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1.  In the psychiatrist's chair: how neurologists understand conversion disorder 
Brain  2009;132(10):2889-2896.
Conversion disorder (‘hysteria’) was largely considered to be a neurological problem in the 19th century, but without a neuropathological explanation it was commonly assimilated with malingering. The theories of Janet and Freud transformed hysteria into a psychiatric condition, but as such models decline in popularity and a neurobiology of conversion has yet to be found, today's neurologists once again face a disorder without an accepted model. This article explores how today's neurologists understand conversion through in-depth interviews with 22 neurology consultants. The neurologists endorsed psychological models but did not understand their patients in such terms. Rather, they distinguished conversion from other unexplained conditions clinically by its severity and inconsistency. While many did not see this as clearly distinct from feigning, they did not feel that this was their problem to resolve. They saw themselves as ‘agnostic’ regarding non-neuropathological explanations. However, since neurologists are in some ways more expert in conversion than psychiatrists, their continuing support for the deception model is important, and begs an explanation. One reason for the model's persistence may be that it is employed as a diagnostic device, used to differentiate between those unexplained symptoms that could, in principle, have a medical explanation and those that could not.
doi:10.1093/brain/awp060
PMCID: PMC2759333  PMID: 19321463
conversion disorder; hysteria; malingering; deception; factitious disorder
2.  Neurologists' understanding and management of conversion disorder 
Background
Conversion disorder is largely managed by neurologists, for whom it presents great challenges to understanding and management. This study aimed to quantify these challenges, examining how neurologists understand conversion disorder, and what they tell their patients.
Methods
A postal survey of all consultant neurologists in the UK registered with the Association of British Neurologists.
Results
349 of 591 practising consultant neurologists completed the survey. They saw conversion disorder commonly. While they endorsed psychological models for conversion, they diagnosed it according to features of the clinical presentation, most importantly inconsistency and abnormal illness behaviour. Most of the respondents saw feigning as entangled with conversion disorder, with a minority seeing one as a variant of the other. They were quite willing to discuss psychological factors as long as the patient was receptive but were generally unwilling to discuss feigning even though they saw it as their responsibility. Those who favoured models in terms of feigning were older, while younger, female neurologists preferred psychological models, believed conversion would one day be understood neurologically and found communicating with their conversion patients easier than it had been in the past.
Discussion
Neurologists accept psychological models for conversion disorder but do not employ them in their diagnosis; they do not see conversion as clearly different from feigning. This may be changing as younger, female neurologists endorse psychological views more clearly and find it easier to discuss with their patients.
doi:10.1136/jnnp.2010.233114
PMCID: PMC3191819  PMID: 21325661
3.  Slater revisited: 6 year follow up study of patients with medically unexplained motor symptoms 
BMJ : British Medical Journal  1998;316(7131):582-586.
Objective: To investigate psychiatric and neurological morbidity, diagnostic stability, and indicators of prognosis in patients previously identified as having medically unexplained motor symptoms.
Design: Follow up study.
Setting: National Hospital for Neurology and Neurosurgery, London—a secondary and tertiary referral hospital for neurological disorders.
Subjects: 73 patients with medically unexplained motor symptoms admitted consecutively in 1989-91. 35 (48%) patients had absence of motor function (for example, hemiplegia) and 38 (52%) had abnormal motor activity (for example, tremor, dystonia, or ataxia).
Main outcome measures: Neurological clinical diagnosis at face to face reassessment by a neurologist and a psychiatric diagnosis after a standardised assessment interview—the schedule for affective disorders and schizophrenia—conducted by a psychiatrist.
Results: Good follow up data were available for 64 subjects (88%). Only three subjects had new organic neurological disorders at follow up that fully or partly explained their previous symptoms. 44/59 (75%) subjects had had psychiatric disorders; in 33 (75%) patients, the psychiatric diagnosis coincided with their unexplained motor symptoms. 31/59 (45%) patients had a personality disorder. Three subjects had developed new psychiatric illnesses at follow up, but in only one did the diagnosis account for the previous motor symptoms. Resolution of physical symptoms was associated with short length of symptoms, comorbid psychiatric disorder, and a change in marital status during follow up.
Conclusions: Unlike Slater’s study of 1965, a low incidence of physical or psychiatric diagnoses which explained these patients’ symptoms or disability was found. However, a high level of psychiatric comorbidity existed.
Key messages Motor symptoms that remain unexplained medically despite thorough investigation are a common clinical problem, but the emergence of a subsequent organic explanation for these symptoms is rare The prevalence of coexistent affective and anxiety disorders is high and many patients also have a personality disorder Patients with a shorter duration of symptoms and coexistent anxiety or depression are likely to do better at follow up Reinvestigation of these patients is both expensive and potentially dangerous and should be avoided where no clear clinical indication exists
PMCID: PMC28460  PMID: 9518908
4.  The 12 year prognosis of unilateral functional weakness and sensory disturbance 
Background: Although the symptoms of unilateral "medically unexplained" or "functional" weakness and sensory disturbance present commonly to neurologists, little is known about their long term prognosis.
Objective: To determine the long term outcome of functional weakness and sensory disturbance.
Patients: A previously assembled cohort of 60 patients seen as inpatients by consultant neurologists in Edinburgh between 1985 and 1992 and diagnosed as having unilateral functional weakness or sensory disturbance.
Methods: Current symptoms, disability, and distress were assessed by postal questionnaire to the patients and their family doctors.
Results: Follow up data relating to mortality were obtained in 56 patients (93%) and to current diagnosis in 48 patients (80%). Patient questionnaire data were obtained in 42 patients (70%). The median duration of follow up was 12.5 years (range 9 to 16). Thirty five of the 42 patients (83%) still reported weakness or sensory symptoms, and the majority reported limitation of physical function, distress, and multiple other somatic symptoms. Twenty nine per cent had taken medical retirement. An examination of baseline predictors indicated that patients who had sensory symptoms had better functioning at follow up than those who had weakness. Only one patient had developed a neurological disorder which, in hindsight, explained the original presentation. Another patient had died of unrelated causes.
Conclusions: Many patients assessed by neurologists with unilateral functional weakness and sensory symptoms as inpatients remain symptomatic, distressed, and disabled as long as 12 years after the original diagnosis. These symptoms are only rarely explained by the subsequent development of a recognisable neurological disorder in the long term.
doi:10.1136/jnnp.74.5.591
PMCID: PMC1738446  PMID: 12700300
5.  Antibody to Aquaporin 4 in the Diagnosis of Neuromyelitis Optica 
PLoS Medicine  2007;4(4):e133.
