Peter G Bain

Imperial College London, London, ENG, United Kingdom

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Publications (111)434.22 Total impact

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    ABSTRACT: Levodopa-induced dyskinesias (LIDs) are the most common and disabling adverse motor effect of therapy in Parkinson's disease (PD) patients. In this study, we investigated serotonergic mechanisms in LIDs development in PD patients using 11C-DASB PET to evaluate serotonin terminal function and 11C-raclopride PET to evaluate dopamine release. PD patients with LIDs showed relative preservation of serotonergic terminals throughout their disease. Identical levodopa doses induced markedly higher striatal synaptic dopamine concentrations in PD patients with LIDs compared with PD patients with stable responses to levodopa. Oral administration of the serotonin receptor type 1A agonist buspirone prior to levodopa reduced levodopa-evoked striatal synaptic dopamine increases and attenuated LIDs. PD patients with LIDs that exhibited greater decreases in synaptic dopamine after buspirone pretreatment had higher levels of serotonergic terminal functional integrity. Buspirone-associated modulation of dopamine levels was greater in PD patients with mild LIDs compared with those with more severe LIDs. These findings indicate that striatal serotonergic terminals contribute to LIDs pathophysiology via aberrant processing of exogenous levodopa and release of dopamine as false neurotransmitter in the denervated striatum of PD patients with LIDs. Our results also support the development of selective serotonin receptor type 1A agonists for use as antidyskinetic agents in PD.
    The Journal of clinical investigation 02/2014; · 15.39 Impact Factor
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    ABSTRACT: In Parkinson's disease the degree of motor impairment can be classified with respect to tremor dominant and akinetic rigid features. While tremor dominance and akinetic rigidity might represent two ends of a continuum rather than discrete entities, it would be important to have non-invasive markers of any biological differences between them in vivo, to assess disease trajectories and response to treatment, as well as providing insights into the underlying mechanisms contributing to heterogeneity within the Parkinson's disease population. Here, we used magnetic resonance imaging to examine whether Parkinson's disease patients exhibit structural changes within the basal ganglia that might relate to motor phenotype. Specifically, we examined volumes of basal ganglia regions, as well as transverse relaxation rate (a putative marker of iron load) and magnetization transfer saturation (considered to index structural integrity) within these regions in 40 individuals. We found decreased volume and reduced magnetization transfer within the substantia nigra in Parkinson's disease patients compared to healthy controls. Importantly, there was a positive correlation between tremulous motor phenotype and transverse relaxation rate (reflecting iron load) within the putamen, caudate and thalamus. Our findings suggest that akinetic rigid and tremor dominant symptoms of Parkinson's disease might be differentiated on the basis of the transverse relaxation rate within specific basal ganglia structures. Moreover, they suggest that iron load within the basal ganglia makes an important contribution to motor phenotype, a key prognostic indicator of disease progression in Parkinson's disease.
    Parkinsonism & Related Disorders 08/2013; · 3.27 Impact Factor
  • Practical Neurology 05/2013;
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    ABSTRACT: OBJECTIVE: The underlying pathophysiology of tremor in Parkinson disease (PD) is unclear; however, it is known that tremor does not appear to be as responsive to dopaminergic medication as bradykinesia or rigidity. It is suggested that serotonergic dysfunction could have a role in tremor development. METHODS: Using (11)C-DASB PET, a marker of serotonin transporter binding, and clinical observations, we have investigated function of serotonergic terminals in 12 patients with tremor-predominant and 12 with akinetic-rigid PD. Findings were compared with those of 12 healthy controls. RESULTS: Reductions of (11)C-DASB in caudate, putamen, and raphe nuclei significantly correlated with tremor severity on posture and action, but not with resting tremor. The tremor-predominant group also showed reductions of (11)C-DASB in other regions involved in motor circuitry, including the thalamus and Brodmann areas 4 and 10. CONCLUSIONS: Our findings support a role for serotonergic dysfunction in motor circuitries in the generation of postural tremor in PD.
    Neurology 04/2013; · 8.25 Impact Factor
  • Hazel Lote, Geraint N Fuller, Peter G Bain
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    ABSTRACT: 48, XXYY syndrome is a form of sex chromosome aneuploidy that affects between 1 in 18 000 to 1 in 40 000 males. It is not inherited and is diagnosed by karyotyping. It has similarities to 47, XXY Klinefelter's syndrome, with tall stature, micro-orchidism, hypergonadotropic hypogonadism and infertility in males. However, patients with 48, XXYY syndrome also commonly have dental problems, tremor, attention deficit disorder, learning difficulties, allergies and asthma. The tremor is typically reported as an intention tremor (in 71% of patients XXYY aged >20 years with 48), which becomes more common with age and worsens over time.
