Subdural Hematoma as a Serious Complication of Huntington’s Disease: An Observational Study

INTRODUCTION

Subdural hematoma (SDH) represents accumulation of blood in the space between the dura and the arachnoid. It is most frequently caused by head trauma leading to stretching and tearing of veins within that space. It was first identified in the 17th century, described pathologically by Virchow in the mid-19th century and studied more extensively by Putnam, Cushing, and Wantanabe in the 20th century [1]. There is epidemiological evidence that its occurrence is increasing presumably related to the increasing average age of the general population [2]. Known risk factors include age, male gender, head trauma (which may be mild), underlying cerebral atrophy (as seen in dementia such as Alzheimer’s disease) anti-coagulation, underlying intrinsic bleeding disorders and a variety of cerebral vascular diseases [3–7].

Huntington’s disease (HD) patients are also at increased risk for SDH because of general brain atrophy, frequent falls, and frequent head bumping. However, this association is rarely, if ever, mentioned in general reviews or even comprehensive texts of HD. In the modern era since the discovery of the HD gene there have been only a few anecdotal case reports of this association [8] and two brief summaries of four [9] and seven cases respectively [10]. Features of SDH which generally lead to an urgent diagnostic workup such as cognitive change, focal weakness or gait instability can be subtle, particularly in individuals such as HD patients who already have fixed neurological changes due their neurodegenerative disease. Because the occurrence of SDH in HD is likely to be under-recognized and because its occurrence can be a major cause of medical care and disability, we review our experience with this important association.

METHODS

We performed a retrospective chart review of patients with HD known to have sustained subdural hematoma and seen at three Huntington’s Disease Society of America (HDSA) Centers of Excellence: University of Washington (UW), Oregon Health and Science University (OHSU), and UC Davis (UCD). We attempted to identify all occurrences of SDH in patients with manifest (symptomatic) HD seen in the above clinics over multiple years: 2007–2020 at UCD and 2010–2020 at OHSU and UW. In those time periods there were 8 cases of SDH at UCD in 468 patients, 5 cases of SDH at OHSU in 225 patients, and 10 cases of SDH at UW where the exact number of HD patients seen in that period could not be accurately determined but was estimated to be approximately 500. Two additional cases of SDH seen prior to 2010 at the UW were also included because of important clinical findings. It is important to note that this was an observational study based on anecdotal identification of cases. It was not a formal epidemiological study because time frames and population sizes varied and could not be accurately determined. In addition, the diagnosis of SDH was always made in a clinical setting other than the HD clinics, so a systematic identification of SDH using the electronic medical record of HD patients seen in these clinics could not adequately identify cases of SDH in HD. Unified Huntington Disease Rating Scale (UHDRS) Motor Scores closest to onset of SDH were recorded when available. Genetic testing with CAG repeat expansion size was available in 22 patients. These record reviews were approved by the relevant institutional IRBs.

RESULTS

Twenty-five patients with HD and subdural hematoma were identified. The characteristics of these individuals are summarized in Table 1. There were 9 men and 16 women with a mean CAG repeat expansion size of 43 (range 39–46). The mean age at the time of the SDH was 60 years (range 36–89) averaging approximately 8 years following the onset of HD-related symptoms. Most patients had moderate to marked chorea and motor disability with average UHDRS motor score of 51 (range 5–95, 16 patients). Nineteen of the 25 patients had a history of mild to moderate head trauma within the previous few days. One patient (Case 5) was known to have had frequent falls but had no known fall or head trauma in the week preceding the SDH. Another patient (Case 4) had no head trauma but fell when descending stairs and slid down several steps on her buttocks. The most common symptoms associated with SDH were altered mental status manifesting as confusion, unilateral weakness, and loss of consciousness. The SDH was unilateral in 13 patients and bilateral in the other 12. Notably, additional complications occurred in 2 patients. Patient #3 sustained a left temporal intraparenchymal hemorrhage in addition to a small right SDH following a fall when trying to enter a bus. Patient #10 developed a left frontal parenchymal hematoma (in addition to an SDH) during a fall from a recreational vehicle with subsequent development of a seizure disorder requiring anti-seizure medication.

CT brain imaging of a typical unilateral SDH is shown in Fig. 1 as well as an image of severe bilateral SDH (Case 5). Nineteen patients required inpatient hospitalization and 16 required a neurosurgical procedure (usually multiple burr holes).

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Fig. 1

A) Right sided SDH in Patient 4. B) Left temporal intraparenchymal hematoma in Patient 3 who also had a small right sided SDH. C) Large bilateral SDH in Patient 5. D) Bilateral dural membranes containing blood obtained at brain autopsy in Patient 5.

It is worth mentioning the details of several patients to demonstrate the variety of risk factors, the potential seriousness, and manifestations of this phenomenon.