Background
Neuromyelitis optica (NMO) is a demyelinating disease of the central nervous system (CNS) of putative autoimmune aetiology. Early discrimination between multiple sclerosis (MS) and NMO is important, as optimum treatment for both diseases may differ considerably. Recently, using indirect immunofluorescence analysis, a new serum autoantibody (NMO-IgG) has been detected in NMO patients. The binding sites of this autoantibody were reported to colocalize with aquaporin 4 (AQP4) water channels. Thus we hypothesized that AQP4 antibodies in fact characterize NMO patients.
Methods and Findings
Based on these observations we cloned human water channel AQP4, expressed the protein in a eukaryotic transcription/translation system, and employed the recombinant AQP4 to establish a new radioimmunoprecipitation assay (RIPA). Indeed, application of this RIPA showed that antibodies against AQP4 exist in the majority of patients with NMO (n = 37; 21 positive) as well as in patients with isolated longitudinally extensive transverse myelitis (n = 6; six positive), corresponding to a sensitivity of 62.8% and a specificity of 98.3%. By contrast, AQP4 antibodies were virtually absent in 291 other participants, which included patients with MS (n = 144; four positive), patients with other inflammatory and noninflammatory neurological diseases (n = 73; one positive), patients with systemic autoimmune diseases (n = 45; 0 positive), and healthy participants (n = 29; 0 positive).
Conclusions
In the largest series reported so far to our knowledge, we quantified AQP4 antibodies in patients with NMO versus various other diseases, and showed that the aquaporin 4 water channel is a target antigen in a majority of patients with NMO. The newly developed assay represents a highly specific, observer-independent, and easily reproducible detection method facilitating clinically relevant discrimination between NMO, MS, and other inflammatory diseases.
A newly developed method to detect antibodies to the aquaporin 4 water channel can help discriminate between neuromyelitis optica, multiple sclerosis, and other inflammatory diseases.
Editors' Summary
Background.
Neuromyelitis optica (NMO or Devic syndrome) is a rare disease in which the immune system destroys the myelin (fatty material that insulates nerve fibers so that the body and the brain can communicate using electrical messages) in the optic nerve and spinal cord. Myelin destruction (demyelination) in these parts of the central nervous system (CNS) causes pain and swelling (inflammation) of the optic nerve (optic neuritis) and spinal cord (myelitis). The resultant disruption of communication along these nerves means that patients with NMO experience temporary or permanent blindness in one or both eyes that is preceded or followed by limb weakness or paralysis and loss of bladder and bowel control. These two sets of symptoms can occur many months apart and may happen once during a person's lifetime or recur at intervals. There is no cure for NMO, but corticosteroids or plasmapheresis reduce inflammation during acute attacks and, because NMO is an autoimmune disease (one in which the immune system attacks the body's own tissues instead of foreign organisms), long-term immunosuppression may prevent further attacks.
Why Was This Study Done?
There are many inflammatory/demyelinating diseases of the CNS with clinical symptoms similar to those of NMO. It is particularly hard to distinguish between NMO and multiple sclerosis, an autoimmune disease that involves widespread demyelination. Neurologists need to make a correct diagnosis before starting any treatment and usually use clinical examination and magnetic resonance imaging (to detect sites of inflammation) to help them in this task. Recently, however, a biomarker for NMO was identified. Many patients with NMO make autoantibodies (proteins that recognize a component of a person's own tissues) called NMO-IgGs. These recognize aquaporin 4 (AQP4), a protein that allows water to move through cell membranes. It is not known how often patients with NMO or other demyelinating diseases make antibodies to AQP4, so it is unclear whether testing for these antibodies would help in the diagnosis of NMO. In this study, the researchers have developed a new assay for antibodies to AQP4 and then quantified the antibodies in patients with NMO and other demyelinating diseases.
What Did the Researchers Do and Find?
The researchers made radioactively labeled AQP4 in a test tube, then incubated samples of this with serum (the liquid portion of blood), added small beads coated with protein A (a bacterial protein that binds to antibodies) and allowed the beads to settle. The amount of radioactivity attached to the beads indicates the amount of antibody to AQP4 in the original serum. The researchers used this radioimmunoprecipitation assay to measure antibodies to AQP4 in sera from 37 patients with NMO and from six with another neurological condition, longitudinally extensive transverse myelitis (LETM), which is characterized by large demyelinated lesions across the width of the spinal cord but no optic neuritis; these patients often develop NMO. They also measured antibodies to AQP4 in the sera of nearly 300 other people including patients with multiple sclerosis, other neurological conditions, various autoimmune diseases, and healthy individuals. Nearly two-thirds of the patients with NMO and all those with LETM made antibodies against AQP4; very few of the other study participants made these antibodies. In particular, only four of the 144 patients with multiple sclerosis made AQP4 antibodies.
What Do These Findings Mean?
These findings indicate that testing for antibodies to AQP4 could help neurologists distinguish between NMO and multiple sclerosis and between NMO and other demyelinating diseases of the CNS. In addition, the new radioimmunoprecipitation assay provides a standardized, high-throughput way to quantitatively test for these antibodies, whereas the indirect immune fluorescence assay for measurement of unspecific NMO-IgG is observer-dependent and nonquantitative. Although these findings need to be confirmed in more patients and the assay's reliability demonstrated in different settings, the measurement of antibodies to AQP4 by radioimmunoprecipitation may become a standard part of the differential diagnosis of NMO. Additional research will determine whether AQP4 is the only protein targeted by autoantibodies in NMO and whether this targeting is a critical part of the disease process.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040133.
