Emerging Symptomatic Treatment of Chronic Traumatic Encephalopathy (CTE): a narrative review

ABSTRACT

Introduction

Chronic traumatic encephalopathy (CTE) is an emergent neurodegenerative tauopathy well characterized pathologically but with limited consensus about clinical criteria. The clinical features include cognitive, behavioral, and motor symptoms such as parkinsonism, gait, balance disorder, and bulbar impairment. Their recognition derives from retrospective studies in pathologically confirmed CTE patients. This is one of the main reasons for the lack of specific pharmacological studies targeting symptoms or pathologic pathways of this disease.

Areas covered

In this narrative review, we overview the possible symptomatic treatment options for CTE, based on pathological similarities with other neurodegenerative diseases that may share common pathological pathways with CTE. The PubMed database was screened for articles addressing the symptomatic treatment of CTE and Traumatic Encephalopathy Syndrome (TES). Additional references were retrieved by reference cross-check and retained if pertinent to the subject. The clinicaltrials.gov database was screened for ongoing trials on the treatment of CTE.

Expert opinion

The similarities with the other tauopathies allow us, in the absence of disease-specific evidence, to translate some knowledge from these neurodegenerative disorders to CTE’s symptomatic treatment, but any conclusion should be drawn cautiously and a patient-tailored strategy should be always preferred balancing the risks and benefits of each treatment.

KEYWORDS:

• chronic traumatic encephalopathy
• dementia pugilistica
• traumatic encephalopathy syndrome
• tauopathies
• biomarkers

Article highlights

• Chronic Traumatic Encephalopathy is a neurodegenerative tauopathy, mostly associated with repetitive mild brain trauma, even if non-traumatic cases have been described in pathological series.

• The core clinical features comprise cognitive, behavioural/mood and motor symptoms but diagnosing CTE during lifetime is often difficult because of overlapping comorbidities.

• In the absence of effective disease modifying strategies, the most distressful clinical features could be symptomatically managed to improve patients’ quality of life, based on tailored strategies.

• Acetylcholinesterase inhibitors and memantine represent standard the treatment of cognitive issues in other dementias; in the lack of specific evidence their usefulness in CTE must be balanced with potential side effects.

• SSRI and other antidepressants and, if needed, mood stabilizing drugs could be useful to manage mood symptoms; in case of psychosis or behavioral symptoms, antipsychotics could be considered.

• Dopaminergic drugs could be useful to manage parkinsonian symptoms, but its effectiveness should be balanced with potential side effects such as psychosis or behavioral symptoms.

• Further pre-clinical and clinical studies are needed to establish evidence-based recommendations for the symptomatic treatment of CTE.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.