    Practical Neurology 03/2013;
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    ABSTRACT: Disordered copper metabolism may be important in the aetiology of Parkinsonism, as caeruloplasmin is a key enzyme in handling oxidative stress and is involved in the synthesis pathway of dopamine. The human Cu metabolism of ten Parkinsonism patients was compared to ten healthy controls with the aid of a stable (65)Cu isotope tracer. The analyses of blood serum (65)Cu/(63)Cu ratios yielded individual isotopic profiles, which indicate that the Cu metabolism is less controlled in patients with Parkinsonism. Modelling based on both isotope tracer and total Cu concentrations suggests that 30% of the subjects affected by Parkinsonism have abnormally large Cu stores in tissues. To detect the small differences in Cu metabolism between Parkinsonism and controls, the analysis of stable isotope composition must be performed using multiple-collector inductively coupled plasma mass spectrometry and the associated sample preparation techniques. This pilot investigation supports full-scale medical studies into the Cu metabolism of those with Parkinsonism.
    Metallomics 01/2013; · 4.10 Impact Factor
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    ABSTRACT: Deep brain stimulation (DBS) is a successful surgical therapy used to treat the disabling symptoms of movement disorders such as Parkinson's disease. It involves the chronic stimulation of disorder-specific nuclei. However, the mechanisms that lead to clinical improvements remain unclear. Consequently, this slows the optimization of present-day DBS therapy and hinders its future development and application. We used a computational model to calculate the distribution of electric potential induced by DBS and study the effect of stimulation on the spiking activity of a subthalamic nucleus (STN) projection neuron. We previously showed that such a model can reveal detailed spatial effects of stimulation in the vicinity of the electrode. However, this multi-compartmental STN neuron model can fire in either a burst or tonic mode and, in this study, we hypothesized that the firing mode of the cell will have a major impact on the DBS-induced effects. Our simulations showed that the bursting model exhibits behaviour observed in studies of high-frequency stimulation of STN neurons, such as the presence of a silent period at stimulation offset and frequency-dependent stimulation effects. We validated the model by simulating the clinical parameter settings used for a Parkinsonian patient and showed, in a patient-specific anatomical model, that the region of affected tissue is consistent with clinical observations of the optimal DBS site. Our results demonstrated a method of quantitatively assessing neuronal changes induced by DBS, to maximize therapeutic benefit and minimize unwanted side effects.
    European Journal of Neuroscience 07/2012; 36(2):2252-9. · 3.75 Impact Factor
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    ABSTRACT: Handwriting examinations are commonly performed in the analysis of tremor and Parkinson's disease (PD). We analyzed the accuracy of subjective and objective assessment of handwriting samples for distinguishing 27 PD cases, 22 with tremulous PD, and five with akinetic-rigid PD, from 39 movement-disorder patients with normal presynaptic dopamine imaging (subjects without evidence of dopamine deficiency or SWEDDs; 31 with dystonic tremor (DT), six indeterminate tremor syndrome, one essential tremor, one vascular parkinsonism). All handwriting analysis was performed blind to clinical details. Subjective classification was made as: (1) micrographia, (2) normal, or (3) macrographia. In addition, a range of objective metrices were measured on standardized handwriting specimens. Subjective assessments found micrographia more frequently in PD than SWEDDs (p = 0.0352) and in akinetic-rigid than tremulous PD (p = 0.0259). Macrographia was predominantly seen in patients with dystonic tremor and not other diagnoses (p = 0.007). Micrographia had a mean sensitivity of 55 % and specificity of 84 % for distinguishing PD from SWEDDs and mean sensitivity of 90 % and specificity of 55 % for distinguishing akinetic-rigid PD from tremulous PD. Macrographia had a sensitivity of 26 % and specificity of 96 % for distinguishing DT from all other diagnoses. The best of the objective metrices increased sensitivity for the distinction of SWEDDs from PD with a reduction in specificity. We conclude that micrographia is more indicative of PD than SWEDDs and more characteristic of akinetic-rigid than tremulous PD. In addition, macrographia strongly suggests a diagnosis of dystonic tremor.
