Potential therapeutic benefit of spinal cord stimulation in restless legs syndrome: scoping review and mechanistic considerations.

BACKGROUND: Restless legs syndrome (RLS) is a prevalent sensorimotor disorder that can dramatically impair sleep quality, daytime function, and quality of life. Although many patients benefit from standard pharmacological therapy, some patients suffer from insufficient treatment response or medication intolerance. Novel treatment approaches are therefore necessary. OBJECTIVE: Given the overlap between RLS and pain syndromes in both pathophysiological mechanisms and certain treatment options, we aimed to perform a scoping review of the available evidence on spinal cord stimulation (SCS) for RLS and discuss potential mechanistic implications. METHODS: We identified a total of 16 cases of patients with RLS who underwent SCS, all from case reports or case series. DISCUSSION: The published evidence is insufficient to assess SCS efficacy in patients with RLS, but SCS remains a promising investigational therapy in RLS on the basis of its potential mitigatory effects in the central hyperexcitability of the sensorimotor cortex through neuromodulation of spinal, subcortical, and cortical areas. A call for further research in this field is presented, with suggestions for future directions and trial designs.

Patient values and preferences regarding prognostic counseling in isolated REM sleep behavior disorder.

STUDY OBJECTIVES: Isolated REM sleep behavior disorder (iRBD) carries a high lifetime risk for phenoconversion to a defined neurodegenerative disease (NDD) including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. We aimed to examine iRBD patient values and preferences regarding prognostic counseling. METHODS: One hundred thirteen iRBD patient participants enrolled in the Mayo Clinic iRBD Patient Registry were sent an email survey concerning their values and preferences concerning NDD prognostic counseling and their experiences following diagnosis with iRBD. RESULTS: Of 81 respondents (71.7% response rate), the majority were men (74.0%) with an average age of 65.7 (±9.7) years. Responses indicated a strong preference toward receiving prognostic information about possible future NDD development. 92.5% of respondents felt knowledge concerning personal NDD risk was important, while 87.6% indicated prognostic discussions were important to maintaining trust in their physician. 95.7% indicated a desire for more information, while only 4.3% desired less information regarding their NDD prognostic risk. Most respondents strongly agreed that prognostic information was important to discuss with their family and friends and inform future life planning, and most expressed interest in learning more about future neuroprotective therapies and symptomatic treatments for parkinsonism and dementia. CONCLUSIONS: Most iRBD patients indicated strong preferences for disclosure of NDD prognostic risk and indicated that prognostic information was important for family discussions and future life planning. Future broader surveys and qualitative studies of clinic-based and ultimately community dwelling iRBD patients' values and preferences are needed to guide appropriately tailored and individualized prognostic counseling approaches following iRBD diagnosis.

Specialist approaches to prognostic counseling in isolated REM sleep behavior disorder.

OBJECTIVES/BACKGROUND: Most middle-aged and older adult patients with isolated (idiopathic) REM sleep behavior disorder (RBD) eventually develop parkinsonism, dementia with Lewy bodies, or multiple system atrophy. We aimed to describe the current sleep medicine specialist approach toward RBD prognostic counseling, and to determine physician beliefs and characteristics that impact provision of counseling. PATIENTS/METHODS: We surveyed 70 sleep medicine physicians with RBD expertise for demographic information, counseling practices, and their beliefs and understandings concerning the association between RBD and synucleinopathies, among other questions. Responses were summarized by descriptive statistics. RESULTS: Among the 44 respondents (63% response rate), 41 (93.2%) regularly provided prognostic counseling for most RBD patients, but only 31.8% routinely asked about patient preferences on receiving counseling. 41.8% believed that the risk for developing overt synucleinopathy following RBD diagnosis was >80%, but only 15.9% routinely provided this detailed phenoconversion risk estimate to their patients. Most respondents were concerned that RBD prognostic counseling could adversely impact on the patient's and family's mental health. CONCLUSIONS: Most expert RBD sleep clinicians routinely counsel their patients regarding the high risk for phenoconversion to parkinsonism or dementia, yet relatively few routinely ask patients about their preferences for receiving this information, and fewer provide details concerning the known high risk estimates for developing a synucleinopathy. Future research should analyze patients' values and preferences in RBD populations to inform approaches toward shared decision making for RBD prognostic counseling.

