Hypocapnic cerebral hypoperfusion: A biomarker of orthostatic intolerance

Abstract:

The objective of the study was to identify markers of hypocapnic cerebral hypoperfusion (HYCH) in patients with orthostatic intolerance (OI) without tachycardia and without orthostatic hypotension. This single center, retrospective study included OI patients referred for autonomic evaluation with the 10 min tilt test. Heart rate, end-tidal CO2 (ET-CO2), blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery were monitored. HYCH was defined by: (1) Symptoms of OI; (2) Orthostatic hypocapnia (low ET-CO2); (3) Abnormal decline in orthostatic CBFv due to hypocapnia; 4) Absence of tachycardia, orthostatic hypotension, or other causes of low CBFv or hypocapnia.

Sixteen subjects met HYCH criteria (15/1 women/men, age 38.5±8.0 years) and were matched by age and gender to postural tachycardia patients (POTS, n = 16) and healthy controls (n = 16). During the tilt, CBFv decreased more in HYCH (-22.4±7.7%, p<0.0001) and POTS (-19.0±10.3%, p<0.0001) compared to controls (-3.0±5.0%). Orthostatic ET-CO2 was lower in HYCH (26.4±4.2 (mmHg), p<0.0001) and POTS (28.6±4.3, p<0.0001) compared to controls (36.9 ± 2.1 mmHg). Orthostatic heart rate was normal in HYCH (89.0±10.9 (BPM), p<0.08) and controls (80.8 ±11.2), but was higher in POTS (123.7±11.2, p<0.0001). Blood pressure was normal and similar in all groups.

It is concluded that both HYCH and POTS patients have comparable decrease in CBFv which is due to vasoconstrictive effect of hypocapnia. Blood flow velocity monitoring can provide an objective biomarker for HYCH in OI patients without tachycardia.

Source: Novak P. Hypocapnic cerebral hypoperfusion: A biomarker of orthostatic intolerance. PLoS One. 2018 Sep 26;13(9):e0204419. doi: 10.1371/journal.pone.0204419. PMID: 30256820; PMCID: PMC6157889. https://pmc.ncbi.nlm.nih.gov/articles/PMC6157889/ (Full text)

Expanded autonomic testing helps to pinpoint cases of orthostatic intolerance

News:

Using expanded, state-of-the-art capabilities in autonomic testing, Peter Novak, MD, PhD, Chief of the Division of Autonomic Neurology in the Department of Neurology, is driving better understanding of hard-to-diagnose patients with orthostatic intolerance.

The debilitating condition is among the most common neurological conditions affecting women in the United States ages 35 or younger. While knowledge of orthostatic intolerance has become more nuanced in recent years, diagnosing some patients’ symptoms when changing from lying to standing (dizziness, weakness and shortness of breath, with or without rapid heartbeat) has remained elusive.

The identification of postural orthostatic tachycardia syndrome (POTS) in the early 1990s led to clearer diagnosis of many patients. But the syndrome, by definition, excludes those who do not experience tachycardia. To address their symptoms, these patients sometimes are prescribed antianxiety or antidepressant medications.

To better understand these patients, Dr. Novak turned to continuous monitoring of end tidal CO2 and CBFv (cerebral blood flow velocity). As the technologies became available for clinical use, Novak added them to routine testing. The results led him to identify two new syndromes relating to orthostatic dizziness.

“We can now diagnose people who were previously thought to have psychiatric illness or had no diagnosis at all,” says Dr. Novak, of the Department of Neurology, one of only a few departments in the United States that has a Division of Autonomic Neurology.

In addition to continuous monitoring of heart rate and blood pressure that is standard for Valsalva maneuver and tilt-table tests, Dr. Novak’s Autonomic Testing Lab, located at Brigham and Women’s Faulkner Hospital, also measures and interprets end tidal CO2 and CBFv during these tests. Through testing, he has characterized two new syndromes:

  • Hypocapnic cerebral hypoperfusion (HYCH) is a novel syndrome of low CBFv that Novak described in late 2018 in PLoS ONE, as a biomarker of orthostatic intolerance. HYCH can be detected during a tilt test, in patients without orthostatic tachycardia, hypotension, arrhythmia, vascular abnormalities or other causes of abnormal orthostatic CBFv. “This is POTS without the T,” explains Dr. Novak. “These people have normal BP and normal heart rate. But they have the same low blood flow as in POTS due to vasoconstrictive effect of hypocapnia (low end tidal CO2). This is the main reason to monitor blood flow. Otherwise you can miss what is going on with this the patient, and the patient could be misdiagnosed as having a psychiatric illness.” The Autonomic Testing Lab currently sees at last two patients each month who meet the criteria of HYCH. Treatment is similar to that of patients with POTS (combination of exercise, diet and medication for more severe cases), since HYCH and POTS are probably on a spectrum of the same disorder.
  • Orthostatic Cerebral Hypoperfusion Syndrome (OCHOS) is a syndrome of orthostatic intolerance associated with low CBFv that Dr. Novak first described in 2016. In this syndrome, the orthostatic cerebral blood flow is reduced while all other variables are normal. OCHOS can be disabling. Many patients respond to volume expansion or cerebral vasodilators, but the optimal therapy has yet to be found.

Both OCHOS and HYCH are described among the 100 case studies in Dr. Novak’s recently published book Autonomic Testing, (Oxford University Press, April 2019), intended as a practical manual for performing and interpreting autonomic testing. Each case study includes the testing evaluation, results (with visual images to guide test interpretations) and recommendations for treatment and follow-up. Nearly all cases show results of the newer techniques of continuous CBFv and CO2 monitoring concurrent with traditional heart rate and blood pressure testing. “Together, they are more valuable than separately,” Dr. Novak explains.

The combination of classic autonomic tests (Valsalva maneuver, deep breathing and tilt test) enhanced by using of continuous CBFv and CO2 monitoring together make up “the Brigham Protocol.” In addition, the protocol includes non-invasive skin biopsies, now routinely performed in the lab to assess direct small fiber damage, which may indicate inflammation that is treatable. “We call it autonomic testing, but it is more than that at our institution,” says Dr. Novak.

Since 2015, the Autonomic Testing Lab has performed autonomic testing on approximately 1,300 people, about half of them for orthostatic symptoms, says Dr. Novak.

For questions about autonomic testing or if you have a patient who would benefit from autonomic testing, learn more here.