Autism is presently recognized as a neurodevelopmental disorder. This means that sometime during gestation brain development is disturbed. Fingerprints indicative of migrational abnormalities and cortical malformations support the premise that autism is a neurodevelopmental disorder. This perspective argues that variability within the genetic makeup of the individual, exogenous/environmental factors, and timing during brain development all account for the heterogeneity of clinical symptoms observed in patients (the so-called Triple Hit Hypothesis, see http://bit.ly/19yLAzL ). Given the neurodevelopmental nature of the disorder it is unsurprising that onset of symptoms is usually observed early during postnatal development. In effect, the older criteria included in the Diagnostic and Statistical Manual (DSM IV-TR) stated that in order to obtain the diagnosis of Autistic Disorder the individual would have to manifest considerable and characteristic impairments in social interaction, communication and range of interests and behavior before 3 years of age. This age of onset criteria has now been removed from the DSM5.
With the introduction of the DSM5 childhood disintegrative disorder or late onset autism was supposed to be subsumed into the larger autism spectrum disorder category. According to writings from the working committee for the DSM5, “We believe that children meeting the DSM-IV-TR criterion for childhood disintegrative disorder will now fit well within the new diagnostic criteria for autism spectrum disorders” (see http://bit.ly/1M5K3TB ). However, other statements within the DSM5 make this a dubious conception. Although the age of onset criteria has been removed, the DSM5 still claims that, “Symptoms must be present in the early developmental period (but may not become fully manifest until social demands exceed limited capacities, or may be masked by learned strategies in later life)”. Adults may thus be diagnosed with Autism Spectrum Disorders but their symptoms are presumed to have developed gradually. In these cases the DSM5 suggests that symptoms may have been subtle but always present.
Unfortunately modern criteria do nothing to clarify the ongoing debate as to the status of regressive, disintegrative, acquired or late onset autism (all the aforementioned terms are synonyms). These are individuals who develop normally but then start to lose speech and social skills between the ages of 15 and 30 months of age. Studies, including some that have been video substantiated, point to a number of cases that qualify as regressive autism. Is this a valid diagnosis? Is it the same as the disorder described by Kanner? Some autistics who may have “developed a vocabulary” could have been parroting sounds (also called echolalia). This has given rise to still another debate as to whether social and language regression should be treated equally when considering a diagnosis of late onset or regressive autism.
In this blog we are not going to discuss the nature of regressive autism but rather expand on a subject that has been readily accepted by most clinicians: the case of adolescents or adults who were unquestionably normal and then developed symptoms diagnostic of autism. These are cases where an inciting cause was known and would thus be labelled as non-idiopathic autism. The underlying causes in these cases are multiple and include mitochondrial disorders, anti NMDA receptor encephalitis, herpes infection, etc. These disorders have in common that they affect large areas of the brain and, by damaging the cerebral cortex, promote seizures.
In this blog we will talk primarily about herpes simplex encephalitis as a cause of late onset autism. Encephalitis denotes inflammation of the brain. Symptoms associated with brain inflammation include fever, a change in the state of consciousness (drowsiness, stupor or coma), alterations in personality, flu-like symptoms, unsteady gait, headaches, confusion and seizures. Common causes of encephalitis include viruses, bacteria, chemicals, and autoimmune reactions.
The most common virus to come to a Neurologist attention because of encephalitis is herpes simplex. This is the same virus that causes common cold sores. Fifty seven percent of American adults are infected with this virus as it lies dormant within one of our cranial nerves. The encephalitis is caused by the retrograde transmission of a reactivated herpes simplex virus along a nerve axon (most probably the olfactory pathway or trigeminal ganglia) and into the covering of the brain. 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 localization within the frontal and temporal lobes helps explain why the patients often display bizarre behaviors, personality changes, anosmia and gustatory hallucinations.
DeLong and colleagues (1981) described 3 children (age range of 5 to 11) who developed an acute encephalitic disorder accompanied by autistic features that resolved after clinical recovery. In 2 of the patients the inciting agent was never identified. However, the third patient had high serum titers for herpes simplex and a computerized tomography (CT) that revealed extensive lesions of the temporal lobe, primarily the left side. Ghaziuddin and colleagues (1992) reported two cases that developed herpes infection in either the intrauterine or early postnatal period and presented features of autism at approximately 2 years of age. In contrast to the previous cases where imaging suggested a predominant involvement of the temporal lobes, Ghaziuddin and colleagues (2002) reported the case of an 11-year-old child who developed symptoms of autism following herpes encephalitis involving the frontal lobes. Another case report came from Gillberg (1986) who described a 14-year old girl who developed a “typical” autistic syndrome as a result of herpes simplex encephalitis. The autistic symptoms persisted long after the acute symptoms of the encephalitis abated. Greer and colleagues (1989) reported a 14-year old boy who was normal till the second grade when he was hospitalized with herpes encephalitis. He later developed significant and persistent social, language and memory deficits. This and other cases where autism developed after an infection at an older age indicate that, at least in syndromic cases, autism is not necessarily a neurodevelopmental disorder (Gillberg 1991).
Delong GR, bean SC, Brown FR III. Acquired reversible autistic syndrome in acute encephalopathic illness in children. Archives of Neurology 38:191-194, 1981.
Ghaziuddin M, Tsai LY, Eilers L, Ghaziuddin N. Brief report: autism and herpes simplex encephalitis. J Aut Dev Dis 22(1):107-113, 1992.
Ghaziuddin M, Al-Khouri I, Ghaziuddin N. Autistic sympttoms following herpes encephalitis. Eur Child Adolesc Psy 11(3):142-6, 2002.
Gillberg C. Brief report: onset at age 14 of a typical autistic syndrome. A case report of a girl with herpes simplex encephalitis. J Aut Dev Dis 16:369-375, 1986.
Gillberg C. Autistic syndrome with onset at age 31 years: herpes encephalitis as a possible model for childhood autism. Dev Med Child Neurol 33(10):92-4, 1991.
Greer MK, Lyons-Crews M, Mauldin LB, Brown FR III (a989) A case study of the cognitive and behavioral deficits of temporal lobe damage in herpes simplex encephalitis. J Aut Dis Dev Dis 11:317-330, 1981.