Hardev Pall

University of Birmingham, Birmingham, England, United Kingdom

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Publications (33)261.76 Total impact

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    ABSTRACT: sec> Objective Apathy has been reported as a possible adverse effect of deep brain stimulation of the subthalamic nucleus (STN-DBS). We investigated the prevalence and severity of apathy in 22 patients with Parkinson's disease (PD) who underwent STN-DBS and the effects on quality of life (QOL). Method All patients were assessed with the Lille Apathy Rating Scale (LARS), the Apathy Scale (AS) and the Parkinson's Disease Questionnaire and were compared to a control group of 38 patients on pharmacotherapy alone. The relationship between apathy and clinico-demographic variables was explored through correlation analysis. Results Apathy was reported by a similar proportion of patients in the two groups: 18.4% in the DBS group and 22.7% in the control group according to LARS ratings; 45.5% in the DBS group and 42.1% in the control group according to AS ratings. There was no significant difference in apathy or QOL ratings between the two groups. Significant correlations were observed between poorer QOL and degree of apathy, as measured by the LARS (p<0.001) and AS (p=0.021). PD-related disability also correlated with both apathy ratings (p><0.001 and p=0.017, respectively). Conclusion Our findings suggest that STN-DBS is not associated with changes in apathy in the PD population, as there was no difference in prevalence or severity of apathy between patients who had undergone STN-DBS and those on pharmacotherapy alone. More severe apathy was associated with a higher level of disability due to PD and worse QOL in PD but no other clinico-demographic characteristics. </sec
    Journal of Neurology Neurosurgery & Psychiatry 09/2015; 86(9). DOI:10.1136/jnnp-2015-311750.49 · 6.81 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):PA2296. DOI:10.1183/13993003.congress-2015.PA2296 · 7.64 Impact Factor
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    ABSTRACT: Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an exome-wide rare variant burden analysis of 363 index cases with familial ALS (FALS). The results revealed an excess of patient variants within TUBA4A, the gene encoding the Tubulin, Alpha 4A protein. Analysis of a further 272 FALS cases and 5,510 internal controls confirmed the overrepresentation as statistically significant and replicable. Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability. These results further emphasize the role of cytoskeletal defects in ALS and demonstrate the power of gene-based rare variant analyses in situations where causal genes cannot be identified through traditional segregation analysis.
    Neuron 10/2014; 84(2):324-31. DOI:10.1016/j.neuron.2014.09.027 · 15.05 Impact Factor
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    ABSTRACT: Myoclonus dystonia syndrome (MDS) is a young-onset movement disorder. A proportion of cases are due to mutations in the maternally imprinted SGCE gene. We assembled the largest cohort of MDS patients to date, and determined the frequency and type of SGCE mutations. The aim was to establish the motor phenotype in mutation carriers and utility of current diagnostic criteria. Eighty-nine probands with clinical features compatible with MDS were recruited from the UK and Ireland. Patients were phenotypically classified as "definite", "probable" or "possible" MDS according to previous guidelines. SGCE was analyzed using direct sequencing and copy number variant analysis. In those where no mutation was found, DYT1 (GAG deletion), GCH1, THAP1 and NKX2.1 genes were also sequenced. Nineteen (21.3 %) probands had an SGCE mutation. Three patterns of motor symptoms emerged: (1) early childhood onset upper body myoclonus and dystonia, (2) early childhood onset lower limb dystonia, progressing later to more pronounced myoclonus and upper body involvement, and (3) later childhood onset upper body myoclonus and dystonia with evident cervical involvement. Five probands had large contiguous gene deletions ranging from 0.7 to 2.3 Mb in size with distinctive clinical features, including short stature, joint laxity and microcephaly. Our data confirms that SGCE mutations are most commonly identified in MDS patients with (1) age at onset ≤10 years and (2) predominant upper body involvement of a pure myoclonus-dystonia. Cases with whole SGCE gene deletions had additional clinical characteristics, which are not always predicted by deletion size or gene involvement.