US National Institute of Neurological Disorders and Stroke has information for patients who have neuromyelitis optica, transverse myelitis, and multiple sclerosis
The Transverse Myelitis Association offers information and useful links for patients and their carers about transverse myelitis and neuromyelitis optica (in several languages, including English and Spanish)
Mayo Clinic information for patients on Devic's syndrome
Medline Plus encyclopedia pages discuss autoimmune disorders (in English and Spanish)
A brief overview of aquaporins is available from the University of Miami
The American MS Society has information on MS
doi:10.1371/journal.pmed.0040133
PMCID: PMC1852124  PMID: 17439296
6.  Functional symptoms in neurology: questions and answers 
Between 10 and 30% of patients seen by neurologists have symptoms for which there is no current pathophysiological explanation. The objective of this review is to answer questions many neurologists have about disorders characterised by unexplained symptoms (functional disorders) by conducting a multidisciplinary review based on published reports and clinical experience. Current concepts explain functional symptoms as resulting from auto-suggestion, innate coping styles, disorders of volition or attention. Predisposing, precipitating, and perpetuating aetiological factors can be identified and contribute to a therapeutic formulation. The sympathetic communication of the diagnosis by the neurologist is important and all patients should be screened for psychiatric or psychological symptoms because up to two thirds have symptomatic psychiatric comorbidity. Treatment programmes are likely to be most successful if there is close collaboration between neurologists, (liaison) psychiatrists, psychologists, and general practitioners. Long term, symptoms persist in over 50% of patients and many patients remain dependent on financial help from the government. Neurologists can acquire the skills needed to engage patients in psychological treatment but would benefit from closer working relationships with liaison psychiatry or psychology.
doi:10.1136/jnnp.2004.048280
PMCID: PMC1739564  PMID: 15716517
7.  Neurological disease, emotional disorder, and disability: they are related: a study of 300 consecutive new referrals to a neurology outpatient department 
OBJECTIVES—To determine the prevalence of anxiety and depressive disorders in patients referred to general neurology outpatient clinics, to compare disability and number of somatic symptoms in patients with and without emotional disorder, the relation to neurological disease, and assess the need for psychiatric treatment as perceived by patients and doctors.
METHODS—A prospective cohort study set in a regional neurology service in Edinburgh, Scotland. The subjects were 300 newly referred consecutive outpatients who were assessed for DSM IV anxiety and depressive disorders (PRIME-MD, and HAD), health status, and disability (SF-36), and patients', GPs' and neurologists' ratings of the need for patient to receive psychiatric or psychological treatment.
RESULTS—Of 300 new patients, 140 (47%) met criteria for one or more DSM IV anxiety or depressive diagnosis. Major depression was the most common (27%). A comparison of patients with and without emotional disorder showed that physical function, physical role functioning, bodily pain, and social functioning were worse in patients with emotional disorders (p<0.0005). The median number of somatic symptoms was greater in patients with emotional disorders (p<0.0005). These differences were independent of the presence of neurological disease. Few patients wished to receive psychiatric or psychological treatments. Both general practitioners and neurologists were more likely to recommend psychiatric treatment when the patients' symptoms were medically unexplained.
CONCLUSIONS—Almost half of new referrals to general neurology clinics met criteria for a DSM IV psychiatric diagnosis. These patients were more disabled, and had more somatic symptoms. They expressed little enthusiasm for receiving psychiatric treatment.


doi:10.1136/jnnp.68.2.202
PMCID: PMC1736760  PMID: 10644788
8.  Trends in Resource Utilization by Children with Neurological Impairment in the United States Inpatient Health Care System: A Repeat Cross-Sectional Study 
PLoS Medicine  2012;9(1):e1001158.
Jay Berry and colleagues report findings from an analysis of hospitalization data in the US, examining the proportion of inpatient resources attributable to care for children with neurological impairment.
Background
Care advances in the United States (US) have led to improved survival of children with neurological impairment (NI). Children with NI may account for an increasing proportion of hospital resources. However, this assumption has not been tested at a national level.
Methods and Findings
We conducted a study of 25,747,016 US hospitalizations of children recorded in the Kids' Inpatient Database (years 1997, 2000, 2003, and 2006). Children with NI were identified with International Classification of Diseases, 9th Revision, Clinical Modification diagnoses resulting in functional and/or intellectual impairment. We assessed trends in inpatient resource utilization for children with NI with a Mantel-Haenszel chi-square test using all 4 y of data combined. Across the 4 y combined, children with NI accounted for 5.2% (1,338,590) of all hospitalizations. Epilepsy (52.2% [n = 538,978]) and cerebral palsy (15.9% [n = 164,665]) were the most prevalent NI diagnoses. The proportion of hospitalizations attributable to children with NI did not change significantly (p = 0.32) over time. In 2006, children with NI accounted for 5.3% (n = 345,621) of all hospitalizations, 13.9% (n = 3.4 million) of bed days, and 21.6% (US$17.7 billion) of all hospital charges within all hospitals. Over time, the proportion of hospitalizations attributable to children with NI decreased within non-children's hospitals (3.0% [n = 146,324] in 1997 to 2.5% [n = 113,097] in 2006, p<.001) and increased within children's hospitals (11.7% [n = 179,324] in 1997 to 13.5% [n = 209,708] in 2006, p<0.001). In 2006, children with NI accounted for 24.7% (2.1 million) of bed days and 29.0% (US$12.0 billion) of hospital charges within children's hospitals.
Conclusions
Children with NI account for a substantial proportion of inpatient resources utilized in the US. Their impact is growing within children's hospitals. We must ensure that the current health care system is staffed, educated, and equipped to serve this growing segment of vulnerable children.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Disorders of the central and peripheral nervous system, often referred to as neurological impairments, are common in infants and children and can cause functional or intellectual disability. There are many causes of neurological impairments, including birth trauma, congenital abnormalities, structural defects, infections, tumors, blood flow disruption, genetic and metabolic conditions, and toxins. Symptoms can be progressive or static and vary widely depending on the condition. For example, developmental delay, changes in activity—often due to muscle wasting—and seizures may be common symptoms of neurological conditions in children. In many countries, extremely premature babies, and children with conditions such as spina bifida and muscular dystrophy, now receive better care than they used to, and may survive longer. However, although such children may have long-term care needs, they may receive crisis-driven, uncoordinated care, even in high-income countries.
Why Was This Study Done?
It is not well understood what proportion of hospital resource use is attributable to care for children with neurological impairments, although it's thought that this group may account for an increasing proportion of hospital resources. In this study, the researchers attempted to answer this question, specifically for the US, by evaluating national trends in hospital admissions for children with neurological impairments.
What Did the Researchers Do and Find?
The researchers used a multi-state database of US hospital admissions for children aged 0–18 years, known as the KID—the Healthcare Cost and Utilization Project's Kids' Inpatient Database—to identify the number of hospital admissions, total number of days spent in the hospital, and total health care costs for children with neurological impairments from 1997 to 2006. The researchers identified appropriate admissions by using diagnostic codes from the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), which were reviewed and approved by two pediatric neurologists.
