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Background: Major progress in genetic studies of Parkinson’s disease (PD) and parkinsonism has been achieved in the last two decades. Objective: We provide a brief review of the current status of PARK and non-PARK loci/genes, and discuss two new genes: eIF4G1 and VPS35. Methods: The literature on PARK and non-PARK loci/genes was reviewed and some novel information on two new genes is provided. Results: There are 18 PARK loci. The symptomatic carriers of these genes usually present with parkinsonism, although additional clinical features can be seen during the course of the disease. Carriers of non-PARK loci/genes frequently present with a mixed phenotype that includes parkinsonism and additional clinical features. Carriers of the eIF4G1 and VPS35 genes present with a parkinsonian phenotype. The pathology of eIF4G1 is of the α-synuclein type; the pathology of VPS35 is unknown. Conclusion: The current genetic classification of PD/parkinsonism genes is not ideal. The pathological classification based on the accumulation of particular proteins/inclusions is also misleading since there are kindred with a single mutation but pleomorphic pathology. A better classification of neurodegenerative conditions is needed. It is hoped that the genetic studies will lead to better therapies.

Background: A wide variety of movement disorders may occur as a consequence of the administration of antiepileptic drugs (AEDs). Although it has been suggested that the risk of parkinsonism is 10-fold higher in those taking valproate as compared with other AEDs, there have been no large, systematic trials assessing this. Aim: To establish more precisely the prevalence of and risk factors for developing parkinsonism associated with valproate use,and to assess the occurrence of movement disorders with the newer AEDs. Methods: Patients with epilepsy were recruited from the Toronto Western Hospital Epilepsy Clinic (University of Toronto, Toronto, Ontario, Canada). Each patient was examined by a movement disorder specialist who was blinded to the treatment status of the patient. Results: 201 patients were included. Postural tremor was the most common movement disorder (45%), followed by parkinsonism (4.5%). The odds of having parkinsonism were 5 times higher with valproate than with other AEDs. No single factor predicted the presence of parkinsonism; however, many (5/9) of the patients concurrently used other drugs or had comorbidities that could have caused or exacerbated parkinsonism. None of the newer AEDs were clearly associated with the presence of movement disorders; however, the numbers were too small to make a formal analysis. Conclusion: Although the risk of parkinsonism with valproate is higher than with other AEDs, it is lower than originally reported. The cases available were not enough to accurately comment on the prevalence of movement disorders with the newer AEDs.

Objectives: To examine the development of nocturnal sleeping problems in patients with Parkinson’s disease (PD) over an 8-year period and to study the clinical and demographic correlates of insomnia. Methods: 231 patients were included in a population-based prevalence study in 1993, and re-examined in 1997 and 2001. At all study visits, we applied semi-structured interviews to obtain information on clinical and demographic data, as well as on nocturnal sleeping problems. Standardised rating scales of parkinsonism, depression and cognitive impairment were used. The relationship between insomnia and demographic and clinical variables was analysed using population-averaged logistic regression models for correlated data. 231 patients were included at baseline, 142 were available for re-evaluation in 1997 and 89 patients in 2001. Results: Most nocturnal sleeping problems varied little in prevalence over time, whereas problems related to turning in bed and vivid dreaming or nightmares increased. Insomnia was present in 54–60% of the patients at each of the three study visits and varied considerably in individual patients over time. The presence of insomnia was closely related to disease duration, higher Montgomery–Asberg Depression Rating Scale scores and female sex. Conclusion: Insomnia is a highly frequent complaint in patients with PD. It fluctuates over time in individual patients, and its origin seems to be multifactorial. Physicians should be aware of the high prevalence of insomnia in patients with PD and should examine their patients for a possible coexisting depression.