    Journal of Neurology 09/2014; 261(12). DOI:10.1007/s00415-014-7488-3 · 3.38 Impact Factor
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    Trials 11/2013; 14(Suppl 1):P114. DOI:10.1186/1745-6215-14-S1-P114 · 1.73 Impact Factor
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    ABSTRACT: Myoclonus Dystonia Syndrome (MDS) is a childhood onset, alcohol responsive movement disorder caused by mutations in the SGCE gene in a proportion of cases. Single family and case series have suggested co-morbid psychiatric disease but have not compared cases to a control group. To establish a cohort of MDS patients with SGCE mutations and a control group of alcohol-responsive tremor patients, and to systematically assess for psychiatric symptoms using standardised questionnaires. We collected 27 patients with SGCE mutations and 45 tremor control cases. The MINI International Neuropsychiatric Interview, PHQ-9, MADRS, YBOCS and AUDIT were used to assess psychiatric disease according to DSM-IV criteria. There was a higher rate of psychiatric disease in MDS patients compared to controls (p<0.05), specifically social phobia (p><0.05) and Obsessive-Compulsive disease (OCD) (p><0.001). Excess alcohol use was higher amongst the MDS group once cases ><18yrs were excluded. > Overall psychiatric disease is elevated amongst the MDS cohort compared to a control group with a chronic, socially stigmatizing disorder. OCD appears to be the greatest contributor to this effect and may reflect a pleiotropic function for the SGCE gene.
    Journal of neurology, neurosurgery, and psychiatry 09/2013; 84(9):e1. DOI:10.1136/jnnp-2013-306103.24 · 6.81 Impact Factor
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    ABSTRACT: Levodopa and other dopaminergic treatments have not had the expected effect on survival in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to improve motor function, motor fluctuations, health-related quality of life, and to reduce medication usage and drug-induced dyskinesia in patients with severe PD refractory to medical therapy. Little however, has been described on the impact of STN-DBS on the survival of these patients. We aim in this study to examine the impact of STN-DBS on the survival of patients with severe PD. Patients who were eligible for STN-DBS were given the choice of undergoing surgery or continuing on medical treatment. Those who exercised patient choice and preferred to continue with medical treatment formed a control population. All eligible patients seen in a 10-year period are included in this study. Our primary outcome measure is a difference in mortality between the two groups with a secondary measure of admission rates to residential (nursing home) care. 106 patients underwent STN-DBS, and 41 patients exercised patient choice and declined the procedure. The two groups were matched for age, gender, ethnicity, duration of disease, rates of pre-existing depression and Levodopa equivalent doses of anti-Parkinson's medications taken. Patients undergoing STN-DBS had significantly longer survival and were significantly less likely to be admitted to a residential care home than those managed purely medically. The statistical significance of these findings persisted after adjusting for potential confounding factors (survival: p=0.002, HR 0.29 (0.13 to 0.64) (residential care home admission: OR: 0.1 (95% CI 0.0 to 0.3; p<0.001). We show for the first time that there is a survival advantage of DBS surgery in advanced PD. The effect of potential bias factors is examined. The survival advantage may arise for several postulated reasons, ranging from improvement in axial functions, such as swallowing, to some as yet unrecognised benefit of reduction in dopaminergic medication. These findings are of great interest to both patients with PD and the health professionals considering the treatment options for patients with severe PD.
    Journal of neurology, neurosurgery, and psychiatry 07/2013; 85(1). DOI:10.1136/jnnp-2012-304715 · 6.81 Impact Factor
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    ABSTRACT: Our objective was to better understand UK-wide practice in managing sialorrhoea in motor neuron disease among specialist clinicians. We used a survey of neurologists in the UK with a special interest in motor neuron disease designed to establish clinicians' attitudes towards treatment options and resources for sialorrhoea management. Twenty-three clinicians replied, representing 21 centres. Sixteen centres were specialist MND Care Centres. Clinicians estimated seeing a total of 1391 newly diagnosed patients with MND in 2011. One hundred and ninety-three patients were described. Forty-two percent of patients reviewed in clinicians' last clinic had sialorrhoea and 46% of those with sialorrhoea had uncontrolled symptoms. Clinicians' preferred drugs were hyoscine patches, amitriptyline, carbocisteine and botulinum toxin. Botulinum toxin was used in 14 centres. Risk of dysphagia and staff skills were identified as the main barriers to botulinum toxin use. This survey suggests that there may be as many as 1700 patients with MND in the UK who have symptoms of sialorrhoea and that symptoms may be poorly controlled in nearly half. Treatment strategies varied, reflecting the lack of evidence based guidelines. The use of specialist treatments was influenced by local infrastructure. This study highlights the need for further work to develop evidence based guidance.
