Repetitive transcranial magnetic stimulation plus standardized suggestion of benefit for functional movement disorders: an open label case series.

BACKGROUND: We studied suggestion of benefit combined with motor cortex and premotor cortex repetitive transcranial magnetic stimulation (rTMS) in chronic (>2 years) FMDs. METHODS: Patients were identified from our patient records who had clinically definite FMDs and had undergone neuropsychiatric evaluation. Those with chronic FMDs were offered open-label rTMS over the dominant motor cortex. If they failed to improve they received dominant premotor cortex rTMS. The primary outcome was change from baseline to post-rTMS in quality of life measured by the World Health Organization Quality of Life Brief (WHOQOL-BREF) scale. Secondary outcomes were subject and investigator global impression of change (GIC), blinded Rush psychogenic movements rating scale, Barbers suggestibility scale, baseline expectation of benefit scale, and adverse effects. RESULTS: Six subjects were enrolled. For the primary outcome, there was significant improvement in the physical domain scores but significant reduction in psychological domain scores after premotor cortex rTMS compared to baseline and after motor cortex rTMS. There was no significant change between baseline and motor cortex rTMS or in any other domain after premotor cortex rTMS. Secondary outcome measures showed no meaningful change. Transient headache and worsening of FMD symptoms were the most common adverse effects observed. CONCLUSION: rTMS combined with strong suggestion of benefit provided dissonant results after premotor cortex rTMS with improvement in physical quality of life but reduction in psychological quality of life. These results serve to underscore the complex nature of FMDs where the overt physical manifestation is but one part of a comprehensive neuropsychological syndrome.

Subjectively perceived personality and mood changes associated with subthalamic stimulation in patients with Parkinson's disease.

BACKGROUND: Clinical and ethical implications of personality and mood changes in Parkinson's disease (PD) patients treated with subthalamic deep brain stimulation (STN-DBS) are under debate. Although subjectively perceived personality changes are often mentioned by patients and caregivers, few empirical studies concerning these changes exist. Therefore, we analysed subjectively perceived personality and mood changes in STN-DBS PD patients. METHOD: In this prospective study of the ELSA-DBS group, 27 PD patients were assessed preoperatively and 1 year after STN-DBS surgery. Two categories, personality and mood changes, were analysed with semi-structured interviews. Patients were grouped into personality change yes/no, as well as positive/negative mood change groups. Caregivers were additionally interviewed about patients' personality changes. Characteristics of each group were assessed with standard neurological and psychiatric measurements. Predictors for changes were analysed. RESULTS: Personality changes were perceived by six of 27 (22%) patients and by 10 of 23 caregivers (44%). The preoperative hypomania trait was a significant predictor for personality change perceived by patients. Of 21 patients, 12 (57%) perceived mood as positively changed. Higher apathy and anxiety ratings were found in the negative change group. CONCLUSIONS: Our results show that a high proportion of PD patients and caregivers perceived personality changes under STN-DBS, emphasizing the relevance of this topic. Mood changed in positive and negative directions. Standard measurement scales failed to adequately reflect personality or mood changes subjectively perceived by patients. A more individualized preoperative screening and preparation for patients and caregivers, as well as postoperative support, could therefore be useful.

Drug-induced deactivation of inhibitory networks predicts pathological gambling in PD.

