Cognitive problems arising from brain injury are common, frequently persistent, usually disabling and sometimes hidden. They include impairments of attention, memory and executive functioning.
The keystones of treatment comprise cognitive rehabilitation together with adaptive processes and technology.
In some cases cognitive problems improve following treatment with cognition-enhancing drugs.
Treatment response to cognitive enhancing drugs can be very difficult to predict given the multiple ways by which the brain can be damaged and the different levels and places at which damage can occur.
What comes next relates to the investigation and treatment of impaired information processing and motivation following traumatic brain injury (TBI).
We know that ascending nerve cell pathways which rely on the neurotransmitter dopamine for their effectiveness are frequently damaged in TBI and that the resultant hypodopaminergic state is associated with problems in processing information and in maintaining motivation.
We also know that treatment with Methylphenidate, a drug which enhances the action of dopamine and whose effects in ADHD are now well understood, may in some instances improve attention, concentration and executive function after TBI.
We cannot reliably predict who will and who will not respond to Methylphenidate.
This has led to both scepticism on the part of some doctors as to the effectiveness of Methylphenidate as a cognitive enhancer and to a significant number of studies in which its effectiveness has not been confirmed.
But help may be on hand. A well designed study* from Dr Peter Jenkins and his colleagues at Imperial College uses I-ioflupane SPECT scanning to examine dopamine transporter binding in the caudate nucleus and thereby the integrity of dopaminergic systems in patients following brain injury.
They compared 40 patients with moderate to severe brain injury with 20 healthy age and gender-matched controls on a variety of neuropsychological and neuroimaging parameters.
They then carried out a randomised, double-blind, placebo-controlled crossover study of Methylphenidate at a dose of 0.3mg/kg twice a day versus placebo within the patient group.
All of the TBI patients demonstrated reduced information processing speed and increased apathy in comparison to controls.
There was a significant response to Methylphenidate in terms of improved information processing speed and improved apathy in those patients with reduced dopamine transporter binding but not in those with normal binding.
These findings are important for two reasons.
Firstly because they increase our understanding of why Methylphenidate is effective in some patients and not others and secondly because it offers the possibility of a treatment-response predictive test for the future.
In the words of the author “this shows that identifying patients with a hypodopaminergic state after traumatic brain injury can help stratify the choice of cognitive enhancing therapy”.
The study has limits. The treatment period is only of two weeks duration and no provision was made to see if those patients who responded continued to respond over time.
It did not establish a clear protocol for identifying a level of hypodopaminergicity that could be confidently used to decide whether or not to treat at this point in time. Further work is needed.
I-ioflupane SPECT is currently used in the NHS in the diagnosis of Parkinson’s Disease, Parkinson-Plus Syndromes and occasionally in the diagnosis of Lewy Body Dementia.
It is safe and largely free from adverse effects. But it is a relatively costly investigation and it requires a cooperative patient.
Whilst it is unlikely to become a routine investigation in the future, neuropsychiatrists may find themselves requesting it in situations where there is doubt or scepticism as to the potential benefits of treatment with Methylphenidate.
Dr Tim Howard is a consultant neuropsychiatrist for Elysium Neurological, working at the Avalon Centre in Swindon.
*Reference: Stratifying drug treatment of cognitive impairments after traumatic brain injury using neuroimaging. Peter O Jenkins et al (2019)