    Journal of Neurology 04/2012; · 3.58 Impact Factor
  • Practical Neurology 02/2012; 12(1):40-3.
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    ABSTRACT: Hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurological diseases, which typically present with progressive lower extremity weakness and spasticity causing progressive walking difficulties. Complicating neurological or extraneurological features may be present. We describe a 19-year-old male who was referred because of an action tremor of the hands; he later developed walking difficulties. Callosal atrophy was present on his cerebral magnetic resonance imaging scan, prompting genetic testing for SPG11, which revealed homozygous mutations. The clinical features, differential diagnosis and management of SPG11, the most common form of autosomal recessive complicated HSP with a thin corpus callosum are discussed.
    Tremor and other hyperkinetic movements (New York, N.Y.). 01/2012; 2.
  • Jeban Ganesalingam, Peter Bain
    Movement Disorders 09/2011; 26(12):2182. · 5.63 Impact Factor
  • Susanne A Schneider, Peter G Bain
    Movement Disorders 09/2011; 26(14):2462-3. · 5.63 Impact Factor
  • Leah Jones, Peter G Bain
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    ABSTRACT: Orthostatic tremor is characterised by a feeling of unsteadiness that is accompanied by a high frequency (13-18 Hz) tremor of the legs when standing, and which is relieved by sitting or walking. We describe a typical patient whose condition gradually progressed so that eventually he could no longer stand still. We discuss the clinical features, management and pathogenesis, and highlight the need for awareness of this condition because the diagnosis is often missed or delayed.
    Practical Neurology 08/2011; 11(4):240-3.
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    ABSTRACT: We investigated whether turning problems in Parkinson's disease may be the result of abnormal horizontal multisegmental angular coordination. Ten mildly affected patients and controls stood upright and voluntarily reoriented eyes and body to illuminated targets of eccentricities up to ±180 degrees. The effects of target location, visibility, and predictability on movement parameters were evaluated. Patients' latencies were normal. Control subjects foveated large eccentricity targets with a single gaze shift in approximately 30% of predictable trials. Patients rarely did so (10% of predictable trials) because of reduced head-in-space and trunk velocity. This resulted in massive foveation delays in patients-an average of half a second for displacements of 180 degrees. The covariation of eye, head, and trunk rotations was quantified statistically by means of principal components analysis. In both groups, the combined movement was initially stereotyped and two principal components accounted for nearly all data variance-the original three mechanical degrees of freedom (i.e., eye-head-trunk) are reduced to two kinematic degrees of freedom. However, in patients, the eye contributed more, and the head and trunk less, to the gaze shift than in control subjects. Although the eye-to-foot turning synergy is preserved in early-stage parkinsonism, quantitative differences are prominent, particularly a larger ocular (and smaller head-trunk) contribution in patients. Turning problems in Parkinson's disease do not result from inability to assemble multisegmental movements, as patients' ability to control numerous degrees of freedom is preserved. However, trunk bradykinesia reduces the frequency of single-step gaze shifts, thus prolonging target acquisition time. Preserved eye motion compensates for trunk slowness.
    Movement Disorders 06/2011; 26(12):2201-11. · 5.63 Impact Factor
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    ABSTRACT: Previous studies have compared the accuracy of spiral analysis in distinguishing essential tremor (ET) from PD. In this study, we have used this technique to distinguish cases of tremulous PD (TDPD) (N = 24) from tremulous parkinsonian subjects without evidence of dopaminergic deficit (N = 41). All patients were characterized on clinical and (123)I-N-ω-fluoro-propyl-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane ([(123)I] FP-CIT) SPECT scan data, which were concordant in every case. All analyses were carried out by observers blinded to the clinical details and supplied with just the spiral drawings, from which tremor severity (TS), 3-turn spiral diameter (3TD), and spiral density (SD) were measured. The spirals drawn by TDPD cases had significantly smaller 3TD (P = 0.029) and greater SD (P = 0.0082) than those with normal FP-CIT scans. There was no significant difference in the TS between the two groups (P = 0.11). The sensitivity and specificity of TS were 62.5% and 65.0%, 3TD were 75% and 56.7%, and SD were 30.4% and 82.5%, respectively, in predicting the correct classification. Further analyses combining these factors into pairs, showed that the respective sensitivities and specificities of (1) TS × 3TD were 75.0% and 40.0%, (2) TS/SD were 56% and 70.0%, and (3) 3TD/SD were 87.0% and 40.0%. There are significant differences in the 3TD and SD of spirals drawn by tremulous patients with normal versus abnormal FP-CIT scans. Spiral analysis may have some clinical value in helping to distinguish tremulous parkinsonian patients with normal presynaptic dopaminergic imaging from tremulous PD patients, providing results similar to those reported for expert movement disorder neurologists using standardized videotaped examinations.
