Regression in Autism (3):

Late Onset and Late Autistic Regression

In most cases, ASD is diagnosed between 15 and 30 months. Some children exhibit typical early development, only to lose acquired language and social skills between 15 and 30 months. These cases qualify as regressive autism.

However, there are instances of late-onset autism where individuals appear to develop typically until adolescence or even adulthood before displaying symptoms consistent with autism. In such cases, an identifiable neurological insult, such as, e.g., herpes infection or autoimmune encephalitis, is often present.[1]

Herpes simplex encephalitis (HSE)

A known cause of late-onset autism is Herpes Simplex Encephalitis (HSE) – a severe neurological disorder primarily caused by the Herpes Simplex Virus (HSV), specifically HSV-1. The pathophysiology of HSE involves the viral invasion of the central nervous system (CNS), leading to inflammation of the brain, particularly the temporal lobes. The virus typically enters through the olfactory routes or following a peripheral infection, such as a cold sore or genital lesion. Once in the CNS, the HSV triggers an inflammatory response, leading to neuronal apoptosis and significant neurological dysfunction. From the coverings of the brain the virus infects the adjacent temporal and inferior frontal lobes first and then spreads to the rest of the brain. Neuropathological examination reveals a greater degree of brain destruction, inflammation and reactive response than in any other viral encephalitis. The localisation within the frontal and temporal lobes helps explain why the patients often display bizarre behaviours, personality changes, anosmia and gustatory hallucinations (Casanova 2015).

The clinical manifestations of HSE are often nonspecific in the early stages, which complicates timely diagnosis. Initially, individuals may initially experience flu-like symptoms, including fever and headaches, that may progress to seizures, confusion and focal neurological deficits.[2]   

Case reports linking HSE to late onset autism

Several published case studies illustrate this association:

Gillberg (1986) who described a 14-year-old girl who developed a “typical” autistic syndrome as a result of HSE. The CT scan of the head showed widespread bilateral destruction of brain parenchyma and the temporal lobes, with some medial involvement of the lower parts of the parietal lobes. The autistic symptoms persisted long after the acute symptoms of herpes encephalitis, such as fever and alteration of consciousness, subsided.

Greer and colleagues (1989) commented on the cognitive and behavioral deficits of temporal lobe damage in HSE. They described a 14-year-old boy who regressed after HSE. He later developed significant and persistent social, language and memory deficits.   

Another case report came from Ghaziuddin et al. (2002) who reported the case of an 11-year-old child who developed symptoms of autism following HSE involving the frontal lobes.

Jones and Kerwin (1990) described regression in a patient with Asperger syndrome, who showed left temporal lobe damage on computerised tomography.[3]

Gillberg C. (1991) described a previously healthy man who contracted herpes encephalitis at the age of 31 years, and over the following months developed all the symptoms considered diagnostic of autism. This case report casts doubt on the notion of autism as an exclusively developmental disorder. It is suggested that temporal lobe damage may cause autism in some cases.

These cases share a common theme: although the onset age defies typical diagnostic criteria for ASD, the symptom profiles align closely with core autism features. Importantly, temporal lobe damage, particularly when acquired after typical development, may yield different behavioural outcomes than congenital developmental abnormalities.

Despite the evidence pointing to the involvement of temporal lobes in herpes encephalitis, no causative role for the virus in the etiology of the disorder has been established.

Acquired reversible autistic syndrome

DeLong et al. (1981) identified a clinical presentation of acquired autism consistent with infantile autism in three children experiencing acute encephalopathic illness. Notably, this condition was reversible in two of the cases, distinguishing it from similar presentations observed in adolescents and adults after HSE:

One child demonstrated elevated serum herpes simplex titers, and a computerized tomographic (CT) scan revealed significant lesions in the temporal lobes, predominantly on the left side. In contrast, the other two children, who exhibited comparable clinical syndromes, had normal CT scans, and no identifiable etiological agent was determined. These cases serve as compelling examples of acquired and reversible autistic syndrome in childhood, highlighting the potential for recovery in specific clinical contexts.

This is important because symptoms arising from the failure of development of temporal lobes in early life may be different from those arising from late destruction of previously normal lobes. This report adds further support to the hypothesis that herpes simplex encephalitis, possibly through the involvement of temporal lobes, is associated with autism but does not propose a direct cause-and-effect relationship between the two.

The Role of Catatonia in Late Regression in Autism

Catatonia is increasingly recognised as a significant—but often overlooked—cause of late regression in autistic individuals, particularly during adolescence and early adulthood. It is a complex neuropsychiatric syndrome characterised by motor abnormalities, behavioural rigidity, emotional withdrawal, and disturbances in volition and vegetative functions.

Originally conceptualised as a subtype of schizophrenia, catatonia is now understood to occur across a wide range of psychiatric and medical conditions. It represents a kind of “final common pathway” for severe mental health disorders and has been observed in mood disorders, psychotic disorders, obsessive-compulsive disorder, and neurodevelopmental conditions such as Autism Spectrum Disorders (ASDs) (Dell'Osso et al. 2023).