Background: Olfactory abnormalities are reported in Alzheimer’s disease and Parkinson’s disease. Anosmia appears to be common in dementia with Lewy bodies but not in pure Alzheimer’s disease. Objective: To determine whether anosmia improves discrimination between the Lewy body variant (LBV) of Alzheimer’s disease and “pure” Alzheimer’s disease. Methods: 106 cases of necropsy confirmed pure Alzheimer’s disease (n = 89) or LBV (n = 17) were reviewed. All had received butanol odour threshold testing. Anosmia was defined as a score ⩽1.0 on a 0–9 point scale. Logistic regression analysis was used to model potential predictors (for example, parkinsonism, smoking, hallucinations) of neuropathological diagnosis and anosmia. Results: LBV cases had an increased prevalence of anosmia (65%) compared with Alzheimer’s disease (23%; odds ratio (OR) = 6.3, p = 0.00045), or normal elderly people (6.7%). Within the dementia cases, the negative predictive value (92%) and specificity (78%) of anosmia were both good; sensitivity for detecting LBV was 65%, but the positive predictive value (PPV) was only 35%. Logistic regression models showed anosmia (OR = 5.4, p = 0.005) and visual hallucinations (OR = 7.3, p = 0.007) were strong independent predictors of Lewy body pathology. When anosmia was added as a core feature to consensus diagnostic criteria for probable Lewy body dementia, five additional cases of LBV were detected (29% increased sensitivity), but with four additional false positives (1% increased discrimination, 4% decreased specificity, 33% decreased PPV). Conclusions: Anosmia is very common in LBV. Adding anosmia as a core feature improved sensitivity for detecting LBV, but did not improve discrimination between Alzheimer’s disease and LBV owing to a concomitant increase in false positives.

Background: The seed powder of the leguminous plant, Mucuna pruriens has long been used in traditional Ayurvedic Indian medicine for diseases including parkinsonism. We have assessed the clinical effects and levodopa (l-dopa) pharmacokinetics following two different doses of mucuna preparation and compared them with standard l-dopa/carbidopa (LD/CD). Methods: Eight Parkinson’s disease patients with a short duration l-dopa response and on period dyskinesias completed a randomised, controlled, double blind crossover trial. Patients were challenged with single doses of 200/50 mg LD/CD, and 15 and 30 g of mucuna preparation in randomised order at weekly intervals. l-Dopa pharmacokinetics were determined, and Unified Parkinson’s Disease Rating Scale and tapping speed were obtained at baseline and repeatedly during the 4 h following drug ingestion. Dyskinesias were assessed using modified AIMS and Goetz scales. Results: Compared with standard LD/CD, the 30 g mucuna preparation led to a considerably faster onset of effect (34.6 v 68.5 min; p = 0.021), reflected in shorter latencies to peak l-dopa plasma concentrations. Mean on time was 21.9% (37 min) longer with 30 g mucuna than with LD/CD (p = 0.021); peak l-dopa plasma concentrations were 110% higher and the area under the plasma concentration v time curve (area under curve) was 165.3% larger (p = 0.012). No significant differences in dyskinesias or tolerability occurred. Conclusions: The rapid onset of action and longer on time without concomitant increase in dyskinesias on mucuna seed powder formulation suggest that this natural source of l-dopa might possess advantages over conventional l-dopa preparations in the long term management of PD. Assessment of long term efficacy and tolerability in a randomised, controlled study is warranted.

Objectives: Degeneration of nigrostriatal neurons and subsequent striatal dopamine deficiency produce many of the symptoms of Parkinson disease (PD). Initially restoration of striatal dopamine with oral levodopa provides substantial benefit, but with long term treatment and disease progression, levodopa can elicit additional clinical symptoms, reflecting altered effects of levodopa in the brain. The authors examined whether long term treatment affects the brain's response to levodopa in the absence of these altered clinical responses to levodopa. Methods: Positron emission tomography (PET) measurements were used of brain-blood flow before and after an acute dose of levodopa in three groups: PD patients treated long term with levodopa without levodopa induced dyskinesias, levodopa naive PD patients, and controls. Results: It was found that the PD group treated long term responded to acute levodopa differently from controls in left sensorimotor and left ventrolateral prefrontal cortex. In both regions, the treated PD group had decreased blood flow whereas the control group had increased blood flow in response to levodopa. Levodopa naive PD patients had little or no response to levodopa in these regions. Within the treated PD group, severity of parkinsonism correlated with the degree of abnormality of the sensorimotor cortex response, but not with the prefrontal response. Conclusions: It is concluded that long term levodopa treatment and disease severity affect the physiology of dopaminergic pathways, producing altered responses to levodopa in brain regions associated with motor function.