    Movement Disorders 03/2011; 26(4):699-704. · 5.63 Impact Factor
  • Peter G Bain
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    ABSTRACT: Task-specific tremor is a form of action tremor that occurs only or mainly when a person is performing a specific skilled task. The most frequently encountered form of task-specific tremor is primary writing tremor (PWT). Currently, there is debate about whether PWT is a variant of essential tremor, writer's cramp (dystonia), a separate entity, or in some cases related to essential tremor and in others to dystonia. PWT typically occurs at a frequency of 5-7Hz and has been subdivided into to two types: Type A, task-induced tremor, and type B, positionally sensitive tremor. Temporary suppression of the tremor by alcohol is seen in about one-third of cases. There are no randomized controlled therapeutic studies involving patients with PWT, although anecdotal reports of beneficial responses to propranolol, primidone, anticholinergics, botulinum toxin treatment, and stereotactic surgery have been reported. Reciprocal inhibition of the H-reflex and intracortical excitability are normal in PWT, unlike writer's cramp. Hyperactivity in the cerebellar hemispheres has been demonstrated with positron emission tomography in PWT. Other task-specific tremors have been described but have not been studied in detail.
    Handbook of Clinical Neurology 01/2011; 100:711-8.
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    ABSTRACT: Five to fifteen per cent of de novo patients recruited for recent clinical trials of anti-parkinsonian drugs had no evidence of nigrostriatal dopamine denervation on functional imaging. These diagnostically challenging subjects without evidence of dopaminergic deficit (SWEDDs) had tremulous syndromes other than Parkinson's disease (PD). Our objective was to analyse the accuracy of spirography in distinguishing cases of tremor dominant PD from tremulous SWEDDs cases. Analyses were carried out by observers blinded to the clinical data and supplied with just spiral drawings, from which tremor severity, 3-turn spiral diameter and spiral density were measured. A spiral coefficient, averaged for the spirals drawn by each hand, was derived from these three indices. A cut off of <4 in the coefficient was taken to indicate PD. Of the 65 cases analysed, the data were felt to be of insufficient quality in 6. Of the remaining 59 cases, the sensitivity and specificity for differentiating tremor dominant PD from tremulous SWEDDs was 65.2% and 61.1% respectively. An analysis was also performed looking at the individual spiral components. This showed that the sensitivity and specificity for tremor severity were 62.5% and 74.3%, 3-turn diameter 75% and 77.8% and spiral density 28% and 67.3% respectively for predicting PD. The simple 3-turn spiral diameter has similar sensitivity and specificity for distinguishing PD from SWEDDs as reported for two blind PD experts assessing these patients from standardised videotapes.
    Journal of neurology, neurosurgery, and psychiatry 11/2010; 81(11):e60. · 4.87 Impact Factor
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    ABSTRACT: Why do some patients with Parkinson's disease develop risk-taking behaviour? We assessed responses to novelty and willingness to take risks in 29 patients with idiopathic Parkinson's disease (PD), compared to elderly controls and 14 PD patients with impulse control disorders (ICD). Participants were assessed on tasks designed to probe novelty processing and risk-taking behaviour. Akinetic-rigid PD patients, as well as those with ICD, were significantly quicker to respond to novel compared to nonnovel perceptually salient stimuli. By contrast tremor dominant PD patients and controls responded equally quickly to both types of stimuli. Faster reaction times to novel stimuli correlated with greater risk-taking on the Iowa Gambling Task for akinetic-rigid PD patients only. Importantly, there was no association between these measures and l-dopa equivalent dose. Instead, preserved structural integrity of mesolimbic regions (assessed with magnetisation transfer imaging) correlated with novelty-seeking in PD patients without ICD and increased risk-taking in the ICD patients. Akinetic-rigid patients tended to have higher levels of structural integrity here than tremor dominant patients. These results suggest that preservation of the mesolimbic dopaminergic system may play an important role in the development of ICD. Furthermore, our findings suggest akinetic-rigid patients may be more susceptible to developing these problems.