OBJECTIVE: Some patients with Parkinson disease (PD) develop pathological gambling when treated with dopamine agonists (DAs). However, little is known about DA-induced changes in neuronal networks that may underpin this drug-induced change in behavior in vulnerable individuals. In this case-control study, we aimed to investigate DA-induced changes in brain activity that may differentiate patients with PD with DA-induced pathological gambling (gamblers) from patients with PD without such a history (controls). METHODS: Following overnight withdrawal of antiparkinsonian medication, patients were studied with H2(15)O PET before and after administration of DA (3 mg apomorphine) to measure changes in regional cerebral blood flow as an index of regional brain activity during a card selection game with probabilistic feedback. RESULTS: We observed that the direction of DA-related activity change in brain areas that are implicated in impulse control and response inhibition (lateral orbitofrontal cortex, rostral cingulate zone, amygdala, external pallidum) distinguished gamblers from controls. DA significantly increased activity in these areas in controls, while gamblers showed a significant DA-induced reduction of activity. CONCLUSIONS: We propose that in vulnerable patients with PD, DAs produce an abnormal neuronal pattern that resembles those found in nonparkinsonian pathological gambling and drug addiction. DA-induced disruption of inhibitory key functions--outcome monitoring (rostral cingulate zone), acquisition and retention of negative action-outcome associations (amygdala and lateral orbitofrontal cortex)--together with restricted access of those areas to executive control (external pallidum)--may well explain loss of impulse control and response inhibition in vulnerable patients with PD, thereby fostering the development of pathological gambling.

Increased striatal dopamine release in Parkinsonian patients with pathological gambling: a [11C] raclopride PET study.

Pathological gambling is an impulse control disorder reported in association with dopamine agonists used to treat Parkinson's disease. Although impulse control disorders are conceptualized as lying within the spectrum of addictions, little neurobiological evidence exists to support this belief. Functional imaging studies have consistently demonstrated abnormalities of dopaminergic function in patients with drug addictions, but to date no study has specifically evaluated dopaminergic function in Parkinson's disease patients with impulse control disorders. We describe results of a [(11)C] raclopride positron emission tomography (PET) study comparing dopaminergic function during gambling in Parkinson's disease patients, with and without pathological gambling, following dopamine agonists. Patients with pathological gambling demonstrated greater decreases in binding potential in the ventral striatum during gambling (13.9%) than control patients (8.1%), likely reflecting greater dopaminergic release. Ventral striatal bindings at baseline during control task were also lower in patients with pathological gambling. Although prior imaging studies suggest that abnormality in dopaminergic binding and dopamine release may be markers of vulnerability to addiction, this study presents the first evidence of these phenomena in pathological gambling. The emergence of pathological gambling in a number of Parkinson's disease patients may provide a model into the pathophysiology of this disorder.

Pain characteristics of adults 65 years of age and older referred to a tertiary care pain clinic.

BACKGROUND: Reports indicate that characteristics of older adults with chronic pain may be different than those of younger persons. OBJECTIVE: To study the pain characteristics of older patients presenting to a tertiary pain clinic for the first time. METHODS: Age, sex and relative contributions of biomedical versus psychosocial variables contributing to chronic pain were investigated in patients 65 years of age and older, in comparison with younger patients, from a sample of 1242 consecutive new patients attending a tertiary care pain clinic. The presence of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision somatoform pain disorders were defined, using an explicated method of ascertaining the biomedical and psychological variables underlying the pain complaints. RESULTS: The older patients (14.7% of the total sample) had relatively more physical problems (concordant with their complaints) but fewer psychological factors contributing to disability than the younger pain patients. Musculoskeletal and neuropathic disorders affected 40.7% and 35.2% of the older patients, respectively, while several patients had more than one painful disorder. Musculoskeletal problems were more prevalent in the women, and neuropathic problems were more prevalent in the men. CONCLUSIONS: The older pain patients are a distinct group. Factors affecting the delayed presentation of older pain patients to the pain clinic and limitations of the present study are discussed.

Pain characteristics and demographics of patients attending a university-affiliated pain clinic in Toronto, Ontario.

