Persistent symptoms and incomplete recovery are common after mild traumatic brain injury (TBI), commonly known as concussion, despite the 'mild' label. A new study from the University of Cambridge, published in Brain, has suggested that chronic symptoms may be linked with early thalamic pathophysiology.
Investigators said that concussion resulting from a blow or jolt to the head – for example from a fall, sports injury, or accident – is often followed by ongoing symptoms that may include depression, cognitive impairment, headaches, and fatigue.
While clinicians often predict that 90% of concussed patients will have fully recovered after 6 months, emerging evidence suggests that in fact only half achieve a full recovery.
"This means that a significant proportion of patients may not receive adequate post-injury care," researchers said.
No Current Way to Predict Speed of Recovery
Researcher Dr Emmanuel Stamatakis, leader of the cognition and consciousness imaging group in the Department of Clinical Neurosciences at the University of Cambridge, explained: "Worldwide, we're seeing an increase in the number of cases of mild traumatic brain injury, particularly from falls in our ageing population, and rising numbers of road traffic collisions in low- and middle-income countries.
"At present, we have no clear way of working out which of these patients will have a speedy recovery and which will take longer, and the combination of over-optimistic and imprecise prognoses means that some patients risk not receiving adequate care for their symptoms."
Currently, patients with suspected concussion typically receive either a CT scan or an MRI scan to look for structural problems, such as inflammation or bruising – yet, even if these scans show no obvious structural damage, a patient's symptoms may persist.
To investigate the suspected role of the thalamus, the team studied functional MRI scans from 108 patients aged 18-70 with mild TBI, a Glasgow Coma Scale of 13 to 15, normal CT, and no history of previous concussion or neuropsychiatric disease, and compared them with fMRI scans from 76 matched healthy volunteerscontemporaneously imaged on the same MRI systems. The patients were also assessed for ongoing symptoms.
Almost Half of Patients Incompletely Recovered at 6 Months
Of the mild TBI cohort, 47% showed incomplete recovery 6 months post-injury,with their most common symptoms being fatigue, poor concentration and headaches. Counter-intuitively, concussion was associated with increased connectivity between the thalamus and the rest of the brain – and the greater this connectivity, the poorer the prognosis for the patient.
First author Rebecca Woodrow, a PhD student in the Department of Clinical Neurosciences at the University of Cambridge, said: "Despite there being no obvious structural damage to the brain in routine scans, we saw clear evidence that the thalamus – the brain's relay system – was hyperconnected. We might interpret this as the thalamus trying to over-compensate for any anticipated damage, and this appears to be at the root of some of the long-lasting symptoms that patients experience."
The authors said: "Acute fMRI markers differentiated those with chronic post-concussive symptoms, with time- and outcome-dependent relationships in a sub-cohort followed longitudinally. Moreover, emotional and cognitive symptoms were associated with changes in thalamic functional connectivity to known dopaminergic and noradrenergic targets, respectively."
The results could aid identification of patients at risk of chronic symptoms, provide a basis for development of new therapies, and could facilitate precision medicine application of these therapies, they said.
Dr Stamatakis added: "We know that there already drugs that target these brain chemicals, so our findings offer hope that in future, not only might we be able to predict a patient’s prognosis, but we may also be able to offer a treatment targeting their particular symptoms."
Even 'Mild' Knocks can Have Serious and Lasting Effects
Asked to commend by Medscape News UK, Colin Morris, director of communications for brain injury charity Headway, said: "We welcome this study that improves understanding of concussion and its longer-term impacts. It highlights that even so called 'mild' knocks can have serious and lasting effects on individuals and it underlines the seriousness with which we need to treat all brain injury.
"Many people we support report ongoing problems following concussion, with debilitating symptoms such as depression, headaches, fatigue, and memory problems, and we need this kind of research which will lead to better identification and management of post-concussion syndrome."
Funding for the study was provided by the EU's 7th Framework Programme, Medical Research Council Doctoral Training Programme Grant, Gates Cambridge Trust, Academy of Medical Sciences/The Health Foundation Clinician Scientist Fellowship, NIHR Cambridge Biomedical Research Centre, Stephen Erskine Fellowship at Queen's College, Cambridge, the Canadian Institute for Advanced Research, the British Oxygen Professorship of the Royal College of Anaesthetists (DKM), NIHR Senior Investigator Awards, and Medical Research Council UK. DKM reports grant support from the National Institute for Health Research, Medical Research Council, Canadian Institute for Advanced Research, and the European Union. He is in receipt of collaborative research grant funding with Lantmannen AB, GlaxoSmithKline Ltd. and Cortirio Ltd, and personal fees from Calico LLC, GlaxoSmithKline Ltd, Lantmannen AB, and Integra Neurosciences. All other authors report no competing interests.
