Understanding the path to a proper diagnosis

Diagnostic tools and Early Detection

The diagnosis of HH is based on an individual’s
1) neurological symptoms and 2) radiographic tests.
Early detection can improve the likelihood of a successful treatment outcome. However, it is worth noting here that many of the tools used for diagnosis in the hands of an inexperienced health professional can lead to misdiagnosis and further delay proper treatment. It is highly recommended that any tests be conducted and/or reviewed by individuals with experience in diagnosing and treating individuals with HH.

Neurological and Physical Symptoms

Neurological symptoms can include worsening seizure volume, length and type, decline in learning skills, increased behavior problems, and/or memory deficits. Two other conditions associated with HH that can ultimately lead to its discovery are precocious puberty and Pallister-Hall Syndrome. Precocious Puberty is the most common endocrine condition leading to diagnosis of HH and is defined as unusually early onset of puberty (before age 8 for girls and age 9 for boys). It has been reported as early as infancy. It can occur by itself, without seizures or other neurological problems.

Pallister-Hall syndrome is a less common genetic disorder that affects the development of many parts of the body. Most people with this condition have extra fingers and/or toes (polydactyly) and the skin between some fingers or toes may be fused (cutaneous syndactyly). Pallister-Hall can result in an HH that is often large, however, epilepsy occurs less frequently and is reported to be relatively mild compared to individuals with HH alone.

Diagnostic Testing

There are many diagnostic tests available today to assist in the process of diagnosing and treating HH. Some tests will be used more often in the initial diagnosis phase and others will be used exclusively in the course of treatment. While some tests will be standard practice at most hospitals (ie MRI and EEG), other hospitals may not have access or chose to use the newer technology when treating HH. We have included the spectrum of diagnostic tests, their definition, and in some cases the challenges associated with that test and HH. Our goal is to familiarize you with the terms and help facilitate a conversation with your provider when it comes to testing.

Magnetic Resonance Imaging (MRI)

MRI uses powerful magnets, radio waves and computers to image inside the body.  Imagine a loaf of bread with one raisin (HH) in the middle. Now take a (virtual) bread knife and slice the bread with the intention of slicing right through a hypothalamic hamartoma, which is sometimes as small as the raisin.  Not an easy task.  During an MRI, usually several types of pictures are taken, in order to see different attributes of the brain tissue.  For each type of picture, which is called an MRI sequence, MRI controls are altered to different preset settings.  The MRI staff and technologists often use the following protocol sequence parameters to get the best pictures of the hypothalamic hamartoma.  

  • 3D T1W SPGR, axial 0.9mm isotropic voxels
  • Sag T1W – min TE; 3mm slice, 0.5mm gap; FOV 20cm
  • Sag T2W(FSE) – 2mm slice no gap; FOV 20cm
  • Cor T2W(FSE) – 2mm slice no gap; FOV 16cm
  • Cor T1W – 3D SPGR; 2mm slice; FOV 24cm – recon for axial
  • Axial T2W(FSE) – routine brain

The exam is performed while laying on a table that slides into a long tube.  A coil (looks like a cage) will be placed over the head.  Ear protection is provided because the MRI will make loud noises during the scanning process.  Movement of any kind can decrease the quality of the imaging.  If the patient is unable to hold still, anesthesia can be used.  Contrast (injectable agent) can be used to help better visualize structures in the brain but the HH will not enhance or highlight with the use of contrast. If an HH is very small, it can be easily missed by an individual not experienced in locating HH lesions.  MRI does not use radiation.

MRI of 15 month old girl with large HH prior to removal (click image for larger view)

MRI-PreOp-2-lrg

MRI of same girl at 3.5 yrs old after HH surgically removed by TC Approach (click for larger view)

MRI-PostOp-2-lrg

Electroencepahalogram (EEG)

EEG is a test that detects electrical activity in the brain using small, metal discs (electrodes) attached to the scalp.  The brain is constantly sending electrical signals even while sleeping.  Because the HH is deep within the brain, far away from the scalp EEG electrodes, the EEG may not detect any abnormal activity during a seizure.  This is especially true for gelastic (laughing) seizures.

Video Electroencepahalogram (VEEG)

Video EEG is the same as an EEG but with a video.  The study is completed over a few days in the hospital to hopefully witness a seizure.  Patients or caregivers could be asked to push a button to indicate when a possible seizure event is happening, or they can be monitored real time by a specialist in the Epilepsy Monitoring Unit (EMU).  Being able to witness the seizure, and correlate it to the EEG, can be useful to determine seizure activity. A video EEG is often more useful in diagnosing HH and gelastic seizures, as subtle facial changes and eye movements can be identified and correlated to EEG activity.

Magnetoencephalography (MEG)

MEG (magnetoencephalography) uses a machine to record magnetic fields from the brain.  This may show more information than a conventional EEG.  It is performed to map brain function and to identify the exact location of the source of epileptic seizures. The exam can also be correlated with an MRI. Unfortunately, preliminary evidence suggests that although MEG has less spatial limitations than surface EEG, it is still not able to localize seizures from HH. 

