The range of cognitive functioning in patients with HH

Author: John F. Kerrigan, MD, Co-Director, Hypothalamic Hamartoma Program Barrow Neurological Institute

Patients with hypothalamic hamartomas (HH) certainly struggle with seizures, but many also have problems with learning and other domains of intellectual (or cognitive) functioning. This column focuses on recent research that addresses the range of cognitive functioning in patients with HH.

Research papers describing the clinical features of children and adults with HH have been published sporadically since the 1950’s, but the first comprehensive description of the clinical symptoms and natural history associated with HH and epilepsy was published by Dr. Samuel Berkovic and his colleagues in 1988. The exact reference is provided at the end of this column. For those interested in jumping into the medical literature on HH, this is an excellent place to start. [Remember, peer-reviewed research papers are written to communicate with other researchers and health professionals, and may not be easy reading for those without a medical background.]

Dr. Berkovic’s paper is remarkable for capturing so many of the important features of the HH experience from a series of only four patients. Some of their observations include that fact that young children with HH often have only gelastic seizures until they reach early school age, and then other seizure types (or multiple seizure types) may then develop, which are much more disabling for the patient and family. There is a substantial risk of developmental delay (or even loss of previously learned skills), usually when seizures worsen. And, seizures associated with HH are usually not controllable with our available anti-epilepsy drugs (AEDs).

Like many research papers that are the first to report the key clinical features of a particular illness, the paper by Berkovic and colleagues describes the problems of more severely affected HH patients. [This is referred to as “ascertainment bias”, in which referral centers see the most severely affected portion of the patient population, and therefore fail to appreciate milder forms of the illness.] Since 1988, experience with much larger numbers of patients has revealed the range of severity associated with HH and epilepsy, including patients who can be controlled with AED medications, patients who may reach adulthood having only gelastic seizures, and patients who have very little cognitive difficulties.

George Prigatano, Ph.D. and his colleagues have recently published a research paper examining the neuropsychological test scores of 49 patients with HH and epilepsy, who were undergoing evaluation for possible surgery at the Barrow Neurological Institute in Phoenix. This study includes patients between the ages of 5 and 55 years. The strength of this study is the large number of patients, enabling the investigators to evaluate a more representative spectrum of patients with HH and epilepsy. The weaknesses of this study include the fact that patients under 5 years of age were not cognitively evaluated (Barrow did not have the capability to reliably test children less than 5 years at the time this study was done). Additionally, patients were evaluated only at one time point in this report, and consequently the changes in cognitive functioning that may occur over time in some HH patients can be missed in this type of study. Nevertheless, this is by far the largest study describing neuropsychological functioning in HH patients to date.

There are two findings from this study that deserve specific mention. This report confirms the tremendous diversity in cognitive functioning among patients with HH and epilepsy. Neuropsychological scores occurred in a smooth continuum, but Prigatano and colleagues grouped the patients into one of four categories: 1) patients who are functioning at a normal level [35% of the entire study group], 2) patients with significant deficits in either verbal or non-verbal domains, but with overall scores within the normal range for intelligence [18%], 3) patients whose scores place them into a testable but severely impaired category [33%], and 4) those who were so severely impaired that actual testing could not be completed [14%]. It is important to note that individual patients within the best-performing category may still struggle in specific areas of testing, such as processing speed or short term memory.

Prigatano and colleagues also examined what clinical factors might be associated with lower neuropsychology testing results. That is, what might be the cause of the lower scores? Statistical methods to look for significance were utilized and a number of different clinical factors, such as the patient’s age, were evaluated (statistical significance suggests that the association is not due to chance).

The number of anti-epilepsy drugs (AEDs) taken at the time of testing was the single most powerful predictor for lower scores (a higher number of AEDs tended to be associated with lower scores). Even this raises additional research questions, however, since the number of AEDs may contribute to over-medication (and decreased cognitive functioning on neuropsychology testing) or the number of AEDs may be a proxy for the severity of the epilepsy and the number of seizures (patients with more frequent and severe seizures are more likely to take more medication). Or, of course, perhaps both are true. The size of the HH lesion also appears to be important (a patient with a large HH is more likely to have lower scores). Other factors will undoubtedly be shown to be important predictors as we learn more about HH and epilepsy.

(Disclosure: I am one of the authors of the research paper by Dr. Prigatano and colleagues.)

References:

Berkovic SF, Andermann F, Melanson D, Ethier RE, Feindel W, Gloor P. Hypothalamic hamartomas and ictal laughter: evolution of a characteristic epileptic syndrome and diagnostic value of magnetic resonance imaging. Ann Neurol 1988;23:429-439.

Prigatano GP, Wethe JV, Gray JA, Wang N, Chung S, Ng Y-t, Prenger E, Kerrigan JF. Intellectual functioning in presurgical patients with hypothalamic hamartoma and refractory epilepsy. Epilepsy Behav 2008;13:149-155. To see this article in its entirety, click here.