients and in 27 matched controls. We also measured chromium and cobalt in the same samples. All these values did not differ significantly between the groups, they were not influenced by antiparkinsonian drugs, and they did not correlate with age, age at onset and duration of the PD, scores of the Unified PD Rating Scale or the Hoehn & Yahr staging in the PD group. These results might suggest that serum levels and urinary excretion of manganese are apparently unrelated to the risk of developing PD.

The prevalence of parkinsonism in Italy: an epidemiological survey of the disease in general practice. The Italian General Practitioner Study Group (IGPSG).

The prevalence and characteristics of parkinsonism have been assessed in two separate geographic areas in Italy (Arcisate and San Giovanni Rotondo). A total of 28,377 patients of 23 general practitioners (GPs) were the reference population. Fifty-eight patients were traced by the GP as having typical parkinsonian features or being treated with antiparkinson drugs. Among 53 subjects, 21 of them untreated, parkinsonism was subsequently confirmed neurologically. The overall crude prevalence rate was 1.87 cases per 1,000 (Arcisate 1.81; San Giovanni Rotondo 2.01). The age- and sex-adjusted prevalence rates were 1.84 in Arcisate and 2.04 in San Giovanni Rotondo. After exclusion of drug-related parkinsonism, the rates were 1.48 and 1.90, respectively. Even with some inconsistencies within the two study areas, the prevalence tended to be higher in San Giovanni Rotondo, to prevail in women, and to increase significantly with age. Presumed etiological factors for parkinsonism were recorded in 34% of the cases (mostly drugs). In two thirds of the cases the disease ran a mild course. The present study shows that the GP proves a valuable reference for surveys of parkinsonism in Italy.

[Epidemiology and therapy of Parkinson disease in inpatient nursing homes]. / Epidemiologie und Therapie des M. Parkinson in der stationären Altenhilfe.

In 12 nursing homes for older people epidemiological and therapeutic data of patients with Parkinson's disease were collected. The mean rate of Parkinson's disease in all inhabitants was 12.5%, the mean clinical disability was 15.3 +/- 4.5 (Webster score). The mean age was very old (81.3 +/- 7.8 years). All patients showed one or more different diseases. The medical treatment was often not in agreement with symptoms. Physical therapy was applied only in 33% of patients. These and further data support the thesis that patients with Parkinson's disease in nursing homes may benefit from therapeutic patterns.

Clinical diagnosis of Parkinson's disease. Proposal of diagnostic subgroups classified at different levels of confidence.

The objective of this paper is to evaluate the accuracy of conventional diagnostic criteria for Parkinson's disease and give an overview of alternative causes to parkinsonian syndromes. We also propose a new approach to the clinical diagnosis of Parkinson's disease, which may improve the diagnostic accuracy. The available information on autopsy findings in patients clinically diagnosed as Parkinson's disease shows that 20 to 30% of these patients do not have the typical neuropathological features with Lewy bodies and cell loss in the substantia nigra. The use of selected additional clinical criteria improves the diagnostic accuracy, however, at the cost of rejecting a rather large group of patients with idiopathic disease verified by autopsy. Based on this fact and a review of the literature on parkinsonian syndromes that may be confused with idiopathic Parkinson's disease, we propose criteria for diagnostic subgroups of the disease classified at different levels of confidence. The suggested diagnostic subgroups are clinical definite, probable and possible Parkinson's disease with a decreasing level of specificity and an increasing level of sensitivity in the different patient categories. The clinical features given special importance in this classification includes presence of resting tremor, asymmetrical disease, response to dopamine agonism and presence of atypical clinical features like dementia and clinical autonomic failure at onset and pyramidal or cerebellar signs at examination. In addition, a history indicating possible etiology for another parkinsonian syndrome will exclude the diagnosis.

[The assessment of the degree of severity and progression in the parkinsonian syndrome]. / Otsenka stepeni tiazhesti i progressirovaniia sindroma parkinsonizma.

A scale is proposed, assessing gravity of the Parkinson's syndrome, elaborated on the basis of the knowledge gained from the authors' own experience and from that of other workers in different parts of the world, to be used in clinical practice and in research. The scale holds 6 items enabling one to assess the extent of motor impairment by the main symptoms: tremor, rigidity and akinesia as well as by the main functional disorders such as walking, facial expression and speech, ability to look after himself/herself. Each item of the scale is ranged according to the 6-score system. A method is proposed, based on the rating scale, of assessing the rate of progression of the Parkinson's syndrome, enabling one to reveal the most progressive symptoms as targets for pharmacotherapy.

Quantification of the cardinal signs of parkinsonism and of associated disability in spouses of sufferers.

Work on the causation of idiopathic parkinsonism is limited by relying on gross clinical definition and lack of studies in the old. A prognostic index for parkinsonism, based on hypo/bradykinesia of gait, had considerably higher values in spouses of 20 aged suffers, who had been cohabiting for about half a century, than in 40 controls. Postural abnormality, measured by standing sway and foot separation during walking, was also greater in these spouses. Marked differences remained after correction for relevant covariates. A blinded rigidity rating was greater in the spouses of sufferers, tremor rating was not. The differences found are difficult to explain by selective mating, learned or reactive behaviour. This suggests that environmental causative influences operate in adult life.

[Translation and application of the Simpson and Angus Scale of Extrapyramidal Symptoms]. / Traduction et utilisation de l'échelle de Simpson et Angus de symptômes extra-pyramidaux.