Computerized Tomography (CT)

CT uses radiation to image the brain.  It takes (virtual) slices like an MRI.  CT is often used in emergency visits for a fast look at the brain to rule out multiple brain issues.  Radiation for a head CT is relatively low. It is not generally usually used as a diagnostic tool for HH in a non-emergent setting, especially if there is access to an MRI.

Nuclear Medicine

Nuclear Medicine uses a small amount of radioactive, injectable material to demonstrate the function of the brain.  It can be used to localize where seizures start. A scan before the seizure for a baseline image and then again with the radioactive material given during the seizure to locate activity in the brain.  This is not often used with HH, because by the time the nuclear medicine contrast is given and reaches the brain, the seizure has already moved out of the HH into the rest of the brain, giving false-localization results.

Ultrasound

Ultrasound of the brain uses sound waves to visualize the structures.  This is often used in infants under 6 months to see gross brain structures.  Older children and adults have fused skulls that block the sound waves.  No radiation in used in this test.  This is not often used with HH.

Task-based functional MRI (tb-fMRI)

Task-based functional MRI (tb-fMRI) is a relatively new type of test, which has FDA approval, and is broadly available.  Is shows where brain networks, such as those that control language or movement are located.  Generally, the patient needs to be awake and reliably able to perform tasks such as language testing while in the MRI machine.  In HH, it is not generally performed unless the team is concerned seizures are coming from somewhere besides the HH and want to know where brain networks are located near proposed seizure onset zones. 

Resting State functional MRI Resting State functional MRI (rs-fMRI)

Resting State functional MRI (rs-fMRI) is a relatively new type of test that locates all of the major brain networks.  Many major epilepsy centers are using this tool primarily for research in determining if it can help locate where seizures come from in the brain, whereas only a few are using it as part of mainstream clinical evaluation in epilepsy.  Only a single study in HH using rs-fMRI showed it was helpful in localizing where in HH the seizures came from and improved surgical outcomes (https://www.ncbi.nlm.nih.gov/pubmed/30374947).  Thus, the evidence is considered preliminary and such expertise is not expected to be available at most centers.

HH Lesion Types

Several attempts have been made to classify HH in order to better understand the characteristics and the impact the HH may have on the surrounding critical structures in that area of the brain. What type of HH you have will be a factor when deciding on a treatment plan.

To properly understand hypothalamic hamartomas, a distinction must first be made between the 2 different subtypes or classifications. They are: 1) intrahypothalamic (or sessile) and 2) parahypothalamic (or pedunculated).

The intrahypothalamic (or sessile) HH has a base of attachment within the third ventricle and can be either partial or complete. These lesions vary significantly in size but typically extend into the third ventricle itself and distort the surrounding anatomical structures, most importantly, the fornix or mammilary body. These structures are critical in the process of memory and behavior and therefore it is common for short-term memory and behavior disturbances to be evident. Sessile HH’s are most often associated with neurological issues and an initial presentation of gelastic seizures with a progression to other seizure types. Just under half of individuals with sessile HH’s will develop precocious puberty at some point in their lifetime. It is not unusual for children with this type of HH to experience a progressive decline in behavior, cognitive abilities, and social skills.

The parahypothalamic (or pedunculated) HH is more often associated with precocious puberty and not usually associated with epilepsy or neurodevelopmental problems. Treatment for these types of lesions is usually aimed at controlling the effects of the sexual development (precocious puberty) and premature bone development. Most cases can be easily classified into one category or the other, but some combinations of the two do exist.

HH is frequently Misdiagnosed

Symptoms ranging from mild to severe seizures can be difficult to recognize. Also, there may be other associated endocrine and behavior issues which may be the first symptoms addressed. In some cases, once the diagnosis of epilepsy or a seizure disorder is made, the next critical step of discovering an HH through high resolution MRI is missed. For some families, gelastic seizures are not readily recognized as a seizure and HH is misdiagnosed as colic, Irritable Bowel Syndrome (IBS), acid reflux, and/or behavioral issues. This can prevent a proper diagnosis and lead to the delay of treatment and in some cases, result in unnecessary procedures.

The importance of working with a medical team familiar with the complexities of HH cannot be overstated. Trust your instincts when dealing with the medical community and always ask questions.

Here are lists of of suggested questions you can print out and take with you to your neurologist, neurosurgeon and/or neuroradiologist.

Here are lists of of suggested questions you can print out and take with you to your neurologist, neurosurgeon and/or neuroradiologist.

Neurologist Questions

Neurosurgeon Questions

Neurosurgeon – Gamma Knife Surgery Questions

Neurosurgeon – Stereotactic Laser Ablation Questions

Make sure you understand their answers and be your own best advocate. You may have to make some very challenging decisions on your own behalf or that of your child. Ultimately, your treatment plan is up to you and the medical team you trust.