    05/2013; 14(7-8). DOI:10.3109/21678421.2013.790452
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    ABSTRACT: Myoclonus dystonia syndrome is a childhood onset hyperkinetic movement disorder characterized by predominant alcohol responsive upper body myoclonus and dystonia. A proportion of cases are due to mutations in the maternally imprinted SGCE gene. Previous studies have suggested that patients with SGCE mutations may have an increased rate of psychiatric disorders. We established a cohort of patients with myoclonus dystonia syndrome and SGCE mutations to determine the extent to which psychiatric disorders form part of the disease phenotype. In all, 89 patients with clinically suspected myoclonus dystonia syndrome were recruited from the UK and Ireland. SGCE was analysed using direct sequencing and for copy number variants. In those patients where no mutation was found TOR1A (GAG deletion), GCH1, THAP1 and NKX2-1 were also sequenced. SGCE mutation positive cases were systematically assessed using standardized psychiatric interviews and questionnaires and compared with a disability-matched control group of patients with alcohol responsive tremor. Nineteen (21%) probands had a SGCE mutation, five of which were novel. Recruitment of family members increased the affected SGCE mutation positive group to 27 of whom 21 (77%) had psychiatric symptoms. Obsessive-compulsive disorder was eight times more likely (P < 0.001) in mutation positive cases, compulsivity being the predominant feature (P < 0.001). Generalized anxiety disorder (P = 0.003) and alcohol dependence (P = 0.02) were five times more likely in mutation positive cases than tremor controls. SGCE mutations are associated with a specific psychiatric phenotype consisting of compulsivity, anxiety and alcoholism in addition to the characteristic motor phenotype. SGCE mutations are likely to have a pleiotropic effect in causing both motor and specific psychiatric symptoms.
    Brain 01/2013; 136(Pt 1):294-303. DOI:10.1093/brain/aws308 · 9.20 Impact Factor
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    ABSTRACT: Objective: Patients with Parkinson's disease (PD) can perform poorly on tasks involving theory of mind (ToM): the ability to reason about mental states. We investigated whether patients' ToM deficits were independent of executive dysfunction. Method: Experiment 1 aimed to establish that ToM deficits were present, and 2 following experiments manipulated the working memory (WM) demands of the ToM task. Results: In Experiment 1, 15 patients with PD performed significantly more poorly than controls on a false belief vignette task but not on a faux pas task. Errors were related to poor verbal fluency. In Experiment 2, 24 patients with PD made fewer errors on shorter false belief vignettes than the original FBT, and errors on the latter were related to WM impairment. In Experiment 3, the FBT was presented as a comic strip visible throughout questioning, reducing WM demands. Patients (n = 24) made memory errors but no false belief errors on the comic strip. They exhibited no verbal fluency or WM impairments, but did exhibit deficits on a black-and-white Stroop task. False belief errors were not correlated with executive performance. Conclusions: PD patients made very few ToM errors that were independent of errors on memory questions, so in this sample, ToM deficits per se appear unlikely. However, patients still made errors on ToM tasks when associated incidental WM demands were considerably reduced, highlighting the need for future investigations of ToM in PD to account for the role of more general cognitive restrictions exhibited by even some medicated, early stage patients.
    Neuropsychology 01/2013; 27(1):37-47. DOI:10.1037/a0031302 · 3.27 Impact Factor
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    ABSTRACT: Purpose Rare long-term neurological conditions (rLTNCs) may have significant impact on patients’ health-related quality of life (HRQL); however, evidence is sparse. We assessed HRQL and access to supportive care in patients with rLTNCs. Methods Survey of patients with rare rLTNCs (motor neurone disease, Huntington’s disease, cerebellar ataxia, progressive supranuclear palsy, multiple system atrophy, Charcot–Marie–Tooth disease and postpolio syndrome) to assess current access to health and social care, and HRQL using the Euroqol EQ-5D. Results A total of 266 participants with rLTNCs completed the survey. The HRQL of patients is substantially reduced compared to the general population. Many patients reported pain, were anxious or depressed and experienced problems with mobility, self-care and usual activities (mean EQ-5D index scores ranged from 0.2 to 0.44). Although some patients have accessed rehabilitative services, results suggest care coordination could be improved. Conclusions Rare long-term neurological conditions have a significant impact on HRQL. Many patients with rLTNCs do not seem to be accessing the level of health and social care services that could improve their HRQL.