Background: The presence of Lewy bodies (LB) in the neocortex and limbic system in patients with Parkinson's disease (PD) is commonly thought to be linked with cognitive impairment. The authors present here a series of patients with diagnosis of PD in life and no significant cognitive impairment who, at necropsy, satisfied the current neuropathological criteria for dementia with Lewy bodies (DLB). Methods: Two hundred and seventy six brains with PD pathology were examined at the Queen Square Brain Bank in London between 1993 and 1999. The neuropathological diagnosis was PD, but 117 patients also had sufficient LB involvement above the brain stem to satisfy the current neuropathological criteria for DLB (50 patients had a neuropathological picture consistent with the limbic category of DLB and 67 with neocortical DLB). Forty eight cases were excluded who developed early cognitive impairment together with motor features of parkinsonism, 12 cases for lack of detailed clinical history, and 19 cases with coexistent features of advanced Alzheimer's disease changes. Thirty eight patients (13.8% of the total with PD pathology and 32.5 % of the total with DLB pathology) were found where there was no or very late cognitive impairment reported in the clinical records. Results: Selected cases were 24 men and 14 women, with a mean (SD) age at onset of parkinsonian symptoms of 60.1 (10.1) years and a mean disease duration of 15.3 (5.5) years. At some time during the evolution of the disease 21 patients developed different degrees of cognitive impairment (after a mean disease duration of 12.2 (4.8) years). Clinical diagnosis at death was PD in 10 cases and PD with dementia in 11. In the remaining 17 patients no history of cognitive impairment was ever recorded in life and all of them had a clinical diagnosis of PD at death; in this subgroup, nine patients later revealed a neuropathological picture consistent with limbic (or transitional) category of DLB and eight with neocortical DLB. Interestingly, in all these patients the parkinsonian features including the response to dopaminergic drugs were indistinguishable from classic brain stem PD. Conclusions: The authors demonstrate that the classic pathology of DLB can commonly be seen outside the generally accepted clinical spectrum for DLB and that important factors other than the absolute number of LB in the neocortex and limbic system influence the development of cognitive impairment in PD. Furthermore, the pathology of PD may be indistinguishable from that reported in DLB, suggesting that the two clinicopathological syndromes may be attributable to the same biological abnormality.

To assess the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with advanced Parkinson's disease previously reliant on apomorphine as their main antiparkinsonian medication.Seven patients with motor fluctuations despite optimal medical treatment given as predominantly apomorphine infusion (n=6), or intermittent apomorphine injections (n=1) underwent bilateral STN DBS using frameless stereotactic surgery. Standard assessments of parkinsonism and motor fluctuations, using Unified Parkinson's Disease Rating Scale (UPDRS) were performed before and six months after surgery. Assessments were performed both on and off medication, and postoperative with the stimulators switched on and off.Bilateral STN DBS improved motor scores (UPDRS III) by 61% when off medication (p0.05). Clinical fluctuations (UPDRS IV items 36-39) were reduced by 46.2% (p0.05). Total daily apomorphine dose was reduced by 68.9% (p0.05) and apomorphine infusion via a pump was no longer required in four patients. There were no operative complications. Two patients required treatment for hallucinations postoperatively but there was no significant change in mini-mental state examination.In patients with advanced Parkinson's disease, previously reliant on apomorphine, bilateral STN DBS is an effective treatment to reduce motor fluctuations and enable a reduction in apomorphine use.