The researchers found that from 1997 to 2006, there were 25,747,016 hospital admissions for children aged 0–18 years, and of these, 1,338,590 (5.2%) were associated with children who had a definite diagnosis of neurological impairment. The most prevalent diagnoses among all hospitalized children with neurological impairments were epilepsy (52.2%) and cerebral palsy (15.9%). Furthermore, across the study period, the proportion of children aged 13–18 years admitted to hospitals with neurological impairments increased from 7.3% to 9.9%. The researchers also found that children with neurological impairments accounted for an increasing proportion of days spent in a hospital (12.9% in 1997 to 13.9% in 2006). In addition, there was a substantial increase in admissions for infants with neurological impairments compared to infants without neurological impairments. The researchers also found that throughout the study period, there was a general pattern for children with neurological impairments to be admitted to pediatric hospitals, rather than general hospitals. Within children's hospitals, children with neurological impairments accounted for a substantial proportion of resources over the study period, including nearly one-third of all hospital charges.
What Do These Findings Mean?
These findings show that in the US, children with neurological impairments account for a substantial proportion of inpatient resources utilized, particularly within children's hospitals, necessitating the need for adequate clinical care and a coordination of efforts to ensure that the needs of children with neurological impairments are met. System-based efforts such as partnerships between hospitals and families of children with neurological impairments and the rigorous evaluation of care treatment strategies have the potential to promote quality care for children with neurological impairments. However, such efforts will work only if the current health care system is adequately staffed with appropriately educated professionals.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/pmed.1001158.
More information is available about the KID database used in this study
NHS Choices has further information about epilepsy, one of the most common types of neurological impairment examined in this study
Further information is available from PubMed Health about cerebral palsy, another neurological condition acquired during development that was studied in this dataset
doi:10.1371/journal.pmed.1001158
PMCID: PMC3260313  PMID: 22272190
9.  Do medically unexplained symptoms matter? A prospective cohort study of 300 new referrals to neurology outpatient clinics 
OBJECTIVES—To determine (a) the proportion of patients referred to general neurology outpatient clinics whose symptoms are medically unexplained; (b) why they were referred; (c) health status and emotional disorder in this group compared with patients whose symptoms are explained by "organic" neurological disease.
METHODS—The prospective cohort study with case note follow up at 6 months was carried out in the regional neurology service in Lothian, Scotland with 300 newly referred outpatients. Neurologists rated the degree to which patients' symptoms were explained by organic disease (organicity), GPs' reasons for referral, health status (SF-36), anxiety, and depressive disorders (PRIME-MD),
RESULTS—Of 300 new patients 11% (95% confidence interval (95% CI) 7%-14%) had symptoms that were rated as "not at all explained" by organic disease, 19% (15% to 23%) "somewhat explained", 27% (22% to 32%) "largely explained", and 43% (37% to 49%) "completely explained" by organic disease. Reason for referral was not associated with "organicity". Comparison of these groups showed that although physical function was similar, the median number of physical symptoms and pain were greater in patients with lower organicity ratings (p<0.0005, p<0.0005). Depressive and anxiety disorders were more common in patients with symptoms of lower organicity (70% of patients in the not at all group had an anxiety or depressive disorder compared with 32% in the completely explained group (p<0.0005).
CONCLUSION—One third of new referrals to general neurology clinics have symptoms that are poorly explained by identifiable organic disease. These patients were disabled and distressed. They deserve more attention.


doi:10.1136/jnnp.68.2.207
PMCID: PMC1736779  PMID: 10644789
10.  Are aluminium potroom workers at increased risk of neurological disorders? 
OBJECTIVE: To determine whether long term potroom workers in an aluminium smelter are at increased risk of neurological disorders. METHODS: Cross sectional study of 63 current and former aluminium potroom workers first employed before 1970 and with at least 10 years of service. A group of 37 cast house and carbon plant workers with similar durations of employment and starting dates in the same smelter were used as controls. The prevalence of neurological symptoms was ascertained by questionnaire. Objective tests of tremor in both upper and lower limbs, postural stability, reaction time, and vocabulary were conducted. All subjects were examined by a neurologist. RESULTS: No significant differences in age, race, or education were found between the two groups. Although the potroom group had higher prevalences for all but one of the neurological symptoms, only three odds ratios (ORs) were significantly increased; for incoordination (OR 10.6), difficulty buttoning (OR 6.2), and depression (OR 6.2). Tests of arm or hand and leg tremor in both the visible and non-visible frequencies did not show any significant differences between the two groups. Testing of postural stability showed no definitive pattern of neurologically meaningful differences between the groups. There were no significant differences between the two groups in reaction time, vocabulary score, or clinical neurological assessment. CONCLUSIONS: The objective measures of neurological function provided little support for the finding of increased neurological symptom prevalences in the potroom workers, although increased symptoms may be an indicator of early, subtle neurological changes. The results provide no firm basis for concluding that neurological effects among long term potroom workers are related to the working environment, in particular aluminium exposure, in potrooms. These findings should be treated with caution due to the low participation of former workers and the possibility of information bias in the potroom group.
PMCID: PMC1128695  PMID: 9166127
11.  Medical healthcare use in Parkinson's disease: survey in a cohort of ambulatory patients in Italy 
Background
Parkinson's disease (PD) is a chronic neurodegenerative disease which at present has no cure, and it usually results in severe disability. The burden of PD increases as the illness progresses, resulting in the extensive utilisation of both health and community services. Knowledge of healthcare use patterns and of their determinants may greatly contribute to improve patient care, however few studies have examined this issue in PD. The present study was devised to describe the type of and reasons for medical healthcare resource use in persons with PD attending a Centre for PD and Movement Disorders, and to examine drug prescriptions issued on such occasions.
Methods
The study was a retrospective, cross-sectional survey in a cohort of ambulatory patients with PD, conducted by means of standard interviews.
Results
In the year before the study, 92 (70.8%) of 130 patients used medical healthcare resources: 1/5 of the patients was admitted to hospital, 1/5 to emergency room, 2/5 were visited by a non-neurology specialist, and 1/4 by the GP. Reasons were: nearly 20% programmed hospital admissions and visits, and more than 25% injuries and musculo-skeletal diseases. Other conditions typically occurring in PD (e.g. dementia, diabetes and cardio- and cerebro-vascular disease) were less frequently involved. On such occasions, drugs for PD were occasionally changed, however drug prescriptions for other indications were issued to more than 66% of the patients.