Extrapyramidal side effects of neuroleptics are important in clinical practice. Study of extra-pyramidal side effects is also of importance for researchers who test new antipsychotic agents or study tardive dyskinesia. A french translation of the Simpson-Angus Rating Scale of extra-pyramidal side effects thus appeared useful. This scale contains 10 items: Gait, Arm dropping, Shoulder shaking. Elbow rigidity, Wrist rigidity, Leg pendulousness, Head dropping, Glabella Tap, Tremor, Salivation. Each item is rated between 0 and 4. A total score is obtained by adding the items and dividing by 10. Scores of up to 0.3 are considered within the normal range. The scale original has been validated in a population of fourteen psychotic inpatients taking, in a double-blind procedure, placebo, haloperidol 6 mg/day or haloperidol 30 mg/day. Patients receiving haloperidol 30 mg/day presented more extrapyramidal symptoms than patients under placebo. The Simpson Angus rating scale has also been shown to have clinical validity and high inter-rater reliability. It can be routinely used in clinical drug evaluation. The french version was used in a population of 30 psychotic inpatients fulfilling the DSM III-R criteria of schizophrenic disorder. Patients were treated for at least two weeks, orally, either with a phenothiazine (chlorpromazine 350 mg) or a butyrophenone (haloperidol 15 mg). 10 of the 30 patients received, in addition, anticholinergic agents (trihexiphenidyl, 5 mg). The french version of The Simpson Angus Rating Scale appeared to be easy to use and not time-consuming. Interraters correlation was high. Patients receiving butyrophenones or phenothiazines had no significantly different ages and sociodemographic characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Levodopa-induced dyskinesias in Parkinson's disease: clinical and pharmacological classification.

Levodopa-induced dyskinesias (LID) in Parkinson's disease (PD) may be classified into three main categories: "On" dyskinesias, diphasic dyskinesias (DD), and "off" periods. The study of 168 parkinsonian patients showed that about half (n = 84) showed one pattern of LID only. A combination of two was present in 68, and 16 had the three presentation patterns. A fairly good correlation between type of dyskinesia and presentation pattern was established. Chorea, myoclonus, and dystonic movements occurred during the "on" period. Dystonic postures, particularly affecting the feet, were mainly present in the "off" period, but a few patients had a diphasic presentation. Repetitive stereotyped movements of the lower limbs always corresponded to DD. Acute pharmacological tests using dopamine agonists (subcutaneous apomorphine 3-8 mg; intravenous lisuride 0.1-0.15 mg) and dopamine antagonists (intravenous sulpiride 200-400 mg and intravenous chlorpromazine 25 mg) were performed in 40 patients. Dopamine agonists enhanced "on" dyskinesias and markedly reduced or abolished "off" period dystonia and DD. Dopamine antagonists reduced all types of LID but usually aggravated parkinsonism. These clinical and pharmacological results indicate that LID in PD are a heterogeneous phenomenon difficult to explain on the basis of a single pathophysiological mechanism.

[Parkinson's disease and parkinsonian syndromes]. / Maladie de Parkinson: et syndromes parkinsoniens.

The parkinsonian syndrome rests on the clinical tripod: akinesia, rigidity, tremor. Akinesia is the key symptom, broadly defined as a difficulty in initiating and performing movements in proportion to their complexity (sophisticated, simultaneous movements) and their duration (repetitive movements). The most frequent cause of the syndrome is Parkinson's disease. Although this diagnosis needs to be confirmed in pathological terms by the loss of neurons and the presence of Lewy's bodies in the substantia nigra, some clinical data enable it to be envisaged with a minimum of errors; these are pure parkinsonian triad, good response to dopatherapy and asymmetrical symptoms. The other causes of parkinsonian syndrome are usually related to the administration of neuroleptic drugs and to degenerative diseases with lesions that are more diffuse than those of Parkinson's disease. In Steele-Richardson-Olzewski disease a parkinsonian syndrome is associated with supranuclear ophthalmoplegia. Multiple systematized atrophy presents under three different clinical aspects: a parkinsonian syndrome without tremor and resistant to L-dopa, suggesting atrophy of the strionigral tract; a parkinsonian syndrome associated with a cerebellar syndrome, suggesting olivo-cerebellar-pontine atrophy, and Shy-Drager disease which includes primary dysautonomy and other neurological syndromes.

Epidemiology of parkinsonism: incidence, classification, and mortality.

An epidemiological study of parkinsonism over a 13-year period (1967 through 1979) is presented, updating previous reports on incidence and trend in the population of Rochester, Minnesota. The overall average annual incidence of parkinsonism per 100,000 population was 20.5, adjusted to the 1970 total United States population, which is virtually unchanged from previous observations. Incidences calculated for each calendar year (1967 through 1979) revealed no remarkable change following the 1976 swine flu vaccination program. There was no sex difference and the peak incidence occurred between ages 75 and 84 years. Idiopathic Parkinson's disease was the most common variant (86%), followed by drug-induced parkinsonism (7%). There were no new cases of postencephalitic parkinsonism diagnosed during the study period. Relative frequency of other types of Parkinson's disease as identified by practicing neurologists is presented. For each case two age- and sex-matched controls were selected from the Rochester population. The survival rates in the controls were comparable to the general population of the west north central region of the United States. The mortalities in the patients were significantly higher (p = 0.001) than the controls and were unchanged from previous rates reported from the same community. In the 69 (50%) patients treated with levodopa, the mortality was comparable to that in controls. The favorable outcome in these cases is attributed to bias resulting from selection of healthier patients for treatment.