Hope for Hypothalamic Hamartomas

Our Mission
Hope for Hypothalamic Hamartomas (HopeForHH.org) provides information, support and community to HH patients, caregivers and healthcare providers. We promote research into early detection, improved treatments, living with HH as a complex medical syndrome, and a cure.

Our Goal
Our goal is to create a single, credible source for information about the diagnosis, treatment, and support of individuals with HH. Every family touched by this rare disorder has a unique and often heart-breaking story of how they attained a correct diagnosis. Obtaining a correct diagnosis can take months and even years and often involves incorrect diagnoses. Once a diagnosis is confirmed, many families struggle with choosing an appropriate course of treatment, if one is even available. Regardless of treatment, managing the daily lives of HH patients and dealing with the long term and frequently devastating effects of HH requires ongoing information and support.

Overview of Hypothalamic Hamartoma (HH) Syndrome
Hypothalamic hamartomas (HH) are lesions that arise in the ventral hypothalamic region while the brain is forming in utero. The HH syndrome is commonly associated with a spectrum of clinical, endocrinologic, and psychosocial comorbidities, including refractory epilepsy, precocious puberty, and rage behaviors. Additionally, HH syndrome may include the evolution of an epileptic encephalopathy with developmental regression, psychiatric and behavioral comorbidities. Neuropsychological, sleep and endocrine disorders are also common.

Incidence and prevalence
The prevalence of epilepsy in HH is estimated to be 1 in 200,000 individuals, with a slightly higher number of males versus females. This estimate, which may be low since HH is hard to detect, suggests that there are about 30,000 in the world living with HH. There are likely to be people with epilepsy in whom the syndrome remains undiagnosed or misdiagnosed.

Etiology
Etiology of a hypothalamic hamartoma is not yet fully understood, but it is suspected that genetic factors contribute.

Diagnosis of HH
Diagnostic evaluation of HH remains challenging due to the depth of the lesion, which often results in a scalp EEG reading normal without any evidence of interictal abnormality.

Even a regular surface EEG during a well-known seizure type can be difficult to localize, or may be misleading, because by the time the seizure activity leaves the HH and makes its way to the brain surface, the EEG cannot “see” where it came from initially. The hamartoma can also be difficult to identify on imaging due to its small size and location. This is so even with experienced neuroradiologists, who may be more accustomed to searching for anatomical lesions in the cortex, the more typical location of seizure onset, rather than subcortical regions. For more information regarding diagnosis click here.

Presentation of Seizure Types
Gelastic seizures are almost always the first seizure manifestation of HH.
Most individuals do not feel happy when experiencing a laughing seizure and in fact, may feel anxiety and panic when they are forced to laugh at inappropriate times. Other common features of a gelastic seizure are:

• The person may look startled or even have a look of panic or fear.
• There can also be an unpleasant feeling in the stomach (like butterflies), a tickling in the chest or headache. Lip smacking or frequent swallowing may be seen.
• The eyes may seem vacant and move up and to one side.
• There often is a slight smile that seems a bit forced and laughter or grunting that seems unusual or not appropriate at that time.
• May be triggered by loud noises or sudden actions.
• Often occur as the individual is falling off to sleep.
• These seizures can occur many times a day. In some cases, over 100 a day.

The seizure may present asymmetrically, with the stronger grimacing appearing on the side of the face contralateral to the HH attachment within the third ventricle. Sometimes crying (dacrystic) seizures may be seen. For additional information regarding gelastic seizures click here.

Comorbidities
HH syndrome is associated with a varying comorbidity profile that includes neurodevelopmental, behavioral, endocrine and psychiatric dysfunction.
Precocious puberty presents in around a third of cases – and is often the clue that affects a timely diagnosis. Psychiatric comorbidities exist in over 50% of individuals. Rage attacks, as well as less severe aggressive behaviors and attention problems, are common. Cognitive impairments are also common, and these appear to be progressive in half of cases. In view of the apparent relationship between the epilepsy onset and neurocognitive difficulty, the syndrome is considered an epileptic encephalopathy, with increased seizure burden contributing to worse cognitive outcomes.

Treatment
Anti-seizure medications (ASM), although necessary to reduce the risks of prolonged seizures, are usually not efficacious and overtreatment should be avoided.

Currently, there are several surgical options for HH; disconnection or ablation is the surgical aim. Which surgical approach to use is based upon location, size, and attachment of the hamartoma. Approaches include Gamma Knife radiosurgery, stereotactic radiofrequency thermocoagulation, MRI-guided laser therapy, endoscopic resection and transcallosal resection. MRI-guided focused ultrasound thermoablation is currently in clinical trials for HH. Appropriate surgical intervention can achieve total or partial seizure control but may not reverse encephalopathy. For additional information on treatments click here.