Physician and patient determinants of prognostic counseling in idiopathic REM sleep-behavior disorder.

OBJECTIVES/BACKGROUND: Prognostic counseling about the risk for developing overt neurodegenerative disorders for patients with idiopathic REM sleep-behavior disorder (iRBD) and isolated REM sleep without atonia (iRSWA) is difficult, given lack of disease-modifying interventions and uncertainty in accurate prognostication for individuals. We aimed to analyze patient and physician characteristics associated with documented prognostic discussions for patients with iRBD and iRSWA. PATIENTS/METHODS: We retrospectively reviewed the medical records for 138 (112 iRBD and 26 iRSWA) patients seen at the Mayo Clinic between 2012 and 2015. We analyzed physician and patient demographics, initial complaint, and other information discussed during office visits. We then comparatively analyzed the impact of physician and patient characteristics on documented prognostic discussions using Chi Square or Fischer's exact test. RESULTS: Mean iRBD patient age was 65.0 ± 13.0, and mean iRSWA age was 58 ± 15 years. Seventy-eight (69.6%) iRBD and 22 (84.6%) iRSWA patients were men. Sixty-two (55%) iRBD and three (12%) iRSWA patients received prognostic counseling about phenoconversion risk. iRBD was a secondary complaint in 67 (59.8%). Patients over age 60 years and those having iRBD as a chief complaint more frequently received prognostic discussions than those with opposite characteristics (all p < 0.05). Patient sex and antidepressant use were not associated with counseling. Sleep neurologists disclosed prognostic information most frequently, with male more likely than female clinicians to disclose prognoses. CONCLUSIONS: Several patient and physician characteristics appear to influence documented prognostic counseling for iRBD/RSWA patients. Future studies of iRBD/RSWA patients' preferences are needed to clarify ethically appropriate physician-patient communication concerning prognosis.

Perioperative risks of narcolepsy in patients undergoing general anesthesia: A case-control study.

STUDY OBJECTIVE: To compare the perioperative outcomes between patients with narcolepsy and matched controls undergoing anesthetic management. DESIGN: Retrospective 2:1 matched study design. SETTING: Large tertiary medical center. PATIENTS: Narcoleptic patients who underwent general anesthesia from January 1, 2011, through September 30, 2015, were matched with controls by age, sex, and type and year of surgery. MEASUREMENTS: Medical records were reviewed for episodes of respiratory depression during phase I recovery and for other meaningful perioperative outcomes. MAIN RESULTS: The perioperative courses of 76 narcoleptic patients and their controls were examined. Compared to controls, narcoleptic patients were more often prescribed central nervous system stimulants (73.7% vs 4.0%, P<0.001) and antidepressants (46.1% vs 27.6%, P=0.007) and more often had obstructive sleep apnea (40.8% vs 19.1%, P<0.001). The intraoperative course was similar. The number of episodes of respiratory depression was not different between patients and controls (5 [6.6%] vs 12 [7.9%], respectively; P=0.80). Narcoleptic patients had a higher frequency of emergency response team activations (5 of 76 [6.6%]; 95% CI, 2.2%-14.7%) compared to controls (2 of 152 [1.3%]; 95% CI, 0.2%-4.7%) (P=0.04). Hemodynamic instability was the indication for all emergency response team activations except 1, which was for a narcoleptic patient who had excessive postoperative sedation and respiratory depression. CONCLUSIONS: Narcoleptic patients had similar intraoperative courses as the matched controls, including phase I anesthetic recovery. However, they had a higher rate of emergency response team activations than the controls, which suggests that patients with narcolepsy may be at increased perioperative risk.

Neuroimaging-evident lesional pathology associated with REM sleep behavior disorder.

