Tuberous sclerosis complex is an autosomal dominant multisystem disease.
It usually presents with seizures, mental retardation, and autism.
Tuberous sclerosis complex affects the brain, eye, skin, kidneys,
and heart. It is estimated to affect 1 in 6000 to 10,000 newborns.
The diagnosis of tuberous sclerosis complex is still based on clinical
criteria. To make the definite diagnosis of tuberous sclerosis complex an
individual must have 2 major features or 1 major feature plus 2
minor features. (See Tables 578-2 and 578-3 for major and minor features.) The
non-neurologic clinical manifestations, molecular aspects and management
of tuberous sclerosis complex patients is discussed in Chapter 182.
The hallmark of tuberous sclerosis complex is the involvement
of the brain. This occurs in 95% of affected individuals.
The findings in the brain usually take the form of (1) cortical
tubers, (2) subependymal nodules, and (3) subependymal giant cell
astrocytomas. It is from the cortical tubers that the origin of
the name tuberous sclerosis comes. Tubers are made
up of a collection of abnormally large neurons and glia. Tubers
are most commonly found in the cerebral cortex. The number, size,
and location of the tubers vary tremendously among patients with tuberous
sclerosis complex. Brain MRI is the best way of identifying cortical
tubers. Based on fetal MRI studies, we know that cortical tubers
are formed while in utero in the second trimester.3 Subependymal
nodules are lesions found along the wall of the lateral ventricles
in the brain. In the past they were referred to as “candle
guttering” to convey that their appearance is similar to
drippings of wax from a candle. These lesions do not cause any problems; however,
in 5% to 10% of cases, these benign lesions can
grow into subependymal giant cell astrocytomas. Subependymal giant
cell astrocytomas can grow and block the circulation of cerebrospinal fluid
around the brain and cause hydrocephalus. Median age of ventricular obstruction
due to subependymal giant cell astrocytomas is 9 years. Hydrocephalus
requires immediate neurosurgical intervention.
Epilepsy is by far the most common medical condition in tuberous
sclerosis complex, occurring in 80% to 90% of
patients. In about one third of patients, epilepsy starts out as
infantile spasms. Infantile spasms are characterized by brief, but
often repetitive, muscle contractions, usually involving the head, trunk,
and extremities. The spasms often occur in clusters, and there is
usually crying associated with these spells. Often, the children may
look like they have colic or abdominal discomfort. The EEG often
shows “hypsarrhythmia” (high-voltage, that is, 300–400 mV,
chaotic disorganized background with multifocal spikes, and slow
waves). However, it is important to remember that one can have hypsarrhythmia
without infantile spasms and infantile spasms without hypsarrhythmia,
especially in tuberous sclerosis complex patients.
Patients with tuberous sclerosis complex can develop partial
or generalized seizures. Depending on the seizure type, there are
multiple antiepileptic medications available. If the seizures are
intractable despite the use of antiepileptic medications, epilepsy
surgery can be an option. Individuals with tuberous sclerosis complex
have an increased risk of having neurodevelopmental and behavioral impairment.
Although approximately 50% of people with tuberous sclerosis
complex have normal intelligence, developmental delay and learning
disabilities are commonly found in children with tuberous sclerosis
complex. Therefore, early intervention with physical, occupational,
and speech therapy is highly recommended.
Some of the behavioral disorders that are common in tuberous
sclerosis complex include attention deficit hyperactivity disorder (40–60%),
autism spectrum disorder (20–58%), oppositional
defiant disorder (25%), and sleep disturbance. Autism is
a developmental disability that presents with repetitive behaviors
and difficulty with communication and social interactions. The relationship between
autism and tuberous sclerosis complex has been an intense area of
investigation; however, the underlying cause of autism in patients
with tuberous sclerosis complex remains unclear. Autism is associated
with temporal lobe epileptiform discharges, seizure onset within
the first 3 years of life, and history of infantile spasms.4 An
American Academy of Neurology practice5 recommends searching
for cutaneous abnormalities associated with tuberous sclerosis complex
as a part of the diagnostic evaluation for autism.