Background: Many patients diagnosed with Parkinson's disease are later found to have an erroneous diagnosis, often only when they come to necropsy; conversely, many patients with Parkinson's disease in the community remain undiagnosed. Objective: To assess the validity of a clinical diagnosis of parkinsonism in the general population according to strict published criteria. Methods: As part of a population based study on the prevalence of Parkinson's disease in London, all patients were identified with a diagnosis of parkinsonism, tremor with onset over age 50 years, or who had ever received antiparkinsonian drugs. All patients who agreed to participate were diagnosed according to strict clinical diagnostic criteria, after a detailed neurological interview and examination and discussion of the findings with examination of their video recordings. Follow up information was obtained over a period of at least one year, and atypical cases were reviewed at the end of the study. Results: A diagnosis of probable Parkinson's disease was confirmed in 83% of patients with this diagnosis, including three (2%) in whom atypical features were found that were insufficient to discard a diagnosis of Parkinson's disease. Two additional patients (2%) were found to have possible Parkinson's disease. However, in 15% of patients the diagnosis was unequivocally rejected. Conversely, 13 patients who had previously not been diagnosed with Parkinson's disease (19%) were found to have this disorder. Conclusions: At least 15% of patients with a diagnosis of Parkinson's disease in the population do not fulfil strict clinical criteria for the disease, and approximately 20% of patients with Parkinson's disease who have already come to medical attention have not been diagnosed as such.

Background: 123 I-labelled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ( 123 I-FP-CIT) imaging is a diagnostic tool to help differentiate dementia with Lewy bodies (DLB) from Alzheimer’s disease (AD). However, in animals, cholinesterase inhibitors (ChEi) have been reported to reduce radioligand binding to the striatal dopamine transporter. As ChEi are frequently used in people with dementia, it is important to determine whether their use affects 123 I-FP-CIT uptake in the striatum. Objective: To clarify whether chronic ChEi therapy modulates striatal dopamine transporter binding measured by 123 I-FP-CIT in patients with AD, DLB and Parkinson’s disease with dementia (PDD). Design: Cross sectional study in 99 patients with AD (nine on ChEi, 25 not on ChEi), DLB (nine on ChEi, 19 not on ChEi) and PDD (six on ChEi, 31 not on ChEi) comparing 123 I-FP-CIT striatal binding (caudate, anterior and posterior putamen) in patients receiving compared with those not receiving ChEi, correcting for key clinical variables including diagnosis, age, sex, Mini-Mental State Examination score, severity of parkinsonism and concurrent antidepressant use. Results: As previously described, 123 I-FP-CIT striatal uptake was lower in DLB and PDD subjects compared with those with AD. Median duration of ChEi use was 180 days. 123 I-FP-CIT uptake was not significantly reduced in subjects receiving ChEi compared those not receiving ChEi (mean percentage reduction: AD 4.3%; DLB 0.7%; PDD 6.1%; p = 0.40). ChEi use did not differentially affect striatal 123 FP-CIT uptake between patient groups (p = 0.83). Conclusions: Use of ChEi does not significantly influence the ability of 123 I-FP-CIT imaging to distinguish AD from DLB.

Background: Levodopa (L-dopa) is the gold standard treatment for Parkinson’s disease, but a lack of clear efficacy combined with a perceived liability to neuropsychiatric side effects has limited L-dopa use in patients with parkinsonism and dementia. Therefore, the effect of L-dopa on the cognitive profile of dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD) is unclear. Aim: To ascertain the acute and long-term effects of L-dopa on aspects of attention and cognition in patients with DLB and PDD, and to compare these with the effects in Parkinson’s disease. Method: Baseline cognitive and motor function was assessed off L-dopa in patients with Parkinson’s disease (n = 22), PDD (n = 27) and DLB (n = 11) using standard “bedside” measures and a computerised programme detecting reaction times and accuracy. All patients then underwent an acute L-dopa challenge with subsequent subjective and objective analysis of alertness, verbal recall, reaction times and accuracy. The same parameters were measured after 3 months on L-dopa to assess the prolonged effect. Results: Acute L-dopa challenge considerably improved motor function and subjective alertness in all patients without compromising either reaction times or accuracy, but increased fluctuations were noted in both groups with dementia. Neuropsychiatric scores improved in patients with Parkinson’s disease both with and without dementia on L-dopa at 3 months. Although patients with Parkinson’s disease also had better mean global cognitive function at this time, mean verbal attention and memory deteriorated, and patients with PDD had slower reaction times in some tests. No patient had a marked deterioration over this time. Patients with DLB did not experience any adverse cognitive or neuropsychiatric effects after 3 months of L-dopa treatment. Conclusion: The use of L-dopa in patients with parkinsonism with dementia does not adversely affect cognitive function.

