Stress and Neurological Disease Management

Stress is an omnipresent force in our everyday lives. Its role is to help us overcome challenges, whether they are working around the clock or fighting a disease. However, way too often stress response spins out of control and no longer does us a service. Clinicians, caregivers, and especially patients are exposed to high levels of stress. On one hand, living with an illness and going through a lengthy recovery process gives rise to anxiety, sadness, depression, and ultimately, chronic stress. On the other hand, stress as a pathological response to changes in the brain environment may accompany a disease but remain outside the realm of consciousness. Both types of stress response are detrimental and require management. How exactly does stress influence neurological disease progression, and how can stress be managed?

The best-known targets of stress are the cardiovascular, immune, and nervous systems. The link between psychological stress and cardiovascular disease has long been established. A multitude of factors that affect stress level, such as personality and occupation, are linked to an increased risk of stroke. Hence, stress reduction techniques may be recommended in people at risk of stroke, in addition to the staples of stroke prevention, high blood pressure- and cholesterol-lowering medications. Patients at risk of both primary and secondary stroke could benefit from stress-lowering interventions. For example, in black patients with coronary heart disease, mindfulness techniques aimed to reduce stress (transcendental meditation) lower the risk of secondary stroke by 48% (hazard ratio, 0.52; 95% confidence interval (CI), 0.29 - 0.92; P = 0.025).¹

Psychogenic stress described above is just one of the triggers of cardiovascular disease; acute neurogenic stress is another. Neurogenic stress is defined by excessive release of catecholamines from sympathetic nerve terminals into the myocardium, release of catecholamines into the systemic circulation, and heightened sensitivity to norepinephrine.² The described pathological events in patients with brain damage result in a syndrome known as neurogenic stress cardiomyopathy. Neurogenic stress may develop in response to brain damage, eg, traumatic injury, subarachnoid hemorrhage, epilepsy, and ischemic or hemorrhagic stroke. Several brain regions are implicated into sympathetic cardiovascular response: hypothalamus, amygdala, and various cortical regions such as insula and cingulate gyrus. Damage to these regions sets neurogenic stress response in motion. The amygdala, which controls fear conditioning, may produce a maladaptive psychological response when damaged, making managing stress response in these patients more difficult.

In patients with brain damage, both types of stress, acute neurogenic and chronic psychogenic, require management. In the acute phase of brain injury, it’s important to maintain homeostasis, so heart function must be closely monitored. Several approaches to diagnosing neurogenic cardiomyopathy exist: monitoring of plasma and urine catecholamine levels and assessment of cardiac function with electrocardiography and echocardiography, among others. Identification of people most at risk of neurogenic stress cardiomyopathy may also be beneficial and is currently a focus of research. Treatment of neurogenic stress cardiomyopathy is largely symptomatic and supportive; it includes β-blockers and several experimental approaches.²

Stress following brain injury may take a chronic form. According to a recent study by Marina and colleagues, at 3 month post injury, the hormonal system was still out of balance: thyroid and gonadal hormones were reduced and stress hormones were elevated in 32% and 68% of the patients, which in turn affected their ability to live independently at 1 year post injury.³ In some patients, posttraumatic stress disorder (PTSD) may develop. A recent review identified two trauma-focused interventions, cognitive processing therapy and prolonged exposure therapy, as the most efficacious in military personnel and veterans with PTSD.⁴

Unmanaged stress also negatively impacts memory. Dementia, particularly Alzheimer disease, is much more common in PTSD sufferers. Stress has recently been shown to trigger degeneration of dopaminergic neurons, which causes Parkinson disease (PD) in chronically restrained rats.⁵ Taken together, these findings accentuate the importance of stress management in patients with brain trauma and neurodegenerative disorders. A recent study aimed to identify the main gaps in PD management, which are a priority in PD research, listed stress and anxiety management as the second most important area of research.⁶

Another example of disease that is exacerbated by stress is multiple sclerosis (MS).

New Gd-enhancing MS lesions tend to appear 4-8 weeks after a stressful experience.⁷ Stress management helps improve wellbeing and disease outcomes in patients with MS. According to recent literature, cognitive behavioral therapy is the most commonly used and highly effective intervention for stress in MS patients.^8,9

Regardless of its source and mechanism, stress has a diverse detrimental effect in patients with neurological conditions. Patients as well as clinicians and caregivers should be aware of the negative effects of stress on disease progression, should be able to recognize signs of stress, and should consider stress management interventions as a part of overall disease management strategy.

References:

1. Schneider RH, et al. Stress reduction in the secondary prevention of cardiovascular disease: randomized, controlled trial of transcendental meditation and health education in blacks. Circ Cardiovasc Qual Outcomes. 2012;5(6):750-758.

2. Mazzeo AT, et al. Brain-heart crosstalk: the many faces of stress-related cardiomyopathy syndromes in anaesthesia and intensive care. Br J Anaesth. 2014;112(5):803-815.

3. Marina D, et al. Early endocrine alterations reflect prolonged stress and relate to 1-year functional outcome in patients with severe brain injury. Eur J Endocrinol. 2015;172(6):813-822.

4. Steenkamp MM, et al. Psychotherapy for military-related PTSD: a review of randomized clinical trials. JAMA. 2015;314(5):489-500.

5. Sugama S, et al. Chronic restraint stress triggers dopaminergic and noradrenergic neurodegeneration: possible role of chronic stress in the onset of Parkinson's disease. Brain Behav Immun. 2015 Aug 17. [Epub ahead of print]

6. Deane KH, et al. Priority setting partnership to identify the top 10 research priorities for the management of Parkinson's disease. BMJ Open. 2014 Dec 14;4(12):e006434.

7. Mohr DC, et al. Association between stressful life events and exacerbation in multiple sclerosis: a meta-analysis. BMJ. 2004;328(7442):731.

8. Reynard AK, et al. A systematic review of stress-management interventions for multiple sclerosis patients. Int J MS Care. 2014;16(3):140-144.

9. Mohr DC, et al. A randomized trial of stress management for the prevention of new brain lesions in MS. Neurology. 2012;79(5):412-419.