BACKGROUND/RATIONALE: Rapid eye movement (REM) sleep behavior disorder (RBD) is a potentially injurious parasomnia characterized by dream enactment behavior and polysomnographic REM sleep without atonia (RSWA). Recently, RBD not only has been shown to be strongly associated with synucleinopathy neurodegeneration but has also been rarely reported to be associated with structural lesions involving the brainstem or limbic system. The aim of this study was to describe the clinical, neuroimaging, and outcome characteristics in a case series of patients with lesional RBD. METHODS: This is a retrospective case series from a tertiary care referral center. RESULTS: A total of 10 patients with lesional RBD were identified. Seven (70%) were men, with an average age of sleep symptom onset of 53.7 ± 17.0 years. Structural pathology evident on neuroimaging included four extraaxial (three meningiomas and one basilar fusiform aneurysm with brainstem compression) and six intraaxial (encephalomalacia, multiple sclerosis, vasculitis, autoimmune limbic encephalitis, and leukodystrophy) lesions. No patient developed parkinsonian features or cognitive impairment suggestive of synucleinopathy over an average of 45.4 ± 35.2 months of follow-up. CONCLUSIONS: RBD is rarely associated with non-synuclein structural lesions affecting the pons, medulla, or limbic system. The spectrum of lesional RBD comprises tumors, aneurysms, leukodystrophy, and autoimmune/inflammatory/demyelinating brain lesions.

DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients.

OBJECTIVE: To describe the detection frequency and clinical associations of immunoglobulin G (IgG) targeting dipeptidyl-peptidase-like protein-6 (DPPX), a regulatory subunit of neuronal Kv4.2 potassium channels. METHODS: Specimens from 20 patients evaluated on a service basis by tissue-based immunofluorescence yielded a synaptic immunostaining pattern consistent with DPPX-IgG (serum, 20; CSF, all 7 available). Transfected HEK293 cell-based assay confirmed DPPX specificity in all specimens. Sixty-nine patients with stiff-person syndrome and related disorders were also evaluated by DPPX-IgG cell-based assay. RESULTS: Of 20 seropositive patients, 12 were men; median symptom onset age was 53 years (range, 13-75). Symptom onset was insidious in 15 and subacute in 5. Twelve patients reported prodromal weight loss. Neurologic disorders were multifocal. All had one or more brain or brainstem manifestations: amnesia (16), delirium (8), psychosis (4), depression (4), seizures (2), and brainstem disorders (15; eye movement disturbances [8], ataxia [7], dysphagia [6], dysarthria [4], respiratory failure [3]). Nine patients reported sleep disturbance. Manifestations of central hyperexcitability included myoclonus (8), exaggerated startle (6), diffuse rigidity (6), and hyperreflexia (6). Dysautonomia involved the gastrointestinal tract (9; diarrhea [6], gastroparesis, and constipation [3]), bladder (7), cardiac conduction system (3), and thermoregulation (1). Two patients had B-cell neoplasms: gastrointestinal lymphoma (1), and chronic lymphocytic leukemia (1). Substantial neurologic improvements followed immunotherapy in 7 of 11 patients with available treatment data. DPPX-IgG was not detected in any of the stiff-person syndrome patients. CONCLUSIONS: DPPX-IgG is a biomarker for an immunotherapy-responsive multifocal neurologic disorder of the central and autonomic nervous systems.

Factors associated with injury in REM sleep behavior disorder.

OBJECTIVE: As factors associated with injury in rapid eye movement (REM) sleep behavior disorder (RBD) remain largely unknown, we aimed to identify such factors. METHODS: We surveyed consecutive idiopathic (iRBD) or symptomatic RBD patients seen between 2008 and 2010 regarding RBD-related injuries. Associations between injuries and clinical variables were determined with odds ratios (OR) and multiple logistic regression analyses. The primary outcome variables were injury and injury severity. RESULTS: Fifty-three patients (40%) responded. Median age was 69 years, and 35 (73.5%) were men. Twenty-eight (55%) had iRBD. Twenty-nine (55%) reported injury, with 37.8% to self and 16.7% to the bed partner. 11.3% had marked injuries requiring medical intervention or hospitalization, including two (4%) subdural hematomas. iRBD diagnosis (OR = 6.8, p = 0.016) and dream recall (OR = 7.5, p = 0.03) were associated with injury; and iRBD diagnosis was independently associated with injury and injury severity adjusting for age, gender, DEB frequency, and duration. Falls (p = 0.03) were also associated with injury severity. DEB frequency was not associated with injury, injury severity, or falls. CONCLUSIONS: Injuries appear to be a frequent complication of RBD, although the relatively low response rate in our survey could have biased results. iRBD patients are more likely to suffer injury--and more severe injuries--than symptomatic RBD patients. In addition, recall of dreams was also associated with injury, and dream enactment behavior (DEB)-related falls were associated with more severe injuries. One in nine patients suffered injury requiring medical intervention. The frequency of DEB did not predict RBD-related injuries, highlighting the importance of timely initiation of treatment for RBD in patients having even rare DEB episodes. Future prospective studies will be necessary to define predictors of injury in RBD.

Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in a community-based sample.

OBJECTIVE: To validate a questionnaire focused on REM sleep behavior disorder (RBD) in a community-based sample. BACKGROUND: RBD is a parasomnia manifested by recurrent dream enactment behavior during REM sleep. While confirmation of RBD requires the presence of REM sleep without atonia on polysomnography (PSG), a screening measure for RBD validated in older adults would be desirable for clinical and research purposes. METHODS: We had previously developed the Mayo Sleep Questionnaire (MSQ) to screen for the presence of RBD and other sleep disorders. We assessed the validity of the MSQ by comparing the responses of subjects' bed partners with the findings on PSG. All subjects recruited from 10/04 to 12/08 in the Mayo Clinic Study of Aging--a population-based study of aging in Olmsted County, Minnesota--who had also undergone a previous PSG were the focus of this analysis. RESULTS: The study sample included 128 subjects (104 male; median age 77 years [range 67-90]), with the following clinical diagnoses at baseline assessment: normal (n = 95), mild cognitive impairment (n = 30), and mild Alzheimer disease (n = 3). Nine (5%) subjects had RBD based on history and PSG evidence of REM sleep without atonia. The core question on recurrent dream enactment behavior yielded sensitivity (SN) of 100% and specificity (SP) of 95% for the diagnosis of RBD. The profile of responses on four additional subquestions on RBD improved specificity. CONCLUSIONS: These data suggest that the MSQ has adequate SN and SP for the diagnosis of RBD among elderly subjects in a community-based sample.

Treatment outcomes in REM sleep behavior disorder.

OBJECTIVE: REM sleep behavior disorder (RBD) is usually characterized by potentially injurious dream enactment behaviors (DEB). RBD treatment aims to reduce DEBs and prevent injury, but outcomes require further elucidation. We surveyed RBD patients to describe longitudinal treatment outcomes with melatonin and clonazepam. METHODS: We surveyed and reviewed records of consecutive RBD patients seen at Mayo Clinic between 2008-2010 to describe RBD-related injury frequency-severity as well as RBD visual analog scale (VAS) ratings, medication dosage, and side effects. Statistical analyses were performed with appropriate non-parametric matched pairs tests before and after treatment, and with comparative group analyses for continuous and categorical variables between treatment groups. The primary outcome variables were RBD VAS ratings and injury frequency. RESULTS: Forty-five (84.9%) of 53 respondent surveys were analyzed. Mean age was 65.8 years and 35 (77.8%) patients were men. Neurodegenerative disorders were seen in 24 (53%) patients and 25 (56%) received antidepressants. Twenty-five patients received melatonin, 18 received clonazepam, and two received both as initial treatment. Before treatment, 27 patients (60%) reported an RBD associated injury. Median dosages were melatonin 6 mg and clonazepam 0.5 mg. RBD VAS ratings were significantly improved following both treatments (p(m) = 0.0001, p(c) = 0.0005). Melatonin-treated patients reported significantly reduced injuries (p(m) = 0.001, p(c) = 0.06) and fewer adverse effects (p = 0.07). Mean durations of treatment were no different between groups (for clonazepam 53.9 ± 29.5 months, and for melatonin 27.4 ± 24 months, p = 0.13) and there were no differences in treatment retention, with 28% of melatonin and 22% of clonazepam-treated patients discontinuing treatment (p = 0.43). CONCLUSIONS: Melatonin and clonazepam were each reported to reduce RBD behaviors and injuries and appeared comparably effective in our naturalistic practice experience. Melatonin-treated patients reported less frequent adverse effects than those treated with clonazepam. More effective treatments that would eliminate injury potential and evidence-based treatment outcomes from prospective clinical trials for RBD are needed.

Characteristics of REM sleep behavior disorder in childhood.

