Following ADHD long-term: "a persistence rate of 27.8%"

Studies such as the one published by Michel Lecendreux and colleagues [1] always catch my attention. Research that follows a group of people over a period of years makes for interesting reading; not least because one gets a flavour for what *could* happen when such findings are applied to a larger population.

The Lecendreux findings focused on a few important issues pertinent to a diagnosis of attention-deficit hyperactivity disorder (ADHD) specifically related to (a) the persistence of ADHD, and (b) the idea that signs and symptoms of ADHD not meeting the thresholds for a diagnosis of ADHD might be rather important. Indeed, that they may merit "a subthreshold diagnostic category" of their own.

So, based on a starting participant sample of just over a thousand families including a child in the "6-12 years age range", interviews were conducted covering various aspects of ADHD and beyond: "symptoms of ADHD, conduct disorder, and oppositional defiant disorder as well as family living situation, school performance, sleep disturbance, eating habits, use of supplemental iron, and history of ADHD treatment." Approaching half of the original sample (492 / 1012) were followed up some 9 years later where "the persistence of ADHD and its impairments and the emergence of new conditions were assessed."

Results: "At follow-up, 16.7% of the children diagnosed with ADHD at baseline met full criteria for ADHD and 11.1% met criteria for subthreshold ADHD, yielding a persistence rate of 27.8%." Diagnosis of ADHD was, by the way, based on DSM-5 criteria (see here). That figure of 27.8% in terms of ADHD persistence from childhood to early adulthood is potentially an important one. It tells us that for a majority of children diagnosed with ADHD in childhood, their symptoms of inattention, hyperactivity and impulsivity will reduce to such a degree that they are no longer considered clinically significant or at least not reaching thresholds for a diagnosis of ADHD. Whether such a reduction in symptoms is through processes such as maturation or the timely implementation of intervention/management strategies needs quite a bit more work. Whether also ADHD potentially 'morphs' into something else as people age also needs further exploration (see here).

Another important detail was also mentioned by Lecendreux et al: "Among children not diagnosed with ADHD at baseline, 1.1% met criteria for ADHD at follow-up." Such a figure is important in relation to the concept of adult-onset ADHD [2] and the question of whether ADHD is a diagnosis with foundations always rooted in infancy. The Lecendreux findings suggest that for some people, this might not be the case and opens the door to possible talk about acquired ADHD for examples. This also sounds very familiar (see here).

Insofar as the issue of a possible 'subthreshold diagnostic category' for ADHD, I find myself agreeing with the "dimensional conceptualization" mentioned by the authors. Several other conditions / states / diagnoses have recognised 'lite versions' of the label. In autism for example, one might see this as social communication disorder (SCD) or mention of the broader autism phenotype (BAP). I'm even minded to place the label known as pathological demand avoidance (PDA) in a similar bracket given recent opinions (see here). Such chatter about 'lite' does not and should not downplay the effects of such sub-threshold labels. It merely acknowledges that there may be a wider spectrum of issues / difficulties experienced outside of the receipt of a core diagnosis.

So it should perhaps be the same with ADHD too, given what is beginning to emerge on the long-term 'effects' that a diagnosis of ADHD and subthreshold ADHD might bring (see here and see here).

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[1] Lecendreux M. et al. A 9-Year Follow-Up of Attention-Deficit/Hyperactivity Disorder in a Population Sample. J Clin Psychiatry. 2019 May 7;80(3). pii: 18m12642.

[2] Cooper M. et al. Investigating late-onset ADHD: a population cohort investigation. J Child Psychol Psychiatry. 2018 Oct;59(10):1105-1113.

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NMDAR encephalitis presenting with "behavioral changes and some autistic features"

Anti N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is yet again (see here) the blogging topic today, as I bring the case report published by Yasmin Khundakji and colleagues [1] to your attention. It's an important case report because, in keeping with the primary focus of this blog, the words 'autistic features' also appear in the Khundakji account. This follows quite a bit of other independent research where autism or autistic features has been mentioned in the context of NMDA receptor encephalitis (see here and see here).

The details? "The patient was a healthy girl" ('was' being the operative word). Some time before she was 2 years of age, she experienced some really quite sudden and stark behavioural changes "manifesting as bouts of irritability, aggression, inconsolable crying, and self-mutilatory behavior (self-biting)." A fever brought about various other somatic symptoms, as eye contact was lost and insomnia set in. "In addition, she developed a progressive regression in gross and fine motor skills and an inability to swallow" with seizures following. Things were getting really serious.

Various tests were carried out which in the most part came up within typical reference ranges (including a "brain MRI"). Someone had their suspicions that NMDA receptor encephalitis *might* fit with the presented profile. Lo and behold, following testing a positive result was received albeit "one month later" (samples had to be sent out of country for analysis). Interventions were put in place ("intravenous immunoglobulin (IVIg) and intravenous methylprednisolone... plasma exchange... rituximab") with some being more successful than others. Of particular note: "A dramatic improvement in her social skills and irritability appeared within hours following plasma exchange." Interesting. Things did eventually improve for the young girl at the centre of the Khundakji paper as we are told that: "Apart from mild speech delay, her neurological exam and developmental milestones are normal."

