Faculty Bibliography

It is now well recognized that there is a premotor phase of Parkinson's disease (PD) with hyposmia and REM sleep behavior disorder caused by degeneration of specific CNS neurons. Most patients with PD describe autonomic symptoms at the time of diagnosis suggesting that these features may have potential sensitivity as clinical biomarkers of the premotor phase. The recognition that damage to peripheral autonomic neurons is present in the early stages of PD has led to a search for specific abnormalities in autonomic function that could serve as predictive biomarkers. There is evidence that constipation, urinary and sexual dysfunction and more recently decreased cardiac chronotropic response during exercise, are part of the premotor parkinsonian phenotype. The sensitivity and specificity of these features has yet to be accurately assessed. We briefly review the evidence for autonomic dysfunction as biomarker of premotor PD.

OBJECTIVE: To assess autonomic function by heart rate variability (HRV) during sleep in patients with sleep related alveolar hypoventilation (SRAH) and to compare it with that of patients with obstructive sleep apnea (OSA) and control patients. DESIGN: Cross-sectional study. SETTING: Sleep Unit, University Hospital of University of Navarra. PATIENTS: Fifteen idiopathic and obesity related-SRAH patients were studied. For each patient with SRAH, a patient with OSA, matched in age, sex, body mass index (BMI), minimal oxygen saturation (SatO2), and mean SatO2 was selected. Control patients were also matched in age, sex, and BMI with patients with OSA and those with SRAH, and in apnea/hypopnea index (AHI) with patients with SRAH. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Time- and frequency-domain HRV measures (R-R, standard deviation of normal-to-normal RR interval [SDNN], very low frequency [VLF], low frequency [LF], high frequency [HF], LF/HF ratio) were calculated across all sleep stages as well as during wakefulness just before and after sleep during a 1-night polysomnography. In patients with SRAH and OSA, LF was increased during rapid eye movement (REM) when compared with control patients, whereas HF was decreased during REM and N1-N2 sleep stages. The LF/HF ratio was equally increased in patients with SRAH and OSA during REM and N1-N2. Correlation analysis showed that LF and HF values during REM sleep were correlated with minimal SatO2 and mean SatO2. CONCLUSIONS: Patients with SRAH exhibited an abnormal cardiac tone during sleep. This fact appears to be related to the severity of nocturnal oxygen desaturation. Moreover, there were no differences between OSA and SRAH, supporting the hypothesis that autonomic changes in OSA are primarily related to a reduced nocturnal oxygen saturation, rather than a consequence of other factors such as nocturnal respiratory events.

A 77-year-old woman with multiple myeloma for 5 years presented with obtundation, drowsiness, and disorientation over 15 days. Complete blood count revealed thrombocytopenia (25,000/microL). A brain CT disclosed multiple extraaxial hyperdense foci without bone destruction. Differential diagnosis included tumors (meningiomas, leukemia), subdural hematomas, and intracranial hemorrhages; the lesion's multiplicity and morphology were consistent with intracranial extramedullary hematopoiesis (IEH) (figure). Despite platelet transfusions, she died 2 days later of alveolar hemorrhage. Autopsy confirmed IEH and excluded erythropoiesis, reported in subdural hematomas. The formation of blood cells outside the bone marrow is usually related to anemia or lymphoproliferative disorders and is uncommon in multiple myeloma.(1) IEH can cause seizures, hydrocephalus, or cognitive changes.(2.)

The objective of this study was to assess cardiovascular response during cardiac stress testing in neurologically asymptomatic individuals who developed motor features of Parkinson's disease several years after the cardiac stress testing. This was a retrospective cohort study of patients who underwent cardiac stress testing between January 2001 and December 2010. Patients were followed until May 2012 to select those who developed Parkinson's disease. Heart rate and blood pressure both at rest and at peak exercise and heart rate variability at rest were recorded. For each patient who developed Parkinson's disease, 2 matched controls who did not develop Parkinson's disease at the end of the follow-up period were selected. Patients who were diagnosed with Parkinson's disease the same day of cardiac stress testing also were selected for comparison purposes. After excluding participants who were lost to follow-up, 2739 patients remained. From this cohort, 18 (11 men) had developed Parkinson's disease 4.27 +/- 2.56 years after the cardiac stress test. Thirty-six matched controls were selected. At peak exercise, the maximum heart rate and the percentage of theoretical maximum heart rate were significantly lower in patients who developed Parkinson's disease after cardiac stress testing compared with controls. The sensitivity of a maximum heart rate