Question:
My question is about Neuropsychological issues. My daughter’s began quite suddenly when she was 18 ½ years old. After searching and testing and trials of antidepressant meds, she was started on an acute immunotherapy around age 19 with a high dose of IV corticosteroids, then a few months later with IVIG at CHOP. Then treated monthly there with a combination therapy of steroids/IVIG. There was clear objective and subjective evidence of improvement with these conventional therapies. Therapy was discontinued within that year, not tapered down, MD had passed away at CHOP and she was improving so we ended the therapy without follow-up. Then at age 25, in 2020, slightly before COVID became an isolation problem for the US, and then after, ( so no programs are currently available to her) and she began regressing almost to the same point as when she suddenly was unable to function at age 18 ½. So we took her to a Neurology Center near us and she has been receiving the IVIG monthly. The MD treating her has seen all of our previous notes and he decided we should try the IVIG, so my questions are concerning IVIG dosing and tapering and if this therapy should remain ongoing due to the AE symptoms she has been experiencing? Have you heard of any long-term management of therapy for AE symptoms? Thank you.
Answer:
Regression or loss of skills in adolescents and young adults with Down syndrome is a problem that is being recognized, discussed, and studied more in the last few decades. It was first described in the medical literature in 1946 by Rollin and called “catatonic psychoses.” Since then, it has been described in several papers and given a variety of names. There is no standardly accepted name for the decline although several have been used. There are also a number of proposed causes.
Cardinale et al. (2019) described a small series of individuals with Down syndrome with cognitive decline and additional symptoms. They used the term Down Syndrome Disintegrative Disorder (DSDD) and assessed and treated the individuals for autoimmune encephalitis (AE). They described the use of Intravenous Immunoglobulin (IVIG) to treat these individuals. As the name indicates, IVIG is immunoglobulins (antibodies) given via an IV. They did describe a few individuals who received ongoing treatment for DSDD. At the time of publication, one patient was receiving ongoing IVIG at intervals and one patient was being treated with ongoing rituximab (Rituxan; a monoclonal antibody used to treat immune-related conditions). The other two individuals described in the study do not appear to have been given and/or required ongoing treatment.
Unfortunately, there appear to be little data to answer the question posed above regarding dosing, tapering, and length of course of treatment. As noted, in the Cardinale study, one individual was given ongoing IVIG treatment, and the rest were not. No other studies were found describing the course of IVIG treatment in Down syndrome in those with DSDD.
A few other thoughts on decline in skills seen in adolescents and adults with Down syndrome:
- This is believed to be separate from Alzheimer’s disease. This regression occurs at a younger age. Symptomatic Alzheimer’s disease in people with Down syndrome is thought to be uncommon before age 40.
- Down Syndrome Disintegrative Disorder (DSDD) is one name given to the decline. There is not an official, recognized name. Descriptively, it would seem to be a good choice for a name. However, it is a name I do not favor at this time because it seems to link the condition to autism. It is not clear at this time that there is a link to autism despite some similar symptoms. The later age of onset does not meet the specific criteria for autism. More study is needed.
- I prefer Regression Syndrome (or Adult Regression Syndrome in an adult). It is descriptive but not a diagnosis. It is purposefully a generic term that can be used in a descriptive manner while more study is done and our understanding of the cause and presentation of the cognitive impairment improves (and a formalized, accepted name can be agreed upon).
- In our practice, we have had patients develop this cognitive regression who do not have pre-existing autism. We have also seen a smaller number who did have pre-existing autism. As would be expected by the frequency of autism in Down syndrome, we see more individuals with Down syndrome in our practice who do not have autism than those who do. Therefore, it is expected that more individuals in our practice who are regressing do not have pre-existing autism. In addition, it is more difficult to recognize the decline in some individuals with pre-existing autism and, therefore, DSDD/Regression may not always be diagnosed for those individuals.
- It is not known if DSDD/Regression is a unique entity without a cause from a known condition. In other words, is it possible to find that all of these cases have a diagnosable cause? Or is this a unique entity in people with Down syndrome that does not have another diagnosis? Is it possible that people with Down syndrome are susceptible to regression or loss of skills with similar presentations but a variety of causes? Ultimately, will most (or perhaps all) of these individuals be diagnosed with regression due to a known cause rather than this being a truly unique entity? For example, will diagnoses such as cognitive changes due to an autoimmune encephalitis, catatonia, depression, psychological response to stress, etc. explain all the cases? Those questions are not yet answered. More study is needed.
The Down Syndrome Medical Interest Group-USA has a work group that is regularly reviewing and discussing regression. A number of people who provide physical and/or mental health services for people with Down syndrome are evaluating individuals with regression and sharing information to improve the understanding of the condition. Several articles have been published on the topic. The understanding of possible etiologies and treatments has increased significantly in recent years. In addition, families of people with Down syndrome have developed online groups to support each other.
Here are some additional resources on regression and decline in skills:
References
- Rollin HR. Personality in mongolism with special reference to the incidence of catatonic psychosis. Am J Ment Defic. 1946;51(2):219-237.
- Cardinale KM, Bocharnikov A, Hart SJ, et al. Immunotherapy in selected patients with Down syndrome disintegrative disorder. Dev Med Child Neurol. 2019;61(7):847-851. doi:10.1111/dmcn.14127