    Quality of Life Research 09/2012; 22(6). DOI:10.1007/s11136-012-0269-5 · 2.49 Impact Factor
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    ABSTRACT: A massive hexanucleotide repeat expansion mutation (HREM) in C9ORF72 has recently been linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we describe the frequency, origin and stability of this mutation in ALS+/-FTD from five European cohorts (total n=1347). Single-nucleotide polymorphisms defining the risk haplotype in linked kindreds were genotyped in cases (n=434) and controls (n=856). Haplotypes were analysed using PLINK and aged using DMLE+. In a London clinic cohort, the HREM was the most common mutation in familial ALS+/-FTD: C9ORF72 29/112 (26%), SOD1 27/112 (24%), TARDBP 1/112 (1%) and FUS 4/112 (4%) and detected in 13/216 (6%) of unselected sporadic ALS cases but was rare in controls (3/856, 0.3%). HREM prevalence was high for familial ALS+/-FTD throughout Europe: Belgium 19/22 (86%), Sweden 30/41 (73%), the Netherlands 10/27 (37%) and Italy 4/20 (20%). The HREM did not affect the age at onset or survival of ALS patients. Haplotype analysis identified a common founder in all 137 HREM carriers that arose around 6300 years ago. The haplotype from which the HREM arose is intrinsically unstable with an increased number of repeats (average 8, compared with 2 for controls, P<10(-8)). We conclude that the HREM has a single founder and is the most common mutation in familial and sporadic ALS in Europe.European Journal of Human Genetics advance online publication, 13 June 2012; doi:10.1038/ejhg.2012.98.
    European journal of human genetics: EJHG 06/2012; 21(1). DOI:10.1038/ejhg.2012.98 · 4.35 Impact Factor
  • Hajar Alobaidi · Hardev Pall ·
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    ABSTRACT: Objectives: The pharmacotherapy of Parkinson's disease (PD) is often challenging as clinicians have to find a favourable balance between the efficacy on motor symptoms and side effect profiles of different dopaminergic medications. We aimed to assess the available evidence on the role of dopamine agonist monotherapy as an alternative to Levodopa in the treatment of motor symptoms of PD, along with the role of dopamine antagonists in the treatment of PD-related psychosis. Methods: We performed a systematic literature review using the databases MEDLINE, EMBASE, PsycINFO and the Cochrane Library Central register of controlled trials. Two searches were performed, 'Search 1' extracting trials on dopamine agonists, and 'Search 2' on atypical antipsychotics. Eligible studies were Double-blind Randomised Controlled Trials (RCTs) using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Brief Psychiatric Rating Scale (BPRS) as outcome measures for Search 1 and 2, respectively. Results: 16 relevant RCTs were extracted from the search results. Overall, dopamine agonists were shown to significantly improve UPDRS scores, with a mean percentage improvement of 14.4% compared to -1.9% in the control arm (P value < 0.05). However, their side effect profile illustrated they were associated with twice the incidence of psychotic symptoms in comparison to the controls. The results on the efficacy of atypical antipsychotics for the treatment of PD-related psychosis were not significant. Conclusions: This evidence-based review confirmed that dopamine agonists can be an effective and safe treatment as monotherapy in PD, however psychotic symptoms remain a significant side effect. Atypical antipsychotics may not be relied upon for the correction of these symptoms due to inconsistent results about their efficacy.
    Behavioural neurology 05/2012; 26(4). DOI:10.3233/BEN-2012-120265 · 1.45 Impact Factor
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    ABSTRACT: While some cases of familial ALS can be entirely attributed to known inherited variation, the majority (∼ 90%) are sporadic, where the cause(s) are not entirely understood. Both genetic and environmental factors may contribute to susceptibility. Mitochondrial damage, a common feature of neurodegenerative disease, is observed in most patients and inherited polymorphism in the mitochondrial genome has been suggested as a contributing factor. We used an economic and efficient method to test whether such involvement is probable. We genotyped 22 mtDNA coding region SNPs and sequenced the mtDNA hypervariable region 1 to determine the position of each mitochondrial genome within the genealogy of mitochondrial haplotypes in samples of ALS patients (n = 700) and controls (n = 462) from two European populations. We compared haplotype and haplogroup distribution in cases and controls drawn from the same populations. No statistical difference was observed between cases and controls at either the haplogroup or haplotype level (p = ≥  0.2). In conclusion, it is unlikely that common, shared genetic variants in the mitochondrial genome contribute substantially to ALS. Combining the data with other studies will allow meta-analysis to look for variants with modest effect sizes. The sequencing of complete mitochondrial genomes will be required to assess the role of rare mutations.
