Cognitive and Biomarker Signatures of Late-Onset Temporal Lobe Epilepsy: Toward Non-Alzheimer Neurodegenerative Mechanisms.

Mild traumatic brain injury (mTBI) is defined by the World Health Organization Collaborating Centre Task Force as a neuro-behavioural syndrome produced by external mechanical forces transmitted to the brain in the absence of a penetrating injury []. Although mTBI and concussion are often used interchangeably, as they are in the present review, the terms are not perfect parallels of each other. Concussion is the clinical presentation most often associated with sports while mTBI refers to the wider biomechanical damage cascades in the brain, as defined above. ‘Post concussion syndrome’ (PCS) refers to the set of persistent symptoms an individual experiences beyond a certain recovery timeline, rather than a distinct injury type []. To ensure consistency, the term mTBI is held throughout the review, except where research has specifically cited concussion or post-concussion syndrome. mBI is one of the most frequent neurological events: at least six per thousand people are affected each year, an estimated fifty million cases occur globally per annum, and roughly half the world's population is projected to sustain some form of head injury in their lifetime [, ]. mTBI accounts for approximately 90% of all head trauma presentations, with falls, road-traffic collisions and sport- and work-related impacts the leading mechanisms []. Although the label “mild” implies benignity, a substantial minority of patients develop persistent post-concussive symptoms, and emerging evidence links repetitive and even sub-concussive impacts to chronic neurocognitive impairment, chronic traumatic encephalopathy and elevated psychiatric and suicide risk [, ]. The central clinical problem is that mTBI has no universally accepted diagnostic criterion and no rapidly available objective biomarker to confirm injury or signal recovery [, ]. Diagnosis rests on clinical history and symptom assessment, and up to half of patients sustaining an mTBI may receive an inaccurate diagnosis in the emergency department because memory lapses, stress reactions and secondary injury confound assessment [, ]. Computed tomography and conventional magnetic resonance imaging are typically normal, and the symptom scales in routine use are limited by reliance on self-report and on clinician experience, missing subtle deficits and underdetecting injury in athletes and others motivated to return to play, work or duty [, ]. The consequences of undetected injury—premature return to risk before physiological recovery is complete, and exposure to repeat injury during a window of heightened cerebral vulnerability—make the search for an objective, accessible marker a priority [].