Background: Camptocormia is defined as an abnormal flexion of the trunk that appears when standing or walking and disappears in the supine position. The origin of the disorder is unknown, but it is usually attributed either to a primary or a secondary paravertebral muscle myopathy or a motor neurone disorder. Camptocormia is also observed in a minority of patients with parkinsonism. Objective: To characterise the clinical and electrophysiological features of camptocormia and parkinsonian symptoms in patients with Parkinson’s disease and camptocormia compared with patients with Parkinson’s disease without camptocormia. Methods: Patients with parkinsonism and camptocormia (excluding patients with multiple system atrophy) prospectively underwent a multidisciplinary clinical (neurological, neuropsychological, psychological, rheumatological) and neurophysiological (electromyogram, ocular movement recording) examination and were compared with age-matched patients with Parkinson’s disease without camptocormia. Results: The camptocormia developed after 8.5 (SD 5.3) years of parkinsonism, responded poorly to levodopa treatment (20%) and displayed features consistent with axial dystonia. Patients with camptocormia were characterised by prominent levodopa-unresponsive axial symptoms (ie, axial rigidity, gait disorder and postural instability), along with a tendency for greater error in the antisaccade paradigm. Conclusion: We suggest that (1) the salient features of parkinsonism observed in patients with camptocormia are likely to represent a specific form of Parkinson’s disease and camptocormia is an axial dystonia and (2) both camptocormia and parkinsonism in these patients might result from additional, non-dopaminergic neuronal dysfunction in the basal ganglia.

Background: Mirror movements (MM) are not widely appreciated in parkinsonism and no report has evaluated this clinical sign in detail. Objectives: To define the parkinsonian clinical features associated with MM in patients with early, asymmetric parkinsonism. Methods: Twenty seven patients with early Parkinson’s disease were evaluated using a standardised videotaping protocol. MM were scored from blinded video assessment using a clinical scale that rates the amplitude, distribution, and proportion of mirroring in the less affected limb. Parkinsonian features were combined into axial and lateralised scores using related items of the Unified Parkinson’s Disease Rating Scale. Results: MM were present in 24 of 27 patients. There was a significant linear correlation between the degree of asymmetry of motor deficits and MM on the less affected side. The effect of asymmetry was greater when the proportional rather than the absolute motor difference between sides was largest. Asymmetry in leg rigidity was the most important examination feature in the prediction of contralateral foot mirroring. Conclusions: MM are a clinical feature of the unaffected or less affected side in mild asymmetric parkinsonism. Their presence may be a useful clinical finding in early parkinsonism.