Two of the patients (Cases1 & 5) died in association with the SDH. Both of these SDHs were bilateral and both had evidence of recurrence. Patient #1 had bilateral burr holes following her fall and was discharged to home. However, two weeks later she had another more severe fall with recurrent bilateral SDH associated with coma. A decision was made not to repeat surgery and she died. Patient #5 developed bilateral weakness and confusion and, although he had no known recent head trauma, he had a moderate to severe movement disorder and was known to often bump his head on the wall. Large bilateral SDH were noted on CT images (Fig. 1). The SDHs were drained and partially evacuated through bilateral burr holes. Repeat CT images revealed reduction in the size of the original SDH but recurrence of two smaller hematomas. During the hospitalization the patient developed severe bilateral aspiration pneumonia and died.

Patient #6 was taking Coumadin for atrial fibrillation, which undoubtedly increased his risk for bleeding.

Patient #9 had the smallest CAG repeat size (39) with onset of symptoms at age 60 and fell from a motorized skateboard on a golf course.

The two oldest patients had recurrent SDH. Patient #14 had late onset disease (onset age 80, CAG 40) and sustained two SDH within a few days, and a third SDH from a fall 2 years later at age 88. Patient #13 was also elderly (86 years) and sustained 2 separate SDH 3 years apart.

Of note, a patient excluded from the study was a 55-year-old man with onset of HD related symptoms at age 37. At age 28 he had sustained a SDH in a motorcycle crash while intoxicated. It could not be determined if this event was related to the later onset of his HD symptoms.

DISCUSSION

This study was able to identify 25 HD patients sustaining a SDH which attests to the frequency of significant head trauma in this population. We estimate that SDH can occur in up to 2% of the manifest HD population, but clearly a more formal investigation is needed to refine this estimate. This finding should not be surprising since falls are common in HD. Because of truncal and head chorea persons with HD may injure their heads even without falling. Furthermore, impaired judgement, impulsivity and lack of awareness may induce persons with HD to take inappropriate risks. Detailed assessment of these functional problems was not available for the patients in this study. Also, essentially all manifest HD patients are on a variety of medication that can potentially affect mental status and motor performance. Presenting symptoms of SDH include unilateral weakness, confusion and altered mental status, headache, gait disorder, seizure, lethargy, and coma. Severity of the clinical syndrome depends on factors such as size of SDH, unilateral versus bilateral, recurrence, patient age and associated co-morbidities [11]. SDH often requires surgical intervention with decompression and removal of blood products. A minority of cases can be closely followed with medical observation (5–25%) but may eventually require surgical intervention.

Many of the patients in our study had 8–10 years or more of HD symptoms, although 9 (#4, 7, 9, 11, 14, 16, 17, 22, 23) had been symptomatic for only 0–6 years. Eleven of 16 patients had a UHDRS Motor Score greater than 40, indicative of considerable motor impairment increasing the risk of falls. One patient was asymptomatic and another 5 patients were observed without surgical intervention. However, 17 patients required surgery which always results in hospitalization and may be associated with $50,000 or more of medical care costs [12]. An insurance company refused to cover the hospital costs for one patient claiming that HD was a “preexisting condition.” The potential seriousness of SDH occurrence in HD is emphasized by the two deaths in our series.

In terms of anatomy, persons with HD are at increased risk for SDH because of underlying cerebral atrophy. One patient in our series had a previous neurosurgical procedure from fetal brain transplant which is a reported risk factor for subsequent SDH [13]. It is possible that there is even an underlying vascular abnormality in HD [14].

It is of interest that 16 of our 25 patients (64%) were female, whereas SDH is usually reported as being much more frequent in males (74% males in a recent study [15]). The reasons for this excess of females is unknown. It is possible that women with HD are more liable to fall than men and/or sustain more physical damage during a fall. Two studies have found some evidence that disease severity and progression of HD is increased in females compared with males [16, 17]. These issues require additional investigation.

It seems likely that other progressive neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and cerebellar ataxia also increase the risk of SDH. However, we were unable to find a systematic study of this association in other similar diseases. A relevant study in Italy found that the consequences of SDH were more severe in patients with Parkinsonism or dementia compared with patients who had neither of these syndromes [18].

Because this was not a formal epidemiological study there could be no accurate determination of the incidence or frequency of SDH in this HD population. Although our results suggest that about 2% of the manifest HD population may experience a SDH (23/∼1,190), a more focused and systematic study is required.

In conclusion, while not a formal epidemiological study, our retrospective review provides compelling anecdotal evidence that there is an increased risk of SDH in HD even in the absence of head trauma. While further investigation to elucidate risk of SDH in HD is needed, any HD patient noted to have new onset headache, unilateral weakness, or abrupt confusion or lethargy requires immediate medical attention with radiographic head imaging whether or not there is a history of recent head trauma. Educating patients and their care givers about the risk of SDH and providing gait assessment and training should become standard practice in clinics providing care for the HD population. Furthermore, efforts should be made to spread awareness of this phenomenon to providers in other disciplines, particularly those in the primary care and urgent care settings.