BACKGROUND: Pain clinics tend to see more complex chronic pain patients than primary care settings, but the types of patients seen may differ among practices. OBJECTIVE: The aim of the present observational study was to describe the pain and demographic characteristics of patients attending a university-affiliated tertiary care pain clinic in Toronto, Ontario. METHODS: Data were collected on 1242 consecutive new patients seen over a three-year period at the Comprehensive Pain Program in central Toronto. RESULTS: Musculoskeletal problems affecting large joints and the spine were the predominant cause of pain (more prevalent in women), followed by neuropathic disorders (more prevalent in men) in patients with recognizable physical pathology. The most affected age group was in the 35- to 49-year age range, with a mean pain duration of 7.8 years before the consultation. While 77% of the Comprehensive Pain Program patients had relevant and detectable physical pathology for pain complaints, three-quarters of the overall study population also had significant associated psychological or psychiatric comorbidity. Women, in general, attended the pain clinic in greater numbers and had less apparent physical pathology than men. Finally, less than one in five patients was employed at the time of referral. CONCLUSIONS: The relevance of the data in relation to other pain clinics is discussed, as well as waiting lists and other barriers faced by chronic pain patients, pain practitioners and pain facilities in Ontario and Canada.

Ethnocultural and sex characteristics of patients attending a tertiary care pain clinic in Toronto, Ontario.

BACKGROUND: Ethnocultural factors and sex may greatly affect pain perception and expression. Emerging literature is also documenting racial and ethnic differences in pain access and care. OBJECTIVE: To define the sex and ethnocultural characteristics of patients attending a tertiary care, university-affiliated pain clinic in Toronto, Ontario. METHODS: Data were collected on 1242 consecutive, new patients seen over a three-year period at the Comprehensive Pain Program (CPP) in downtown Toronto. Data were compared with the Canada 2001 Census. RESULTS: English-speaking, Canadian-born patients constituted 58.6% of the CPP population, similar to the 2001 Canadian Census data for the Greater Toronto Area. Certain visible minority groups (Indo-Pakistani and Chinese) were significantly under-represented, while European groups were over-represented. While women outnumbered men, they presented with lower levels of physical pathology in general, particularly in certain ethnic groups. Patients from Europe (representing primarily immigrants who arrived in Canada before 1960), were older, by 10 years to 15 years, than the average CPP population, and had a much higher incidence of physical or medical disorders. CONCLUSIONS: The implications of the study and the importance of sex and ethnicity in terms of presentation to Canadian pain clinics are discussed. Future well-designed studies are needed to shed light on the role of both patients' and physicians' ethnicity and sex in pain perception and expression, decision-making regarding pain treatments and acceptance of pain treatments.

Prevalence of repetitive and reward-seeking behaviors in Parkinson disease.

We surveyed 297 patients with Parkinson disease (PD) with systematic screens and rigorous definitional criteria. Pathologic hypersexuality lifetime prevalence was 2.4%. Compulsive shopping was 0.7%. Combined with our pathologic gambling data, the lifetime prevalence of these behaviors was 6.1% and increases to 13.7% in patients on dopamine agonists.

Prospective prevalence of pathologic gambling and medication association in Parkinson disease.

The authors prospectively screened 297 patients with Parkinson disease (PD), who attended a tertiary clinic, using a modified South Oaks Gambling Scale. Lifetime prevalence of pathologic gambling (PG) was 3.4% and on any dopamine agonist was 7.2%. PG was associated with earlier PD onset and with dopamine agonists but not with agonist subtype or doses. We found no association with a potent D3 receptor agonist.

Sympathetic denervation impairs epidermal healing in cutaneous wounds.

The involvement of peripheral nerves in dermal wound healing, particularly in the inflammatory response has not been extensively studied. Therefore, this study was performed to examine the role of peripheral nerves in the healing of rat skin linear incisions. We report that chemical sympathectomy with 6-hydroxydopamine significantly impaired wound healing as measured on days 7, 11, and 14 postsurgery (by day 14, 48% of the sympathectomized rats were healed in contrast with 84% of the controls; p = 0.0104). In contrast, neonatal capsaicin treatment, which predominantly destroys sensory afferents, had no effect on wound healing (p > 0.05 on all days). These results support the hypothesis that sympathetic efferents are important for wound healing. Unlike previous research, which showed that peripheral nerves influence ischemic skin flaps, we are the first to demonstrate a role for peripheral nerves in the healing of skin incisions. Because inflammation is an important step in cutaneous wound healing, we propose that a reduction of neurogenic inflammation caused by sympathectomy may explain the impaired wound healing that we observed in our study.