Objective: To assess the accuracy and clinical usefulness of [123I]s-CIT (2s-carbomethoxy-3s-(4-iodophenyl)tropane) SPECT in the differential diagnosis of Parkinson's disease. Subjects: 185 consecutive patients with symptoms of movement disorder were studied. The diagnoses were Parkinson's disease (92), essential tremor (16), vascular parkinsonism (15), various Parkinson plus syndromes (P+) (12), dementia with Lewy bodies (DLB) (5), dystonia (5), drug induced movement disorder (12), and other diagnoses (8). A reference group (psychogenic parkinsonism) comprised 20 subjects with complaints suggesting extrapyramidal disease but with no unequivocal signs on clinical examination and no abnormalities on brain imaging. Results: s-CIT uptake was significantly lower in the whole striatum as well as separately in the putamen and in the caudate nucleus in Parkinson's disease than in the reference group or in drug induced movement disorder, essential tremor, or dystonia. The uptake of s-CIT in the vascular parkinsonism group was heterogeneous and mean s-CIT uptake fell between the reference group and the Parkinson's disease group. In the P+ and DLB groups the striatal uptake ratios overlapped those of the Parkinson's disease group. Conclusions: [123I]s-CIT SPECT may not be as useful a tool in the clinical differential diagnosis of Parkinson's disease as was previously believed, but it was 100% sensitive and specific for the diagnosis in younger patients (age 55 years) specificity was substantially lower (68.5%). This differential specificity reflected the different distribution of differential diagnostic disorders (P+, DLB, vascular parkinsonism) in the older and younger age groups.

Objectives: The authors report the results of detailed investigations into the motor function of a patient who, after a heavy drinking binge and subsequent unconsciousness, respiratory acidosis, and initial recovery, developed parkinsonism characterised by hypophonic speech and palilalia, "fast micrographia", impaired postural reflexes, and brady/akinesia in proximal (but not distal) alternating upper limb movements. Methods: In addition to brain magnetic resonance imaging (MRI), different aspects of motor function were investigated using reaction time (RT) tasks, pegboard and finger tapping tasks, flex and squeeze tasks, movement related cortical potentials (MRCPs), and contingent negative variation (CNV). Cognitive function was also assessed. The results were compared to those previously reported in patients with Parkinson's disease (PD). Results: Brain MRI showed isolated and bilateral globus pallidus (GP) lesions covering mainly the external parts (GPe). These lesions were most probably secondary to respiratory acidosis, as other investigations failed to reveal an alternative cause. The results of the RT tasks showed that the patient had difficulties in preparing and maintaining preparation for a forthcoming movement. MRCP and CNV studies were in line with this, as the early component of the MRCP and CNV were absent prior to movement. The patient's performance on pegboard and finger tapping, and flex and squeeze tasks was normal when performed with one hand, but clearly deteriorated when using both hands simultaneously or sequentially. Conclusions: In general, the present results were similar to those reported previously in patients with PD. This provides further indirect evidence that the output of globus pallidus is of major importance in abnormal motor function in PD. The possible similarities of the functional status of GP in PD and our case are discussed.

Background: Formal laboratory testing of autonomic function is reported to distinguish between patients with Parkinson’s disease and those with multiple system atrophy (MSA), but such studies segregate patients according to clinical criteria that select those with autonomic dysfunction for the MSA category. Objective: To characterise the profiles of autonomic disturbances in patients in whom the diagnosis of Parkinson’s disease or MSA used criteria other than autonomic dysfunction. Methods: 47 patients with parkinsonism and autonomic symptoms who had undergone autonomic laboratory testing were identified and their case records reviewed for non-autonomic features. They were classified clinically into three diagnostic groups: Parkinson’s disease (19), MSA (14), and uncertain (14). The performance of the patients with Parkinson’s disease was compared with that of the MSA patients on five autonomic tests: RR variation on deep breathing, heart rate changes with the Valsalva manoeuvre, tilt table testing, the sudomotor axon reflex test, and thermoregulatory sweat testing. Results: None of the tests distinguished one group from the other with any statistical significance, alone or in combination. Parkinson’s disease and MSA patients showed similar patterns of autonomic dysfunction on formal testing of cardiac sympathetic and parasympathetic, vasomotor, and central and peripheral sudomotor functions. Conclusions: This study supports the clinical observation that Parkinson’s disease is often indistinguishable from MSA when it involves the autonomic nervous system. The clinical combination of parkinsonism and dysautonomia is as likely to be caused by Parkinson’s disease as by MSA. Current clinical criteria for Parkinson’s disease and MSA that direct patients with dysautonomia into the MSA group may be inappropriate.

