Peter G Bain

Imperial College London, Londinium, England, United Kingdom

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Publications (128)541.72 Total impact

  • Movement Disorders 07/2015; 30(10). DOI:10.1002/mds.26344 · 5.68 Impact Factor
  • Peter G Bain ·

    Movement Disorders 07/2015; 30(10). DOI:10.1002/mds.26342 · 5.68 Impact Factor
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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; 124(3). DOI:10.1172/JCI71640 · 13.22 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; 19(12). DOI:10.1016/j.parkreldis.2013.08.011 · 3.97 Impact Factor
  • Barbara J Bain · Peter G Bain ·

    American Journal of Hematology 08/2013; 88(8). DOI:10.1002/ajh.23481 · 3.80 Impact Factor
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    ABSTRACT: The phenomenology of tremor is broad and its classification is complicated. Furthermore, the full range of tremor phenomenology with respect to specific neurological and neurodegenerative diseases has not been fully elaborated. This right-handed man had a chief complaint of jaw tremor, which began approximately 20 years prior to death at age 101 years. He had been diagnosed with essential tremor (ET) by a local doctor. His examination at age 100 years was notable for marked jaw tremor at rest in the absence of other clear features of parkinsonism, mild kinetic tremor of the hands and, in the last year of life, a score of 22/41 on a cognitive screen. A senior movement disorder neurologist raised doubt about the "ET" diagnosis. The history and videotaped examination were reviewed by three additional senior tremor experts, who raised a number of diagnostic possibilities. A complete postmortem examination was performed by a senior neuropathologist, and was notable for the presence of tufted astrocytes, AT8-labeled glial cytoplasmic inclusions, and globose neuronal tangles. These changes were widespread and definitive. A neuropathological diagnosis of progressive supranuclear palsy was assigned. This case presents with mixed and difficult to clinically classify tremor phenomenology and other neurological findings. The postmortem diagnosis was not predicted based on the clinical features, and it is possible that it does not account for all of the features. The case raises many interesting issues and provides a window into the complexity of the interpretation, nosology, and classification of tremor phenomenology.
    07/2013; 3.
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    BMC Neuroscience 07/2013; 14(1). DOI:10.1186/1471-2202-14-S1-P427 · 2.67 Impact Factor

  • Practical Neurology 05/2013; 13(4). DOI:10.1136/practneurol-2012-000490
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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; 80(20). DOI:10.1212/WNL.0b013e318292a31d · 8.29 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; 13(4). DOI:10.1136/practneurol-2012-000438
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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; 5(2). DOI:10.1039/c3mt20238k · 3.59 Impact Factor
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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.
    09/2012; 2.
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    ABSTRACT: The quadripolar electrodes used for deep brain stimulation are designed to give flexibility in contact configuration, optimize therapeutic effect, and minimize side-effects. A patient with essential tremor did not tolerate a bipolar setting due to the emergence of a pulling sensation in her face. However, when the polarity of the contacts was reversed, a 70% higher voltage was tolerated. Using an electric field model, we predicted that this effect was due to the proximity of the topmost contact to the internal capsule. Post-operative imaging supported this prediction. These results demonstrate how a multi-disciplinary approach allows us to optimize parameter settings.
    Neurocase 09/2012; 20(1):10-17. DOI:10.1080/13554794.2012.713495 · 1.12 Impact Factor
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    R E Roberts · P G Bain · B L Day · M Husain ·
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    ABSTRACT: Recent investigations into the neural basis of elite sporting performance have focused on whether cortical activity might characterize individual differences in ability. However, very little is understood about how changes in brain structure might contribute to individual differences in expert motor control. We compared the behavior and brain structure of healthy controls with a group of karate black belts, an expert group who are able to perform rapid, complex movements that require years of training. Using 3D motion tracking, we investigated whether the ability to control ballistic arm movements was associated with differences in white matter microstructure. We found that karate experts are better able than novices to coordinate the timing of inter-segmental joint velocities. Diffusion tensor imaging revealed significant differences between the groups in the microstructure of white matter in the superior cerebellar peduncles (SCPs) and primary motor cortex-brain regions that are critical to the voluntary control of movement. Motor coordination, the amount of experience, and the age at which training began were all associated with individual differences in white matter integrity in the cerebellum within the karate groups. These findings suggest a role for the white matter pathways of the SCPs in motor expertise.
    Cerebral Cortex 08/2012; 23(10). DOI:10.1093/cercor/bhs219 · 8.67 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. DOI:10.1111/j.1460-9568.2012.08086.x · 3.18 Impact Factor
  • N P S Bajaj · L Wang · V. K. Gontu · D G Grosset · P G Bain ·
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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; 259(11). DOI:10.1007/s00415-012-6495-5 · 3.38 Impact Factor
  • P. Bain · Y. Nigmatullina ·

    Journal of Neurology Neurosurgery & Psychiatry 02/2012; 83(3):e1-e1. DOI:10.1136/jnnp-2011-301993.27 · 6.81 Impact Factor
  • K. Muhammed · P. Bain ·

    Journal of Neurology Neurosurgery & Psychiatry 02/2012; 83(3):e1-e1. DOI:10.1136/jnnp-2011-301993.147 · 6.81 Impact Factor
  • Elisaveta Sokolov · Susanne A Schneider · Peter G Bain ·

    Practical Neurology 02/2012; 12(1):40-3. DOI:10.1136/practneurol-2011-000045

  • Parkinsonism & Related Disorders 01/2012; 18:S15–S16. DOI:10.1016/S1353-8020(11)70137-7 · 3.97 Impact Factor

Publication Stats

5k Citations
541.72 Total Impact Points


  • 1998-2014
    • Imperial College London
      • • Division of Brain Sciences
      • • Department of Earth Science and Engineering
      • • Faculty of Medicine
      • • Department of Electrical and Electronic Engineering
      Londinium, England, United Kingdom
  • 2010-2011
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 2001-2005
    • University of Oxford
      • Department of Physiology, Anatomy and Genetics
      Oxford, ENG, United Kingdom
  • 2002
    • Christian-Albrechts-Universität zu Kiel
      • Unit of Neurobiology
      Kiel, Schleswig-Holstein, Germany
  • 1993
    • University of London
      • The School of Pharmacy
      Londinium, England, United Kingdom