    Amyotrophic Lateral Sclerosis 03/2012; 13(4):341-6. DOI:10.3109/17482968.2012.654394 · 2.37 Impact Factor
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    ABSTRACT: We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We screened 4448 patients diagnosed with ALS (El Escorial criteria) and 1425 patients with FTD (Lund-Manchester criteria) from 17 regions worldwide for the GGGGCC hexanucleotide expansion using a repeat-primed PCR assay. We assessed familial disease status on the basis of self-reported family history of similar neurodegenerative diseases at the time of sample collection. We compared haplotype data for 262 patients carrying the expansion with the known Finnish founder risk haplotype across the chromosomal locus. We calculated age-related penetrance using the Kaplan-Meier method with data for 603 individuals with the expansion. In patients with sporadic ALS, we identified the repeat expansion in 236 (7·0%) of 3377 white individuals from the USA, Europe, and Australia, two (4·1%) of 49 black individuals from the USA, and six (8·3%) of 72 Hispanic individuals from the USA. The mutation was present in 217 (39·3%) of 552 white individuals with familial ALS from Europe and the USA. 59 (6·0%) of 981 white Europeans with sporadic FTD had the mutation, as did 99 (24·8%) of 400 white Europeans with familial FTD. Data for other ethnic groups were sparse, but we identified one Asian patient with familial ALS (from 20 assessed) and two with familial FTD (from three assessed) who carried the mutation. The mutation was not carried by the three Native Americans or 360 patients from Asia or the Pacific Islands with sporadic ALS who were tested, or by 41 Asian patients with sporadic FTD. All patients with the repeat expansion had (partly or fully) the founder haplotype, suggesting a one-off expansion occurring about 1500 years ago. The pathogenic expansion was non-penetrant in individuals younger than 35 years, 50% penetrant by 58 years, and almost fully penetrant by 80 years. A common Mendelian genetic lesion in C9orf72 is implicated in many cases of sporadic and familial ALS and FTD. Testing for this pathogenic expansion should be considered in the management and genetic counselling of patients with these fatal neurodegenerative diseases. Full funding sources listed at end of paper (see Acknowledgments).
    The Lancet Neurology 03/2012; 11(4):323-30. DOI:10.1016/S1474-4422(12)70043-1 · 21.90 Impact Factor

  • Journal of Neurology Neurosurgery & Psychiatry 02/2012; 83(3):e1-e1. DOI:10.1136/jnnp-2011-301993.29 · 6.81 Impact Factor
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    ABSTRACT: The authors analyze long-term outcome in a substantial number of patients who underwent subthalamic nucleus (STN) deep brain stimulation (DBS) surgery under general anesthesia. Eighty-two patients underwent bilateral placement of DBS electrodes under general anesthesia for advanced Parkinson disease; the STN was the target in all cases. All patients underwent intraoperative microelectrode recording of the STN. No intraoperative macrostimulation was performed. Unified Parkinson's Disease Rating Scale (UPDRS) data were recorded in 28 patients. Assessment of outcome was performed using the UPDRS (in 28 cases), the electrophysiological recordings (in all 82 cases), medication reduction (in 78 cases), and complications (in 82 cases). There was improvement in UPDRS scores across all measures following surgery. The total UPDRS score, off medication, improved from 68.78 (geometrical mean, 95% CI 61.76-76.60) preoperatively to 45.89 (geometrical mean, 95% CI 34.86-60.41) at 1 year postoperatively (p = 0.003, data available in 26 patients). Improvements were obtained in UPDRS Part II (Activities of Daily Living) off medication (p = 0.001) and also UPDRS Part III (Motor Examination) off medication (p < 0.001). Results for the on-medication and on-stimulation states also showed a statistically significant improvement for UPDRS Part III (p = 0.047). Good microelectrode recording of the STN was obtained under general anesthesia; the median first-track length was 4.0 mm, and the median number of tracks passed per patient was 3.0. The median reduction in levodopa medication was 58.1% (interquartile range 42.9%-73.3%). One patient had an intracerebral hemorrhage in the track of 1 electrode but did not require surgical evacuation. One patient had generalized convulsive seizures 24 hours postoperatively and was intubated for seizure control. Unified Parkinson's Disease Rating Scale scores were obtained in 26 patients at 1 year, 28 patients at 3 years, 17 at 5 years, and 7 at 7 years postoperatively. Up to 7 years postoperatively, there was sustained improvement in the total UPDRS score. The results in these patients showed minimal deterioration in the motor section of the UPDRS over time, up to 7 years following the operation. The authors found no evidence that the UPDRS Part II scores changed significantly over the period of 1-7 years after surgery (p = 0.671, comparison of mean scores at 1 and 7 years using generalized estimating equations). Long-term outcomes confirm that it is both safe and effective to perform STN DBS under general anesthesia. As part of patient choice, this option should be offered to all DBS candidates with advanced Parkinson disease to enable more of these patients to undergo this beneficial surgery.