Objectives: The differential diagnosis between typical idiopathic Parkinson's disease (PD) and the striatonigral variant of multiple system atrophy (MSA-P) is often difficult because of the presence of signs and symptoms common to both forms of parkinsonism, particularly at symptom onset. This study investigated striatal and midbrain findings in MSA-P and PD patients in comparison with normal controls with the use of positron emission tomography (PET) and three dimensional magnetic resonance imaging (3D MRI) based volumetry to increase the differential diagnostic accuracy between both disease entities. Methods: Nine patients with MSA-P, 24 patients with PD, and seven healthy controls were studied by MRI and PET with 6-[18F]-fluoro-L-dopa (FDOPA), [18F]fluoro-deoxyglucose (FDG), and 11-C-Raclopride (RACLO). Striatal and extrastriatal volumes of interest (VOI) were calculated on the basis of the individual MRI data. The PET data were transferred to the VOI datasets and subsequently analysed. Results: MSA-P differed significantly from PD patients in terms of decreased putaminal volume, glucose metabolism, and postsynaptic D2 receptor density. The striatal FDOPA uptake was equally impaired in both conditions. Neither MRI volumetry nor PET imaging of the midbrain region further contributed to the differential diagnosis between PD and MSA-P. Conclusions: The extent and spatial distribution of functional and morphological changes in the striatum permit the differentiation of MSA-P from PD. Both, multi-tracer PET and 3D MRI based volumetry, may be considered equivalent in the assessment of different striatal abnormality in both disease entities. In contrast, MRI and PET imaging of the midbrain does not provide a further gain in diagnostic accuracy.

Objective: To delineate the frequency and nature of dystonia in multiple system atrophy (MSA). Methods: a cohort of 24 patients with clinically probable MSA over the past 10 years were prospectively followed up. Motor features were either dominated by parkinsonism (MSA-P subtype, n=18) or cerebellar ataxia (MSA-C, n=6). Classification of dystonic features and their changes with time was based on clinical observation during 6–12 monthly follow up visits. Parkinsonian features and complications of drug therapy were assessed. Most patients (22/24) died during the observation period. Neuropathological examination was confirmatory in all of the five necropsied patients. Results: At first neurological visit dystonia was present in 11 (46%) patients all of whom had been levodopa naive at this time point. Six patients (25%) exhibited cervical dystonia (antecollis) (MSA-P n=4, MSA-C n=2), five patients (21%) showed unilateral limb dystonia (MSA-P n=4; MSA-C n=1). A definite initial response to levodopa treatment was seen in 15/18 patients with MSA-P, but in none of the six patients with MSA-C. A subgroup of 12 patients with MSA-P developed levodopa induced dyskinesias 2.3 years (range 0.5–4) after initiation of levodopa therapy. Most patients had peak dose craniocervical dystonia; however, some patients experienced limb or generalised dystonia. Isolated peak dose limb chorea occurred in only one patient. Conclusion: The prospective clinical study suggests that dystonia is common in untreated MSA-P. This finding may reflect younger age at disease onset and putaminal pathology in MSA-P. Levodopa induced dyskinesias were almost exclusively dystonic affecting predominantly craniocervical musculature. Future studies are required to elucidate the underlying pathophysiology of dystonia in MSA.

A relatively simple, exact method is described for simultaneously estimating dopamine, dopa, and dopac in urine. The compounds are concentrated on alumina by an abbreviated batch technique and separated by "two solutions" paper electrophoresis at low voltage for 2 h. Fluorophores are developed by condensation with ethylenediamine. The fluorescent bands, eluted into water, are measured fluorometrically. This method was used to estimate the major free metabolites of dopa in urines from parkinsonian and hyperkinetic patients, and normal subjects. Compared with normal controls, dopamine excretion tended to be decreased in patients with parkinsonism, increased in hyperkinetic patients. The sum of the free metabolites (dopamine, dopac, and homovanillic acid) was significantly smaller for the patients with parkinsonism than for normal subjects.