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.

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.

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.

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.