    Journal of Neurosurgery 01/2012; 116(1):107-13. DOI:10.3171/2011.7.JNS11319 · 3.74 Impact Factor
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    ABSTRACT: Recent debate suggests Huntington's disease (HD) may be more prevalent than previously reported. In addition, relatively little is known about current disease management. This study aims to provide epidemiological data and describe the pharmacological management of HD in the United Kingdom. A primary care research database was accessed to identify incident and prevalent HD cases between January 1, 2004, and December 31, 2008. Patients with Read codes denoting a definite diagnosis or possible diagnosis, and undiagnosed patients with a positive family history were identified. A subset of patients with a definite diagnosis and prescribed medication indicating symptom onset was also identified. Epidemiological data were estimated. Pharmacological prescriptions to HD patients from 2004 to 2008 were identified, and prescription frequencies were grouped according to the British National Formulary categories. HD incidence estimates ranged from 0.44 to 0.78 per 100,000 person-years, and HD prevalence ranged from 5.96 to 6.54 per 100,000 of the population. Forty-four percent of pharmacological prescriptions targeted the central nervous system. Nearly half of the HD patients were prescribed antidepressants, and over 40% were prescribed analgesics. Although prevalence estimates fell short of figures suggested in recent debate, it is feasible that the true prevalence may be much higher than previously reported. Pharmacological management appears to rely heavily on central nervous system drugs and nutrition support. Many of these drugs are prescribed to HD patients for reasons other than the medication's primary use. Further work is required to evaluate the impact of alternative management strategies, such as therapist intervention, counselling, and organisation support, on the patients' quality of life.
    Neuroepidemiology 12/2011; 37(3-4):216-21. DOI:10.1159/000331912 · 2.56 Impact Factor
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    ABSTRACT: Subthalamic deep brain stimulation (STN DBS) for Parkinson's disease typically enables a 50% reduction in dopaminergic medication postoperatively. This reduction in medication is accompanied by a 60% reduction in dyskinesia and a reduction in off periods. However, there remains a subgroup of patients who have disabling dyskinesias despite optimisation of drug and stimulator setting. Amantadine is sometimes used for the medical management of drug-induced dyskinesias in Parkinson's disease. Its use in dyskinesias after DBS has not been formally assessed.We report a series of 8 cases who had bilateral STN DBS. These patients had similar characteristics to our local database of patients who have had DBS. However, these patients had disabling bradykinesia and/or dyskinesias despite attempts at optimisation of stimulator settings and dopaminergic medication. The addition of amantadine led to clear improvements in dsykinesias and/or mobility, without the need to increase the total dose of dopaminergic medication. Stopping amantadine caused worsening of symptoms.This case series suggests amantadine is an important additional medication in the small group of patients whose disease has not been stabilised after DBS. The outflow of the STN includes a glutamatergic pathway. The glutamate receptor blocking properties of amantadine provide a possible mechanism for the observed benefit.We plan to extend the results of this case series to include objective scoring in subsequent patients.
    Journal of Neurology Neurosurgery & Psychiatry 08/2011; 82(9). DOI:10.1136/jnnp-2011-300645.7 · 6.81 Impact Factor
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    ABSTRACT: Hope has been identified as a key attribute required for neurological rehabilitation. Expressions of hope form the basis for patient narratives within this context. The purpose of this study was to use patient's experience of hope as a way of understanding narrative types. This study looks at three different neurological conditions: spinal cord injury, stroke and multiple sclerosis. Using a meta-ethnographical method, eight narrative macrostructures were identified by three groups of hope: (1) hope as a dichotomy, (2) hope as a paradox and (3) transcendence. The discussion provides further details of these groups and establishes how therapeutic emplotment may influence and guide narratives within neurological rehabilitation.
    Health Psychology Review 04/2011; 1–25(2-iFirst). DOI:10.1080/17437199.2011.568856 · 6.75 Impact Factor

Publication Stats

1k Citations
261.76 Total Impact Points


  • 2006-2014
    • University of Birmingham
      • • School of Clinical and Experimental Medicine
      • • Institute for Biomedical Research
      Birmingham, England, United Kingdom
  • 2012-2013
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 2010
    • The Queen Elizabeth Hospital
      Tarndarnya, South Australia, Australia