Conclusion
Several physicians other than the neurologist may take care of PD patients on different occasions, thus emphasising the need for communication between the reference neurologist and other physicians who from time to time may visit the patient.
doi:10.1186/1472-6963-5-26
PMCID: PMC1079835  PMID: 15790401
12.  Survey of Medication Usage Patterns Among Essential Tremor Patients: Movement Disorder Specialists vs. General Neurologists 
Parkinsonism & related disorders  2010;16(9):604-607.
Background
Although small treatment trials have examined the efficacy of front-line medications in tremor reduction in essential tremor (ET), an overall survey of pharmacological management has not been undertaken in a large sample of ET cases.
Objectives
To conduct a survey of medication usage among several hundred ET patients.
Methods
A computerized database at the Neurological Institute of New York was used to identify 223 ET patients cared for by movement disorder neurologists and 37 cared for by general neurologists. Each had been seen one or more times within past five years. Lifetime treatment data were abstracted from clinical records.
Results
One-hundred-sixty-three (73.1%) of 223 patients cared for by movement disorder neurologists had taken medication for ET during their lifetime; 53/163 (32.5%) had taken ≥4 medications; 31/163 (19.0%) had taken ≥5 medications; and 3 (1.8%), ≥10 medications. Nearly three-quarters (158/223 [70.9%]) had taken primidone or propranolol, yet 89/158 (56.3%) had discontinued both. Among 11 patients who had undergone ET surgery, the mean number of ET medications tried was 6.0±2.8 (range = 3–12). Medication usage by general neurologists was less than by movement disorder specialists (p<0.001). One-third of general neurologists’ patients (14/37 [37.8%]) had taken primidone or propranolol at some point and 6/14 (42.9%) had discontinued both.
Conclusions
In this large survey, a substantial proportion of ET patients failed treatment with both front-line medications. Among patients seeing movement disorder specialists, the number of medications they had had to try was sizable. These data demonstrate the limitations of current pharmacological options for ET.
doi:10.1016/j.parkreldis.2010.07.011
PMCID: PMC2963696  PMID: 20691629
Essential tremor; clinical; epidemiology; treatment; medication
13.  Treatment selection and experience in multiple sclerosis: survey of neurologists 
Background
Multiple sclerosis (MS) is a complex disease with many therapeutic options. Little is known about how neurologists select particular disease-modifying therapies (DMTs) for their patients.
Objective
To understand how neurologists make decisions regarding the prescription of DMTs for patients with MS, and to explore neurologists’ experiences with individual DMTs.
Methods
From December 2012 to January 2013, members of a nationwide physician market research panel were sent an online study invitation with a link to a survey website. Eligible neurologists were included if they currently practice medicine in the United States, and if they treat ≥20 patients with MS.
Results
A total of 102 neurologists (n=63 general neurologists; n=39 MS specialists; 81.4% male) completed the survey. The mean (standard deviation) number of years in practice since completing medical training was 16.4 (8.6) years. Overall, the most commonly prescribed DMTs were subcutaneous interferon (IFN) β-1a and glatiramer acetate; approximately 5.5% of patients were untreated. The most important attributes of DMT medication selection were (in order of importance) efficacy, safety, tolerability, patient preference, and convenience. The DMT with the highest neurologist-reported percentage of patients who were “Very/Extremely Satisfied” with their therapy was fingolimod (31.0%), followed by glatiramer acetate (13.9%; P=0.017). Compared with fingolimod (94.0%), significantly fewer (P<0.05) neurologists reported that “All/Most” of their patients were adherent to treatment with glatiramer acetate (78.0%), subcutaneous IFN β-1a (84.0%), and IFN β-1b (75.0%); no significant differences were observed with intramuscular IFN β-1a (92.9%; P=0.75). Patients’ calls to neurologists’ offices were most commonly related to side effects for all self-injectable DMTs, whereas calls about fingolimod primarily involved insurance coverage issues.
Conclusion
Our survey results showed that very few patients with MS did not received any DMT. Among the DMTs available at the time of the survey, neurologists reported that patients were most satisfied with, and adherent to, fingolimod, but these patients also faced more problems with insurance coverage when compared with those taking self-injectable DMTs.
doi:10.2147/PPA.S53140
PMCID: PMC3979792  PMID: 24729689
multiple sclerosis; disease-modifying therapy; physician survey; treatment selection; treatment adherence; treatment satisfaction
14.  How do patients referred to neurologists for headache differ from those managed in primary care? 
Background
Headache is the neurological symptom most frequently presented to GPs and referred to neurologists, but little is known about how referred patients differ from patients managed by GPs.
Aim
To describe and compare headache patients managed in primary care with those referred to neurologists.
Design of study
Prospective study.
Setting
Eighteen general practices in south-east England.
Method
This study examined 488 eligible patients consulting GPs with primary headache over 7 weeks and 81 patients referred to neurologists over 1 year. Headache disability was measured by the Migraine Disability Assessment Score, headache impact by the Headache Impact Test, emotional distress by the Hospital Anxiety and Depression Scale and illness perception was assessed using the Illness Perception Questionnaire.
Results
Participants were 303 patients who agreed to participate. Both groups reported severe disability and very severe impact on functioning. Referred patients consulted more frequently than those not referred in the 3 months before referral (P = 0.003). There was no significant difference between GP-managed and referred groups in mean headache disability, impact, anxiety, depression, or satisfaction with care. The referred group were more likely to link an increased number of symptoms to their headaches (P = 0.01), to have stronger emotional representations of their headaches (P = 0.006), to worry more (P = 0.001), and were made anxious by their headache symptoms (P = 0.044).
Conclusion
Patients who consult for headache experience severe disability and impact, and up to a third report anxiety and/or depression. Referral is not related to clinical severity of headaches, but is associated with higher consultation frequency and patients' anxiety and concern about their headache symptoms.
PMCID: PMC2047014  PMID: 17504590
headache; migraine disorders; neurology; primary health care; referral and consultation
15.  The outcome of neurology outpatients with medically unexplained symptoms: a prospective cohort study 
Background: In a previous cross sectional study of 300 consecutive new attenders at neurology outpatient clinics, 90 were detected with symptoms that were rated as "not at all" or only "somewhat" explained by organic disease.
Objective: To report a follow up study of this cohort.