    Journal of neurology, neurosurgery, and psychiatry 11/2010; 81(11):e21. · 4.87 Impact Factor
  • P Bain, L Jones
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    ABSTRACT: Orthostatic tremor (OT) is a rarely reported condition defined as a subjective feeling of unsteadiness on standing, accompanied by a 13- to 18-Hz leg tremor that is relieved during sitting. There are 211 cases in the literature with a 2:1 female preponderance. The commonest presenting complaint being unsteadiness on standing. OT is described as causing tremor of the legs, trunk, and postural arm tremor. The effect of OT on spiral drawing and writing had not been studied. Clonazepam is considered the treatment of choice for OT, which is thought to respond poorly to alcohol. DaTSCAN imaging studies had shown conflicting results. Analysis of our 56 cases confirmed a female preponderance. The age at OT onset distribution had a single peak and was a decade later than essential tremor (ET), which is bimodal. Symptomatic leg tremor was ubiquitous, but OT affected the arms in 50%, head (20%), trunk (16%) and voice and tongue (both 7%) of cases. Tremulous writing and spiral drawings were present in 26.8% and 58.9% of cases respectively; 5.4% of OT cases reported a first degree relative with OT, 5.4% with PD and 10.7% with ET. OT responded to alcohol in 52%. The most effective therapy was primidone; beneficial in 26.7% of cases. Parkinsonian signs were common (37.5% reduced arm swing, 14.3% shuffling gait, 37.5% facial and 8.9% vocal impassivity and 4.3% upper limb rest tremor). DaTSCAN imaging was normal. Our data further characterises the clinical features and therapeutic response of OT.
    Journal of neurology, neurosurgery, and psychiatry 11/2010; 81(11):e22. · 4.87 Impact Factor
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    ABSTRACT: Patients suffering from Parkinson's disease (PD) will typically experience a range of motor and nonmotor symptoms during the course of their illness, each of which will affect a particular individual to varying degrees. However, patients' perceptions of troublesome symptoms often differ from the clinician's view, and these discrepancies can hamper effective management of PD. In this study, we have assessed 265 consecutive PD patients by asking them to rank their three most troublesome symptoms in the last 6 months, so to gain further insight from the impact of illness on patients' quality of life. Patients were divided into early (<6 years) and late PD groups (>/=6 years) from symptom onset. The division at 6 years was based on the mean time from symptom onset to the development of motor complications. In the early PD group, the 5 most prevalent complaints (ranked in descending order) are slowness, tremor, stiffness, pain, and loss of smell and/or taste. In the advanced PD group, fluctuating response to their medication (most common: wearing-off phenomenon followed by dyskinesia), mood changes, drooling, sleep problems (most common: middle and late night insomnia followed by daytime sleepiness), and tremor were the top 5. Our findings provide further evidence for the diversity of experience in PD and suggest that as the disease advances the most troublesome issues that patients perceive are the lack of response to medication and the nonmotor aspects of the disease, highlighting the importance of assessment and patient-centered management in the follow-up of these patients.
    Movement Disorders 08/2010; 25(11):1646-51. · 5.63 Impact Factor

Publication Stats

3k Citations
434.22 Total Impact Points

Institutions

  • 1998–2013
    • Imperial College London
      • • Department of Earth Science and Engineering
      • • Department of Medicine
      • • Faculty of Medicine
      • • Department of Electrical and Electronic Engineering
      London, ENG, United Kingdom
  • 2011–2012
    • Universität zu Lübeck
      Lübeck Hansestadt, Schleswig-Holstein, Germany
    • Nottingham University Hospitals NHS Trust
      • Department of Clinical Psychology and Neuropsychology
      Nottigham, England, United Kingdom
  • 2010
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 2001–2009
    • University of Oxford
      • Department of Physiology, Anatomy and Genetics
      Oxford, ENG, United Kingdom
  • 2008
    • University College London
      • Sobell Department of Motor Neuroscience and Movement Disorders
      London, ENG, United Kingdom
  • 2006
    • St George's, University of London
      Londinium, England, United Kingdom
  • 2005
    • Monash University (Australia)
      • Department of Surgery
      Melbourne, Victoria, Australia
  • 2002
    • Christian-Albrechts-Universität zu Kiel
      • Unit of Neurobiology
      Kiel, Schleswig-Holstein, Germany