Most Common Symptoms

There are two hallmark symptoms of a hypothalamic hamartoma, epilepsy and precocious puberty.

Some people develop one, or both symptoms, depending on the size and location of the tumor.  Specifically, epilepsy develops if the tumor is in the back of the hypothalamus, whereas precocious puberty develops if the tumor is in the front and near the pituitary stalk.  If a tumor is large enough, it may encompass both locations.  Both of these symptoms develop as early as infancy.

Epilepsy

Hypothalamic Hamartomas (HH) with epilepsy is:

  • A rare epilepsy syndrome that runs a wide spectrum of symptoms or comorbidities and changes over time with intensity and frequency of different seizure types and symptoms.
  • Characterized by intractable epilepsy – meaning the seizures often don’t respond well to anti-seizure medications (AEDs).

One of the first seizure types most often experienced by an individual with HH and epilepsy is the gelastic seizure (laughing seizure). These rare seizure types are also the hardest to diagnose. Many individuals experience gelastics as the first seizure type beginning in infancy, yet go years before they are correctly diagnosed. It is often not until other seizure types emerge that the individual or a family member describes this “quirky laugh” that has been around for years!

Gelastic seizures:

  • Often look like a forced smile, sometimes only a one-sided grin. One eye may droop. Laughter or grunting may be very rhythmic and repeat several times.
  • May occur infrequently (weekly, monthly) or they may be frequent (daily, hourly or even just a few minutes apart 24/7).
  • May be brief and last less than 30 seconds, or they may go on for longer periods lasting minutes.
  • Often occur as an individual is dropping off to sleep. They may occur throughout the night, waking the individual. It is not unusual for the individual to drop right back to sleep.
  • They can be disconcerting to the individual and they may feel the need to run. They may feel they are running from something uncomfortable or not even know why they are running.
  • May be unsettling to the individual because, for many, they cannot be completely suppressed – only covered up with a different vocalization or over emphasized laugh.
  • Are not usually painful but may leave a person feeling tired.
  • May be mis-diagnosed as “tics”, “quirky laugh”, acid reflux, autistic behaviors.
  • Some individuals have unpleasant sensations in their stomach prior to or in conjunction with a gelastic seizure and this can lead to a diagnosis of gastrointestinal distress or acid reflux.
  • Can be triggered by loud noises, fearful responses, excitement, anxiety, anger, fatigue, stress, frustration.
  • May not present as a laugh or giggle, but rather an unusual type of breathing for some.
  • Are also often misdiagnosed because they do not register on an EEG because their location is very deep in the brain.
  • The presentation of a laugh during a seizure is often different than the person’s true laughter.

Another common early seizure type is the dacrystic seizure. Dacrystic seizures appear like crying or sobbing but may have no emotion of sadness associated with it. These seizures often occur in conjunction with the gelastic seizure, but don’t always, and can occur alone.

Central Precocious Puberty

Approximately 40% of children with HH develop central precocious puberty.

Precocious puberty is early onset of puberty, typically before the age of 8 in girls and 9 in boys, due to damage to the hypothalamus.  The result is the release of gonadotropin-releasing hormone, which then communicates to the pituitary gland to release the follicle-stimulating hormone (FSH) and luteinizing hormone (LH).  These hormones are responsible for the observable biological markers in puberty.  For example, children may begin to have pubic hair, body odor, acne, grow abnormally fast with height and weight, as well as begin menses and breast growth (girls) and developed genitals and erections (boys).  In infants with hypothalamic hamartomas, these symptoms can begin to develop as early as 1 or 2 years old.

Other Neurobehavioral Comorbidities

For reasons unknown, 50% of individuals with HH and epilepsy have worsening symptoms over time, including cognitive functioning and behavior.  Over 80% of individuals with HH reported psychiatric symptoms and have been additionally diagnosed with the following:

  • Oppositional Defiant Disorder – a continuing pattern of negative/angry/irritable mood with argumentative/defiant behavior to peers and people of authority.
  • Attention Deficit Hyperactivity Disorder – ongoing and persistent difficulty with attention, excessive activity levels, and controlling impulsive behavior that interferes with daily activities.
  • Anxiety – excessive and persistent worry that does not go away and may start to interfere with someone’s ability to complete daily activities
  • Depression – persistent feelings of sadness or loss of interest that does not go away and interferes with daily activities.
  • Conduct Disorder – a child or adolescent’s ongoing pattern of antisocial behavior and aggression towards others with serious violations of rules, which may include breaking the law.
  • Mood Disorder – mood is distorted or inconsistent with the circumstances and interferes with a person’s ability to function.
  • Autism Spectrum Disorders – developmental challenges in the ability to communicate and socialize, while also demonstrating repetitive/restrictive patterns of behavior or interests.
  • Obsessive Compulsive Disorder – repeated and unwanted thoughts and/or the need to engage in certain behavior or perform a certain routine, all of which interferes with daily activities
  • Auto-Aggressive Behavior – self harming behavior.
  • Extreme decline in executive functioning – processing speed and short-term memory

Individuals with seizures due to HH commonly display a wide range of cognitive impairments. Impairments may range from slight to severe. Most prevalent are problems with working memory, long-term retrieval, and processing speed, as well as visual and verbal learning and memory. Other skills include: concentrating, controlling emotions, time management, and multitasking

The exact relationship between cognitive ability and the influence of seizure type, frequency, and onset is not well understood. There have been reported cases of patients with gelastic seizures and HH with normal cognitive functioning, yet these cases are less common. It is unclear at this point if size and attachment of the HH to the hypothalamus have a direct affect on cognitive functioning.

Compared to children, adults showing symptoms later in life appear to have less severe seizures, less severe learning and behavior difficulties, and better occupation and social connections.

Over the course of a patient’s journey, explosive anger can be one of the most challenging symptoms for the individual and the family.  Specifically, children are often described as having behavior aggression with poor frustration tolerance.  Approximately 20% of patients engage in these ‘rage attacks,’ which are further described as sudden, out-of-control bursts of anger that can start without warning or an obvious trigger.

Endocrine Comorbidities

Some individuals also experience endocrine issues including:

  • Temperature dysregulation
  • Hypothalamic obesity
  • Hypothyroidism
  • Lack of or abnormal sweating
  • Inappropriate thirst response
  • Panhypopituitarism
  • Growth hormone deficiencies
  • Testosterone or estrogen deficiencies

Some of these can occur prior to surgical intervention and many more occur as a result of damage to the hypothalamus during surgery.