Methods: Patients were reinterviewed by telephone eight months after their initial assessment. They were asked to rate their overall improvement on a clinical global improvement scale, and their health status on the medical outcome short form 36 item scale (SF-36). The PRIME MD interview was administered to determine psychiatric diagnoses. Neurological and primary care records were reviewed for any changes in diagnostic opinion during the follow up period.
Results: Of the 90 eligible patients, 66 (73%) participated in follow up. Among these, five (8%) rated themselves as "much worse," four (6%) as "somewhat worse," 27 (40%) as "just the same," 15 (23%) as "somewhat better," and 15 (23%) as "much better." There were no cases in which an organic cause for the presenting complaint was uncovered during the follow up period. Poorer physical function at baseline was the only predictor of poorer outcome at follow up.
Conclusions: Over half the patients who presented to neurologists with symptoms that were rated as largely or completely medically unexplained had not improved eight months later. In no case was a disease explanation for the original presenting symptoms subsequently identified.
doi:10.1136/jnnp.74.7.897
PMCID: PMC1738573  PMID: 12810775
16.  Health inequalities as a foundation for embodying knowledge within public health teaching: a qualitative study 
Introduction
Recent UK health policies identified nurses as key contributors to the social justice agenda of reducing health inequalities, on the assumption that all nurses understand and wish to contribute to public health. Following this policy shift, public health content within pre-registration nursing curricula increased. However, public health nurse educators (PHNEs) had various backgrounds, and some had limited formal public health training, or involvement in or understanding of policy required to contribute effectively to it. Their knowledge of this subject, their understanding and interpretation of how it could be taught, was not fully understood.
Methodology
This research aimed to understand how public health nurse educators’ professional knowledge could be conceptualised and to develop a substantive theory of their knowledge of teaching public health, using a qualitative data analysis approach. Qualitative in-depth semi-structured interviews (n=26) were conducted with eleven university-based PHNEs.
Results
Integrating public health into all aspects of life was seen as central to the knowing and teaching of public health; this was conceptualised as ‘embodying knowledge’. Participants identified the meaning of embodying knowledge for teaching public health as: (a) possessing a wider vision of health; (b) reflecting and learning from experience; and (c) engaging in appropriate pedagogical practices.
Conclusion
The concept of public health can mean different things to different people. The variations of meaning ascribed to public health reflect the various backgrounds from which the public health workforce is drawn. The analysis indicates that PHNEs are embodying knowledge for teaching through critical pedagogy, which involves them engaging in transformative, interpretive and integrative processes to refashion public health concepts; this requires PHNEs who possess a vision of what to teach, know how to teach, and are able to learn from experience. Their vision of public health is influenced by social justice principles in that health inequalities, socioeconomic determinants of health, epidemiology, and policy and politics are seen as essential areas of the public health curriculum. They believe in forms of teaching that achieve social transformation at individual, behavioural and societal levels, while also enabling learners to recognise their capacity to effect change.
doi:10.1186/1475-9276-12-46
PMCID: PMC3698137  PMID: 23809694
Social Justice; Inequalities in Health; Public Health; Embodying Knowledge
17.  Mild cognitive impairment in clinical care 
Neurology  2010;75(5):425-431.
Objective:
To assess how neurologists view mild cognitive impairment (MCI) as a clinical diagnosis and how they treat patients with mild cognitive symptoms.
Methods:
Members of the American Academy of Neurology with an aging, dementia, or behavioral neurology practice focus were surveyed by self-administered questionnaire.
Results:
Survey respondents were 420 providers (response rate 48%), and 88% reported at least monthly encounters with patients experiencing mild cognitive symptoms. Most respondents recognize MCI as a clinical diagnosis (90%) and use its diagnostic code for billing purposes (70%). When seeing these patients, most respondents routinely provide counseling on physical (78%) and mental exercise (75%) and communicate about dementia risk (63%); fewer provide information on support services (27%) or a written summary of findings (15%). Most (70%) prescribe cholinesterase inhibitors at least sometimes for this population, with memantine (39%) and other agents (e.g., vitamin E) prescribed less frequently. Respondents endorsed several benefits of a diagnosis of MCI: 1) involving the patient in planning for the future (87%); 2) motivating risk reduction activities (85%); 3) helping with financial planning (72%); and 4) prescribing medications (65%). Some respondents noted drawbacks, including 1) too difficult to diagnose (23%); 2) better described as early Alzheimer disease (21%); and 3) diagnosis can cause unnecessary worry (20%).
Conclusions:
Patients with mild cognitive symptoms are commonly seen by neurologists, who view MCI as a useful diagnostic category. Information and treatments provided to patients with MCI vary significantly, suggesting a need for practice guidelines and further research on clinical decision-making with this population.
GLOSSARY
= age-associated memory impairment;
= American Academy of Neurology;
= Alzheimer disease;
= cognitive impairment, no dementia;
= Diagnostic and Statistical Manual of Mental Disorders, 5th edition;
= mild cognitive impairment;
= not otherwise specified.
doi:10.1212/WNL.0b013e3181eb5872
PMCID: PMC2918467  PMID: 20679636
18.  Psychiatric illness in inpatients with neurological disorders: patients' views on discussion of emotional problems with neurologists. 
The prevalence of psychiatric morbidity in inpatients with neurological disorders and the extent to which it is detected by neurologists were measured by using a two stage model of psychiatric assessment and from information recorded in the patients' medical notes. The prevalence of psychiatric morbidity was estimated as 39%, of which 72% was unrecognised by the neurologists. Only a minority of patients with an uncertain physical diagnosis had a psychiatric illness, showing the error in assuming that a patient's physical symptoms arise from a psychological disturbance if an organic aetiology cannot be determined. When the patients were interviewed on their discharge from hospital they were divided on whether they had wished to discuss their mood with neurologists while they were in hospital. The reasons that they gave suggested that interactions between patients and doctors and the lack of ward facilities for private consultations with doctors are important determinants of hidden psychiatric morbidity in medical inpatients.
PMCID: PMC1443098  PMID: 6434026
19.  Inter-Rater Agreement in the Clinical Diagnosis of Essential Tremor: Data from the NEDICES-2 Pilot Study 
Tremor and Other Hyperkinetic Movements  2014;4:tre-04-187-4774-3.
Background
Our aim was to assess the diagnostic agreement among the neurologists in the Neurological Disorders in Central Spain 2 (NEDICES-2) study; these neurologists were assigning diagnoses of essential tremor (ET) vs. no ET.
