Blood flow and white matter


A mild to severe encephalopathy is most common among patients who have persistent neurologic symptoms following infection with Borrelia burgdorferi (B.b.). Encephalopathy in these patients is characterized by disturbances in memory, attention, verbal fluency, and processing speed, and it is often accompanied by irritability, fatigue, sensory hyperacuities, and sleep disturbance (Fallon et al 2003). The course of illness in many of these cases has been insidious, demonstrating vascular deficits months after initial infectious symptoms.


MRI studies have not demonstrated increased white matter hyperintensities (Aalto et al., 2007), indicating that structural damage is not the explanation for persistent symptoms. Functional imaging studies, however, of patients with later stage neurologic Lyme disease using either Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) scans have consistently demonstrated abnormalities suggestive of impaired blood flow and/or metabolism (Fallon et al., 1997; Logigian et al., 1997). A functional imaging study using brain scans of patients with persistent Lyme encephalopathy used H2 15O to assess blood flow, with and without a hypercapnic challenge, and 2-deoxy-2-(18F)-D-glucose to assess metabolism (Fallon et al., 2010) demonstrated that the deficits primarily reflect abnormalities in cerebral metabolism, although there was evidence for a component of vascular compromise as well. The patients with Lyme encephalopathy had a diminished ability to increase cerebral blood flow in response to a hypercapnic challenge that would suggest vascular compromise (as perhaps from inflammation) as part of the disease process.


With respect to location, Lyme patients demonstrate significant blood flow reductions related to white matter, particularly in the posterior temporal and parietal lobes bilaterally (Fallon et al 2003). A similar impression was reached in the Logigian et al (1997) in which they observed hypoperfusion of the subcortical basal ganglia and white matter was a common feature in Lyme encephalopathy. Hammond (2014) also implicated temporal lobe involvement in chronic fatigue syndrome due to regional cerebral perfusion issues and vascular anomalies. White-matter lesions under a high vascular load are associated with a higher parietal alpha source power (Babiloni et al 2008). White matter architecture is, in general, strongly associated with alpha rhythm (Valdés-Hernández et al 2010).


The role of Inflammation


B.b. spirochetes are usually present in very low numbers in the CNS, and thus infection by itself does not likely cause much direct dysfunction or damage. However, B.b. may cause disease indirectly via the induction of inflammatory mediators, such as cytokines and chemokines (Fallon et al 2010). Cytokines are known to induce prominent systemic and CNS behavioral effects, collectively shaping the subjective, behavioral and physiological components of the sickness response and influencing a range of monaminergic and peptidergic neurotransmitter changes (Anisman et al., 2008).


Cerebral vasculitis caused by B.b. shows an involvement of small vessels, mainly in vertebrobasilar arteries supplying the thalamus (Wilke et al 2000). A direct inflammatory response to invasion by B.b. seems to be the primary pathogenic mechanism of vasculitis in Lyme disease (Schmeidel et al 2004). CNS involvement from vascular or perivascular inflammation is understandable given that adherence of the spirochete to the endothelium lining of blood vessel walls leads to the release of inflammatory mediators which in turn recruit leukocytes to the perivascular tissue; damage to the blood–brain barrier may then ensue with penetration of B.b. into the CNS (Garcia-Monco et al., 1990; Sellati et al., 1995, Huang and Jong 2001).


Given that B.b.  has been found to preferentially injure oligodendrocytes when rat brain has been cultured in vitro, one hypothesis in the literature is that white matter hypoperfusion might reflect injury to the oligodendrocyte resulting in a secondary deafferentation of the cortical structures (Fallon et al 2003).


In summary, the mechanism by which blood flow and metabolic issues arise is proposed to be damage to the vasculature from inflammation. Additionally, changes in neurotransmitter levels result from the response to the cytokines released during the inflammatory state, and a resulting deafferentation between cortical regions is hypothesized.


Relation to Psychological Symptoms


Over 60-70% of those who suffer from chronic Lyme have a psychiatric comorbidity at some time during their illness (Fallon et al 1997, Hassett et al 2009). There is a correlation between history of past traumatic psychological events and chronicity of physical symptoms whether or not the patient had presumed Lyme disease or had received antibiotic treatment. Traumatic psychological experiences predating onset of Lyme disease symptoms may play an important etiologic role in the chronicity of these symptoms. It is possible that prior traumas suppress the immune system in a manner that makes resistance to an invading organism problematic in spite of treatment with antibiotics. It is also possible that patients with chronic psychological problems attend less appropriately to physical cues and thus report to medical facilities later. This behavior would leave a longer period for invasion of the spirochete (Solomon et al 1998).


In most cases, adjunctive antidepressant treatment, for example, will result in greater mood stability, less despair, and consequently a greater ability to participate actively in the process of recovery (Fallon et al 1997). Based on the symptoms recently presented by the client, we believe that treatment for trauma would be the best course of adjunctive support.



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