STUDY OBJECTIVE: To describe our experience regarding the clinical and polysomnographic features of REM sleep behavior disorder (RBD) in childhood. METHODS: This was a retrospective chart review of children and adolescents with RBD and REM sleep without atonia. Demographics, and clinical and polysomnographic information were tabulated. Our findings were compared with those in the existing literature. RESULTS: The 15 subjects identified (13 RBD and 2 having REM sleep without atonia) had a mean age at diagnosis of 9.5 years (range 3-17 years); 11/15 (73%) were male. Nightmares were reported in 13/15 and excessive daytime sleepiness in 6/15. Two children had caused bodily harm to bedmate siblings. Comorbidities, which were multiple in some subjects, included anxiety (8/15), attention deficit disorder (10/15), nonspecific developmental delay (6/15), Smith-Magenis syndrome (1/15), pervasive developmental disorder (1/15), narcolepsy (1/15), idiopathic hypersomnia (1/15), and Moebius Syndrome (1/15). Abnormal MRI scans were seen in 5/8 evaluated subjects. Treatments consisted of clonazepam (10/15), melatonin (2/15), and discontinuation of a tricyclic agent (1/15), with a favorable response in 11 of 13. Two of 15 patients with REM sleep without atonia did not require pharmacotherapy. CONCLUSIONS: RBD in children may be associated with neurodevelopmental disabilities, narcolepsy, or medication use. It seems to be modestly responsive to benzodiazepines or melatonin. The etiology is distinct from that of common childhood arousal parasomnias and RBD in adults; congenital and neurodevelopmental disorders, medication effect, and narcolepsy coexisted in some, but none had an extrapyramidal neurodegenerative disorder.

Nocturnal moaning and groaning-catathrenia or nocturnal vocalizations.

PURPOSE: Descriptions of nocturnal vocalizations, including catathrenia, are few. We undertook a study at our center on patients diagnosed with catathrenia, to evaluate the characteristic features of these events and their response to continuous positive airway pressure (CPAP) treatment. METHODS: Retrospective study of patients with a diagnosis of catathrenia who had an overnight polysomnogram (PSG) and available synchronized audio video recordings (to confirm the presence of moaning and groaning), at our center between January 2007 and May 2010. RESULT: Ten patients were included in the analysis. Three (30%) patients presented with the chief complaint of expiratory noises during sleep. The other moaning/groaning sounds were incidental findings noted by the sleep technologist and/or the sleep physician. The number of moaning/groaning events during PSG varied between 2 and 343 per patient with sound duration ranging from 0.4 to 21.4 s. Moaning/groaning events during exhalation (1,026 episodes) were separated into typical catathrenia events (as per the International Classification of Sleep Disorders, 2nd edition [ICSD-2] definition) and atypical/nocturnal vocalization events (moaning/groaning events that did not meet the ICSD-2 criteria). Typical catathrenia events (5% or 52/1,026) were experienced by five of the ten patients and had mean exhalation duration of 14.97 ± 5.13 s (range 5.8-24 s) with a mean sound duration of 8.47 ± 5.97 s (range 2-21.4 s). The typical and atypical events occurred predominantly in NREM sleep. Six of the ten patients had associated sleep-disordered breathing and four underwent CPAP titration. All four patients had significantly fewer events of moaning/groaning (mean reduction was 75.8 ± 26.2%) with CPAP. CONCLUSION: New and unique features were identified in our series of patients diagnosed with catathrenia. Though all events had the characteristic moaning and groaning sound during exhalation, only a small percentage (5%) met the catathrenia definition as outlined in ICSD-2. Do we label the atypical events as part of the spectrum of nocturnal vocalizations or consider them as catathrenia by redefining the criteria? CPAP appeared to be a reasonable treatment option.

Sleep manifestations of voltage-gated potassium channel complex autoimmunity.