Methods
Clinical histories and standardized video-taped neurological examinations of 26 individuals (11 ET, seven Parkinson’s disease, three diagnostically unclear, four normal, one with a tremor disorder other than ET) were provided to seven consultant neurologists, six neurology residents, and five neurology research fellows (18 neurologists total). For each of the 26 individuals, neurologists were asked to assign a diagnosis of “ET” or “no ET” using diagnostic criteria proposed by the Movement Disorders Society (MDS). Inter-rater agreement was assessed both with percent concordance and non-weighted κ statistics.
Results
Overall κ was 0.61 (substantial agreement), with no differences between consultant neurologists (κ = 0.60), neurology residents (κ = 0.61), and neurology research fellows (κ = 0.66) in subgroup analyses. Subanalyses of agreement only among those 15 subjects with a previous diagnosis of ET (11 patients) and those with a previous diagnosis of being normal (four individuals) showed an overall κ of 0.51 (moderate agreement).
Discussion
In a population-based epidemiological study, substantial agreement was demonstrated for the diagnosis of ET among neurologists of different levels of expertise. However, agreement was lower than that previously reported using the Washington Heights–Inwood Genetic Study of Essential Tremor criteria, and a head-to-head comparison is needed to assess which is the tool of choice in epidemiological research in ET.
doi:10.7916/D8JD4TQ0
PMCID: PMC3918509  PMID: 24587969
Tremor, essential tremor; clinical diagnosis; inter-rater agreement; reliability
20.  Pattern of neurological disease seen among patients admitted in tertiary care hospital 
BMC Research Notes  2014;7:202.
Background
Neurologic disorders are not uncommon at in patient departments of different hospitals. We have conducted the study to see the pattern and burden of neurologic disorders at different inpatient departments of a tertiary care centre.
Methodology
This retrospective observational study was carried out from the records and referral notes of neurology department of Dhaka Medical College Hospital (DMCH) from July 2011 to June 2012. A total 335 patients were evaluated by consultant neurologists during this period.
Result
Majority of the patients (59.7%) presented after the age of forty years. The mean age at presentation was 45.11 ± 17.3 years with a male predominance (63.3%). Stroke was the most common condition (47.5%) observed at referral, followed by seizure (9.3%), disease of spinal cord (7.8%) and encephalopathy (6.3%). Even after consultation, 30 patients remained undiagnosed and 6 were diagnosed as functional disorder. Department of Medicine (231, 69%) and Cardiology (61, 18.2%) made most of the calls. More than half (56%) of the stroke patients were referred from medicine and one third (35.2%) from cardiology. Seizure (67.7%), problem in spinal cord (92.3%), coma (50%), encephalopathy (57.1%), motor neuron disease (MND) (72.7%) were common reasons for referral from department of Medicine. Whereas patients with cord disease (7.3%), CNS tumor (40%), seizure disorder (6.5%) and stroke (3.8%) were referred from surgery. Department of Obstetrics and Gynecology sought help for stroke (2.5%), seizure (12.9%), MND (27.3%), coma (16.7%) and encephalopathy (9.5%).
Hypertension, diabetes, ischemic heart disease, dyslipidaemia and respiratory problem were significantly associated co-morbid conditions in stroke patients (at 95% CI, p value is <0.001, <0.01, <0.001, <0.05, <0.05 respectively). Hematological disorders were common association among patients with cord problem (<0.05).
Conclusion
Wide ranges of neurological problems are often managed by physicians and surgeons, especially those from medicine and cardiology. Where ever available consultation from neurologists can help in diagnosing and managing these cases.
doi:10.1186/1756-0500-7-202
PMCID: PMC3977680  PMID: 24684800
Neurologic disease
21.  Unified Parkinson’s Disease Rating Scale-Motor Exam: Inter-rater reliability of advanced practice nurse and neurologist assessments 
Journal of advanced nursing  2010;66(6):1382-1387.
Aim
This paper is a report of a study to establish the inter-rater reliability of advanced practice nurse and neurologist neurological assessments which included ratings with the Unified Parkinson’s Disease Rating Scale-Motor Exam.
Background
Around the world, advanced practice nurses are performing tasks once completed by only physicians. To promote consumer and provider confidence, it is important to establish that nurse and physician ratings using assessment tools are similar. In addition in research settings, when different raters are used, establishment of inter-rater reliability for study assessments is needed.
Method
Advanced practice nurses and neurologists independently recorded findings on neurological examinations of 46 participants in a study conducted between August 2007 and January 2008. An intraclass correlation coefficient was calculated to estimate overall agreement between the nurse and neurologist ratings. Agreement for individual items measured on a dichotomous scale was assessed by calculating Cohen’s kappa.
Results
There was substantial agreement between advanced practice nurses and neurologists on the mean Unified Parkinson’s Disease Rating Scale-Motor Exam ratings (intraclass correlation coefficient = 0.65) and the U.S. National Alzheimer’s Coordinating Center Uniform Data Set neurological examination ratings of unremarkable findings (kappa = 0.74) and of gait disorder (kappa = 0.73). Moderate agreement (kappa = 0.53) was reached for the rating of whether all Unified Parkinson’s Disease Rating Scale-Motor Exam items were normal.
Conclusion
These findings are consistent with studies of the inter-rater agreement of the Unified Parkinson’s Disease Rating Scale-Motor Exam and support the conduct of neurological assessments by advanced practice nurses.
doi:10.1111/j.1365-2648.2010.05313.x
PMCID: PMC2903978  PMID: 20546368
Unified Parkinson’s Disease Rating Scale; advanced practice nurse; neurologist; inter-rater reliability; neurological examination
22.  Current clinical practice for Parkinson’s disease among Chinese physicians, general neurologists and movement disorders specialists: a national survey 
BMC Neurology  2012;12:155.
Background
To explore current status and choices regarding diagnosis and treatment of Parkinson’s disease (PD) among physicians, general neurologists and movement disorders specialists in China via a national survey.
Methods
The cross-sectional questionnaire-based survey was conducted from November, 2010 to July, 2011. Six hundreds and twelve doctors from different cities in China were recruited for this study.