There is a notable overlap between the core features of autism and catatonia, which can make diagnosis challenging. Catatonia affects an estimated 8–11% of individuals with autism—a figure that is likely underreported due to clinical heterogeneity, symptom overlap with autism itself, and a general lack of awareness among healthcare professionals. Alarmingly, catatonia in autism often presents as a form of late autistic regression, typically emerging from puberty to early adulthood (Ruggieri 2023).

Unlike early regression, which tends to occur in early childhood among previously typically developing children, late regression in autism manifests in adolescents with an established diagnosis. Ghaziuddin (2021) studied 20 individuals with ASDs who experienced late regression, with the average age of onset being 13 years. Early signs included obsessive slowing and compulsive rituals, followed by motor abnormalities, aggression, and mood disturbances. Catatonia was the most common comorbid condition, present in 17 of the 20 cases. Despite various treatments, outcomes were frequently suboptimal, highlighting catatonia as a critical contributor to late regression in autism.

Further evidence from Wing and Shah (2000) showed a high prevalence of catatonia-like features in autistic individuals, particularly those aged 15 and older. Severe deterioration was observed in 17% of those assessed. Notably, children with intellectual disabilities or language disorders showed some similar symptoms, but these were significantly less frequent than in autistic individuals. A history of social passivity and expressive language impairment appeared to be associated with the risk of catatonic deterioration.

The impact of autistic catatonia can be profound, with long-lasting negative effects for families, healthcare workers, and high-cost to the healthcare system.. Burns et al. (2021) presented two case studies of excited catatonia[4] in young autistic men. Both patients experienced delayed diagnoses and struggled to access appropriate care. The first patient, high-functioning and employed part-time, experienced a rapid and dramatic behavioural change, leading to diagnosis within three months. The second, low-functioning and nearly non-verbal, endured a slow five-year decline marked by escalating aggression that ultimately required emergency electroconvulsive therapy (ECT). In both cases, symptoms such as agitation, unprovoked aggression, urinary incontinence, compulsive behaviour, and stereotypies were prominent. One patient required ongoing weekly ECT to maintain stability after numerous failed medication trials and hospitalisations.

These cases underscore how under-recognised catatonia remains in autism. Its clinical presentation can mimic or overlap with ASDs, making timely identification difficult. This underlines the importance of raising clinical awareness: when adolescents or young adults with ASDs exhibit sudden or progressive deterioration in functioning, catatonia should be considered as a possible underlying cause.

Conversely, the possibility of an underlying autistic disorder should be considered if an individual presents with catatonia. Possible physical or psychological causes should be investigated and treated if found. In the absence of a treatable cause, there is no known cure for catatonia, but appropriate care and environmental management can help to alleviate the problems for the individual concerned and for their care-givers (Wing & Shah 2000).

Ultimately, autistic catatonia represents a serious, often debilitating condition that imposes a heavy burden on individuals, families, and the healthcare system. Improved awareness, timely diagnosis, and targeted management are essential for mitigating its long-term impact.

It is probable that there is an underreporting of catatonia, especially in autistic people, due to the lack of alertness about it, the clinical heterogeneity and the similarity of many of its symptoms with manifestations of autism. Often it can even express itself as a late autistic regression from puberty to adult life (Ruggieri 2023). 

It is important for clinicians to be aware of the possibility of catatonia when investigating reasons for deterioration in skills and behaviour occurring in adolescents and adults with autistic spectrum disorders. Conversely, the possibility of an underlying autistic disorder should be considered if an individual presents with catatonia. Possible physical or psychological causes should be investigated and treated if found. In the absence of a treatable cause, there is no known cure for catatonia, but appropriate care and environmental management can help to alleviate the problems for the individual concerned and for their care-givers (Wing & Shah 2000).

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Cases of late-onset autism and/or autistic regression, whether triggered by herpes encephalitis or catatonia, highlight the importance of careful differential diagnosis and awareness of neuropsychiatric comorbidities.

While not every case of regression or social withdrawal in adolescence indicates autism, clinicians should consider both organic brain damage (as seen in encephalitis) and psychiatric syndromes (like catatonia) in their evaluations. Early recognition and treatment can dramatically improve quality of life.

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[1] These are generally referred to as syndromic autism, where symptoms of autism emerge secondary to broader neurological damage (Casanova 2015).

[2] HSE is associated with significant morbidity and mortality in adults and children despite antiviral treatment. If left untreated, it can result in a mortality rate of up to 70%, and only a minority of individuals recover fully without residual deficits (Tyler 2004). In adults, even with prompt diagnosis and treatment, the mortality is estimated to be between 20 to 30%, (Whitley et al. 1986; Sköldenberg et al. 1984). Many of those who recover may suffer from permanent neurological and/or psychological deficits, such as amnesia.

[3] This does not imply, however, that temporal lobe pathology is commonly associated with autism. In fact, a variety of lesions in the brain have been documented as associated with autism, in particular – the cerebellum.

[4] Catatonia is sometimes divided into two subsets: retarded catatonia and excited catatonia. The former is characterised by slow movement and unresponsiveness; the latter is typified by restlessness or agitation, and sufferers may have a fast heartbeat and raised blood pressure. Although catatonia is most commonly witnessed in its retarded form, excited catatonia - also known as malignant or lethal catatonia - is associated with serious risks of complication, including altered consciousness, hyperthermia and internal body process dysfunctions (Rasmussen et al 2016).