OBJECTIVE: To identify the spectrum of sleep disorders associated with autoantibodies reactive with voltage-gated potassium channel (VGKC) complexes. DESIGN: Case series of all patients with neurologic disorders of VGKC autoimmunity evaluated in the Mayo Clinic Center for Sleep Medicine (Rochester, Minnesota) between January 1, 1994, and February 1, 2010. SETTING: Academic referral center. PATIENTS: Fifteen consecutive patients were identified with limbic encephalitis (n = 5), Morvan syndrome (n = 4), and overlapping features (n = 6). INTERVENTION: Ten patients received immunotherapy (corticosteroids, cyclophosphamide, or mycophenolate mofetil). MAIN OUTCOME MEASURE: Response to immunotherapy. RESULTS: The median VGKC autoantibody value at presentation was 1.51 nmol/L (range, 0.09-4.86 nmol/L). Neoplasms were discovered in 5 patients (33%) (thymoma [n = 2], prostate adenocarcinoma, colon adenocarcinoma, and melanoma). In 14 patients (93%), serious sleep disturbances were identified (insomnia, dream enactment behavior, suspected nocturnal epilepsy, and hypersomnia). Severe insomnia occurred in 9 patients (60%), regardless of neurologic presentation. Polysomnography at presentation (7 patients) revealed a mean sleep efficiency of 19% (4 patients had complete absence of sleep). Dream enactment behavior occurred in 8 patients (53%), including 3 of 5 with limbic encephalitis and all 4 with Morvan syndrome. Two of 7 polysomnograms demonstrated loss of rapid eye movement sleep muscle atonia; absent or minimal rapid eye movement sleep precluded interpretation in 4 patients. Sleep disorders resolved completely or almost completely in 8 of 10 patients who received immunotherapy. CONCLUSIONS: Sleep disorders are cardinal manifestations of VGKC complex autoimmunity in association with a spectrum of neurologic presentations. They may respond favorably to immunotherapy.

Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in an aging and dementia cohort.

OBJECTIVE: To validate a questionnaire focused on rapid eye movement sleep (REM) sleep behavior disorder (RBD) among participants in an aging and dementia cohort. BACKGROUND: RBD is a parasomnia that can develop in otherwise neurologically-normal adults as well as in those with a neurodegenerative disease. Confirmation of RBD requires polysomnography (PSG). A simple screening measure for RBD is desirable for clinical and research purposes. METHODS: We had previously developed the Mayo Sleep Questionnaire (MSQ), a 16 item measure, to screen for the presence of RBD and other sleep disorders. We assessed the validity of the MSQ by comparing the responses of patients' bed partners with the findings on PSG. All subjects recruited in the Mayo Alzheimer's Disease Research Center at Mayo Clinic Rochester and Mayo Clinic Jacksonville from 1/00 to 7/08 who had also undergone a PSG were the focus of this analysis. RESULTS: The study sample was comprised of 176 subjects (150 male; median age 71 years (range 39-90)), with the following clinical diagnoses: normal (n = 8), mild cognitive impairment (n = 44), Alzheimer's disease (n = 23), dementia with Lewy bodies (n = 74), as well as other dementia and/or parkinsonian syndromes (n = 27). The core question on recurrent dream enactment behavior yielded a sensitivity (SN) of 98% and specificity (SP) of 74% for the diagnosis of RBD. The profile of responses on four additional subquestions on RBD and one on obstructive sleep apnea improved specificity. CONCLUSIONS: These data suggest that among aged subjects with cognitive impairment and/or parkinsonism, the MSQ has adequate SN and SP for the diagnosis of RBD. The utility of this scale in other patient populations will require further study.

Impulse control disorders with the use of dopaminergic agents in restless legs syndrome: a case-control study.

STUDY OBJECTIVES: To determine the frequency of impulse control disorders (ICDs) with the use of dopaminergic agents in restless legs syndrome (RLS). DESIGN: Prospective case-control study using a screening questionnaire for ICDs, followed by phone interview to confirm diagnoses for those meeting preset scoring thresholds on the questionnaire. SETTING: Academic, comprehensive sleep medicine center. PATIENTS OR PARTICIPANTS: (1) One hundred patients with RLS treated with dopaminergic agents, (2) 275 patients with obstructive sleep apnea (OSA) without RLS or exposure to dopaminergic agents; and (3) 52 patients with RLS who were never treated with dopaminergic agents. Subjects with parkinsonism were excluded. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS: Based on the questionnaire, frequencies of ICDs for the RLS treatment group were 10% compulsive shopping, 7% pathologic gambling, 23% compulsive eating, 8% hypersexuality, and 10% punding. These values were statistically significant when compared with control subjects with OSA for compulsive shopping and pathologic gambling. With additional information from the phone interview, adjusted frequencies for the RLS treatment group were 9% compulsive shopping, 5% pathologic gambling, 11% compulsive eating, 3% hypersexuality, 7% punding, and 17% any ICD. These values were statistically significant when compared with those of control subjects with OSA for compulsive shopping, pathologic gambling, punding, and any ICD, as well as for compulsive shopping when compared with control subjects with RLS who were not treated with dopaminergic agents. In the RLS treatment group, a statistically significant dose effect was found for pramipexole in those subjects confirmed to have ICDs by both the questionnaire and phone interview. Mean duration of treatment at ICD onset was 9.5 months. CONCLUSIONS: ICDs are common with the use of dopaminergic agents for treatment of RLS. Given the potentially devastating psychosocial consequences of these behaviors, it is critical to actively screen for ICDs in this population.