Results
68.6% (n=420) and 23.9% (n=146) of doctors have read the national and international guidelines, respectively. There was a larger proportion of movement disorders specialists reading the guidelines, in contrast to physicians and general neurologists (P<0.001). Up to 76.4% (n=465) and 81.8% (n=498) of doctors would choose standard oral levodopa test and conventional MRI(with T1 and T2), respectively; Whereas susceptibility weighed imaging(SWI)(16.1%; n=98), transcranial sonography (TCS) (1.8%; n=11) and functional neuroimaging test, such as single photon emission computed tomography(SPECT) (10.2%; n=62) and positron emission tomography(PET)(13.3%; n=81) were less used for suspected patients with PD in clinical practice. Doctors at different levels or from different hospitals and cities would choose different medication for motor complications and non-motor symptoms of patients with PD, in addition to initial drug selection for newly diagnosed PD. Doctors who had read the guidelines had significantly better knowledge of medication selections for PD under specific circumstances.
Conclusions
Compared with commonly employed standard oral levodopa test and conventional MRI, SWI complements MRI, TCS and functional neuroimaging were less performed for diagnosis of PD in clinical practice in China. The choices of diagnostic methods and therapeutic strategy of PD vary among physicians, general neurologists and movement disorders specialists. Guideline awareness is markedly beneficial to reasonable PD medications strategy in China.
doi:10.1186/1471-2377-12-155
PMCID: PMC3538053  PMID: 23216699
Parkinson’s disease; National survey; Clinical practice guideline; Medication
23.  The role of emergency neurology in Italy: outcome of a consensus meeting for a intersociety position 
Neurological Sciences  2011;33(2):297-304.
A possible definition of clinical, educational and organizing aspects of emergency neurology in Italy is reported in this position paper of Emergency Neurology Intersociety Group, created in 2008 among the two neurological Societies in Italy: Società Italiana di Neurologia and Società di Neuroscienze Ospedaliere. The aim of this Group has been the evaluation of the role of neurologist in the emergency setting of Italian hospitals, as well as of the description of different scenarios in which a ward dedicated to a semi-intensive care of neurological emergencies could have a role in the actual organization of academic or general hospitals in our Country. The actual great relevance of neurologist activity in the inpatients treatment, in fact, is actually misleaded as it is the considerable significance of neurological expertise, techniques and support in hospital care pathways also involving neurological manifestations throughout the course of other diseases. Finally, the possible contents of educational programs orienting neurological specialty towards a better comprehension and management of emergency neurological problems either in terms of specific formation or of techniques to be learned by emergency neurologist, are reported as a results of the Consensus Workshop hold in Castiglioncello (LI) in September 12th, 2009.
doi:10.1007/s10072-011-0841-8
PMCID: PMC3313019  PMID: 22057314
Emergency neurology; Hospital setting; Neurological specialty; Organisational models
24.  The burden of headache disorders in Pakistan: methodology of a population-based nationwide study, and questionnaire validation 
Background
Large geographical gaps in our knowledge of the prevalence and burden of headache disorders include Pakistan, a country with major problems of poverty, illiteracy and security. We report implementation in this country of standard methods developed by Lifting The Burden (LTB) for population-based burden-of-headache studies.
Methods
We surveyed six locations from the four provinces: Lahore and Multan (Punjab), Karachi and Sukkur (Sindh), Abbottabad (Khyber Pakhtunkhwa) and Gwadar (Baluchistan). We randomly selected rural and urban households in each, which were visited by trained non-medical interviewers from the same locations. One randomly selected adult member (18–65 years) of each household was interviewed using LTB’s structured questionnaire translated into Urdu, the national language. Validation was performed among patients and accompanying attendants in three (urban and rural) medical facilities. After responding to the questionnaire, these participants were re-interviewed and diagnosed by a neurologist (gold standard).
Results
The survey was completed by 4,223 respondents (1,957 [46.3%] male, 2,266 [53.7%] female, 1,443 [34.2%] urban, 2,780 [65.8%] rural, mean age 34.4 ± 11.0 years). The participation rate was 89.5%. There were 180 participants (46.1% male, 53.9% female, 41.7% urban, 58.3% rural, mean age 39.4 ± 14.2 years) in the validation sample, of whom 147 (81.7%) reported headache in the last year. The questionnaire was 100% sensitive in screening for headache and for headache on ≥15 days/month, and showed good agreement with the gold-standard diagnoses (kappa = 0.77). It was relatively insensitive for TTH. The questionnaire’s default diagnosis of probable MOH when medication overuse accompanied headache on ≥15 days/month was not supported by evidence of causation in most cases seen by the neurologist. In public-health terms, precise diagnosis in these cases matters less than reliably detecting the coexistence of these disorders.
Conclusion
In conclusion, the methods developed by LTB were applied successfully in Pakistan, despite problems unique to this country.
doi:10.1186/1129-2377-14-73
PMCID: PMC3765424  PMID: 23967900
Migraine; Tension-type headache; Medication-overuse headache; Burden of disease; Epidemiology; Population-based survey; Pakistan; Global Campaign against headache
25.  Neurological diseases and pain 
Brain  2011;135(2):320-344.
Chronic pain is a frequent component of many neurological disorders, affecting 20–40% of patients for many primary neurological diseases. These diseases result from a wide range of pathophysiologies including traumatic injury to the central nervous system, neurodegeneration and neuroinflammation, and exploring the aetiology of pain in these disorders is an opportunity to achieve new insight into pain processing. Whether pain originates in the central or peripheral nervous system, it frequently becomes centralized through maladaptive responses within the central nervous system that can profoundly alter brain systems and thereby behaviour (e.g. depression). Chronic pain should thus be considered a brain disease in which alterations in neural networks affect multiple aspects of brain function, structure and chemistry. The study and treatment of this disease is greatly complicated by the lack of objective measures for either the symptoms or the underlying mechanisms of chronic pain. In pain associated with neurological disease, it is sometimes difficult to obtain even a subjective evaluation of pain, as is the case for patients in a vegetative state or end-stage Alzheimer's disease. It is critical that neurologists become more involved in chronic pain treatment and research (already significant in the fields of migraine and peripheral neuropathies). To achieve this goal, greater efforts are needed to enhance training for neurologists in pain treatment and promote greater interest in the field. This review describes examples of pain in different neurological diseases including primary neurological pain conditions, discusses the therapeutic potential of brain-targeted therapies and highlights the need for objective measures of pain.
doi:10.1093/brain/awr271
PMCID: PMC3281476  PMID: 22067541
brain imaging; Parkinson's disease; complex regional pain syndrome; migraine; brain trauma

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