What lessons can be learned from such case reports? How about starting with the idea that rapid onset childhood regression that includes 'autistic features' should always be investigated as a sign of unmet medical need such as a response to infection (see here)? Perhaps also acknowledge that the presentation of autism or autistic features is not a life-long, immutable, set-in-stone scenario for some people (see here and see here and see here)? And as for the effects of plasmapheresis (plasma exchange) on this particular young child linked to a "dramatic improvement in her social skills and irritability", I'm wondering whether there is a research study or two to be designed and conducted on this topic (with due care)?

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[1] Khundakji Y. et al. Anti-NMDA receptor encephalitis in a toddler: A diagnostic challenge. International Journal of Pediatrics and Adolescent Medicine. 2018; 5: 75-77.

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"Has Daniel always been autistic?"

"Has Daniel always been autistic?"

That was the question that led to Twitter uproar and newspaper headlines calling a TV presenter an 'idiot' and "embarrassing" and "ignorant" these past few days. Some have even called for veteran daytime TV presenter Richard Madeley to be sacked, as one of the premier national autism charities here in Blighty authoritatively announced "autism is a lifelong condition, people are born autistic, it’s not something a child grows out of" following the reporting of an interview between Madeley and Daniel Wakeford, one of the stars of the not particularly well titled TV series called The Undateables. Personally, I would have liked to have seen said charity comment on how the term 'undateable' really shouldn't be used in this day and age with any diagnosis/label in mind...

Emotions ran high following the interview, as many parents of children with autism and autistic people voiced their opinions about their own personal experiences of autism. These are all valid opinions. The problem however, is that within the wide - very wide - heterogeneity that is autism, some of the peer-reviewed science on the topic of autism actually supports the line of questioning from Madeley. Some of the peer-reviewed science highlights the sweeping error in saying that autism is (a) lifelong for everyone and (b) that everyone, past, present and future is 'born autistic'.

OK, first things first, autism is a label ripe for sweeping generalisations. We've seen it numerous times as psychological theories for example, have swept through proclaiming that everyone with autism is lacking a theory of mind or empathy or some other related construct. Likewise, I've seen people quite vehemently opine that autism is the product of this or that 'environmental factor' insinuating that simple changes to drink, food or medicines use for example, will 'stop autism'. The reality however is that autism is a label used to describe vast heterogeneity. It's also a label that says nothing about how a person came to be autistic and nothing about the prognosis of their presentation or their life in general.

So what is the cold, objective peer-reviewed scientific evidence to say that autism is not present from birth for everyone? Well, it's multi-fold. It comes from a number of studies that have followed children from early infancy into later childhood to see whether autism *always* manifest from the very earliest days. Take the recent findings from Sally Ozonoff and colleagues [1] (see here for my take) that concluded among late diagnosed children in their cohort: "Seven showed very little evidence of ASD [autism spectrum disorder] in preschool, whereas 7 demonstrated subtle, subthreshold symptomatology." Add it to other independent data [2] that "validate parents' reports that ASD may appear after a period of nonautistic development" (also that "such reports should not be attributed to recall bias") and then throw in the idea that 'regression', as in a regression of previously acquired skills, is perhaps no stranger to many instances of autism (see here). Then to top it all add in other data highlighting specific cases of 'acquired autism' following exposure to particular post-natal infections for example (see here), and the old 'autistic from birth' mantra does not universally hold for everyone diagnosed as being on the autism spectrum. The evidence against the sweeping 'autism is a lifelong condition' statement made following the interview? I'll direct you to some of the numerous occasions that I've talked about such an idea on this blog (see here and see here and see here) based again on the available peer-reviewed science. Cold. Objective. Science.

Minus making any sweeping generalisations of my own, there is scientific evidence out there that 'born autistic' is not something that can be universally applied to everyone on the autism spectrum no matter how many people would like it to be so. In that respect, the question from Richard Madeley was not ignorant nor disrespectful but rather quite sensible and easily discernible from the available science. The fact also that Daniel's mother Carol talked about a 'loss of his language abilities' in her reply to the question (something I'm sure must have been mentioned before the interview took place and was aired) kinda adds to the sound reasoning for Madeley to ask. It also implies that science should keep studying such an important phenomenon.

It seems that when Carol Wakeford responded with the words 'yes, well there's controversy about that' as the first part of her answer to Madeley's question about Daniel, she certainly wasn't wrong...

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[1] Ozonoff S. et al. Diagnosis of Autism Spectrum Disorder After Age 5 in Children Evaluated Longitudinally Since Infancy. J Am Acad Child Adolesc Psychiatry. 2018 Nov;57(11):849-857.e2.

[2] Landa RJ. et al. Social and communication development in toddlers with early and later diagnosis of autism spectrum disorders. Arch Gen Psychiatry. 2007 Jul;64(7):853-64.

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