Effects of continuous positive airway pressure on stridor in multiple system atrophy-sleep laryngoscopy.

The presence of stridor in patients with multiple system atrophy (MSA) is associated with poor prognosis, mainly due to a high risk of complete airway obstruction at night. Continuous positive airway pressure (CPAP) therapy has been proposed as a treatment of MSA-associated stridor, but, until now, there has been no visual documentation of the effect of CPAP on laryngeal patency during nonpharmacologically induced spontaneous sleep of a patient with MSA. We present a video-laryngoscopic documentation of a 57-year-old woman with MSA who was evaluated for nocturnal stridor. Direct laryngoscopy during sleep without pharmacologic sedation documented inspiratory adduction of the vocal cords with downward displacement of the larynx. Application of CPAP resulted in improvement of stridor, distension of the hypopharynx, abduction of vocal cords, and reduction of the downward displacement of the larynx. We discuss the possible mechanisms of action of CPAP in MSA-associated stridor.

Idiopathic rapid-eye-movement sleep disorder: associations with antidepressants, psychiatric diagnoses, and other factors, in relation to age of onset.

BACKGROUND: A retrospective, case-control chart review was performed to examine the relationship between the age of onset of idiopathic RBD and secondary associations. METHODS: Forty-eight idiopathic RBD patients were divided into early-onset and late-onset groups, compared to each other, and to their respective non-RBD controls. RESULTS: There were more females in the early-onset group as compared to their older counterparts (45% vs. 11%, p=0.007). Early-onset patients also had significantly more past and present psychiatric diagnoses [85% (both categories) vs. 46% and 36%, respectively, p<0.01 for both comparisons] and antidepressant use (80% vs. 46%, p=0.02) than the late-onset group. In comparison to non-RBD controls, early-onset patients again exhibited more psychiatric diagnoses (odds ratio=17.0 [3.5-83.4], equivalent for past and present diagnoses) and antidepressant use (odds ratio=12.0 [2.7-53.3]). Late-onset patients also had a higher frequency of past (odds ratio=7.2 [1.8-29.6]) and present (odds ratio=4.6 [1.1-19.3]) psychiatric diagnoses as compared to their non-RBD controls, but did not demonstrate a statistically significant difference in antidepressant use. There were otherwise no significant intergroup or intragroup differences with respect to the other assessed variables. CONCLUSIONS: Although causality cannot be inferred, numerous implications can be entertained, particularly in the early-onset group, including direct or indirect correlations with medication use and/or psychopathology and the development of RBD. The relatively high number of females in the early-onset group suggests a unique clinical profile for a condition typically characterized as male-predominant.

Ornithine transcarbamylase deficiency presenting as encephalopathy during adulthood following bariatric surgery.

BACKGROUND: Neurological complications following bariatric surgery are rare. Whereas nutritional deficiencies are the most common cause of neurological symptoms, the unmasking of previously subclinical metabolic disorders can also lead to significant morbidity. OBJECTIVE: To characterize the clinical presentation, serum biochemical fluctuations, and functional enzymatic analysis of a case of functional ornithine transcarbamylase deficiency unmasked by a dietary change following bariatric surgery. DESIGN: Case report. SETTING: Tertiary referral center, hospital (inpatient) setting. PATIENT: A 29-year-old woman who presented with intermittent encephalopathy associated with recurrent hyperammonemia. INTERVENTIONS: Clinical, biochemical, and mutational studies. RESULTS: The pattern of intermittent hyperammonemia and encephalopathy following oral and parenteral nutrition suggested a urea cycle abnormality. Functional enzymatic assay results showed markedly reduced ornithine transcarbamylase activity in the absence of known coding mutations. CONCLUSION: Previously asymptomatic ornithine transcarbamylase deficiency should be suspected in adult patients who develop recurrent hyperammonemia and encephalopathy following bariatric surgery.