Proton magnetic resonance spectroscopy of the thalamus in patients with osteoarthritis of the hip

Article focus

The purpose of our study was to assess the functional change of the thalamus in patients with osteoarthritis of the hip using proton magnetic resonance spectroscopy.

Key messages

The ratio of N-acetyl aspartate to creatine plus phosphocreatine in the thalamus contralateral to the symptomatic hip in the patients with osteoarthritis of the hip was significantly lower than the ratio of N-acetyl aspartate to creatine plus phosphocreatine in the thalamus in control patients. We also detected a strong negative correlation between the N-acetyl aspartate of the thalamus contralateral to the symptomatic hip in patients with osteoarthritis when compared with the duration of pain.

Strengths and limitations of the study

This is the first study to our knowledge to assess the changes of N-acetyl aspartate in the thalamus in patients with osteoarthritis of the hip using proton magnetic resonance spectroscopy. The limitations of this study are that we only evaluated a small number of patients and that it was not a longitudinal study.

Introduction

Osteoarthritis (OA) is one of the most common causes of chronic pain, affecting many different joints including the hip. The prevalence of OA of the hip is estimated to be 7.4% in the elderly population,¹ and this is expected to rise alongside ageing populations.² However, to our knowledge, the pathomechanism of OA of the hip has been never clarified. Gwilym et al³ reported the atrophy of the thalamus contralateral to the symptomatic hip joint in patients with OA using voxel-based morphometry, which is a method of assessing the volume of brain gray matter using high-resolution three-dimensional (3D) MRI. The study also showed a reversal of thalamic atrophy after arthroplasty of the affected hip, alongside an associated decrease in pain and increase in function.³ These findings revealed that the morphological changes of the thalamus have an important role for pathomechanism of chronic pain.

Proton magnetic resonance spectroscopy (¹H-MRS) is a non-invasive method of measuring concentrations of intracellular metabolites with MRI. The main metabolites detected by ¹H-MRS in the central nervous system are N-acetyl aspartate (NAA), creatine plus phosphocreatine (Cr), choline-containing compounds (cho), and myoinositol (mI). NAA is located primarily in neurons, and its concentration is considered to reflect neural activity or function.^4,5 Several studies have reported decreased levels of NAA in patients with herpes simplex encephalitis,⁶ Alzheimer’s disease,^7,8 steno-occlusive carotid artery disease,⁹ epilepsy,¹⁰ acute traumatic brain injury¹¹ and stroke.^12,13 Decreased levels of NAA were also observed in the thalamus of patients with chronic pain. Fukui et al¹⁴ reported a decreased concentration of NAA in the thalamus in patients with neuropathic pain, and Pattany et al¹⁵ reported that the concentration of NAA in the thalamus were significantly lower in patients with pain after spinal cord injury than patients without pain. These studies suggest that functional changes of the thalamus contribute to the pathomechanism of chronic pain. Thus, we hypothesised that a functional change of the thalamus would be observed in patients with OA of the hip.

The purpose of our study was to assess the functional change of the thalamus in patients with OA of the hip using ¹H-MRS.

Materials and Methods

Results

The clinical characteristics of the nine patients with OA of the hip are shown in Table I. The mean duration of pain was 3.5 years (1.1 to 7.0) and the mean VAS pain score was 6.1 (1.2 to 9.0). The MRS data of the OA and control groups are shown in Table II and Table III, respectively. The mean ratio of NAA to Cr in the control group was 1.630 (1.267 to 2.038) for the right thalamus and 1.592 (1.120 to 1.880) for the left thalamus, which did not reach statistical significance (Mann-Whitney U test, p = 0.89). The NAA to Cr ratio for the two sides were therefore averaged and used as a control value. The mean NAA to Cr ratio of the contralateral thalamus to the symptomatic hip in the patients with OA were significantly lower than those of the thalamus in the control group (1.355 (1.043 to 1.502) versus 1.611 (1.194 to 1.882), p < 0.001). There was no significant difference between the mean NAA to Cr ratio of the thalamus contralateral to and the thalamus ipsilateral to the symptomatic hip joint in the patients with OA of the hip (1.355 (1.043 to 1.502) versus 1.430 (1.087 to 1.875), p = 0.69). No correlation was identified between the mean ratio of NAA to Cr of the thalamus contralateral to the symptomatic hip in the patients with OA of the hip and VAS (Fig. 1, p = 0.89). A strong negative correlation was observed between the mean ratio of NAA to Cr in the thalamus contralateral to the symptomatic hip in the patients with OA of the hip and pain duration (Fig. 2, r = -0.83, p = 0.018).

Fig. 1

Scatter graph showing the relationship between the ratio of NAA to Cr in the thalamus contralateral to the symptomatic hip in patients with osteoarthritis of the hip and pain as measured by a visual analogue scale (VAS). No correlation was identified between the ratio of NAA to Cr and VAS.

Fig. 2

Scatter graph showing the relationship between the ratio of NAA to Cr in the thalamus contralateral to the symptomatic hip in patients with osteoarthritis of the hip and the duration of pain. A significant negative correlation between the ratio of NAA to Cr and pain duration was observed (r = -0.82, p = 0.044).

Discussion

The present ¹H-MRS data suggested that the ratio of NAA to Cr in the thalamus contralateral to the symptomatic hip in the patients with OA of the hip were significantly lower than the ratio of NAA to Cr of the thalamus in the control group (p < 0.001). In addition, a strong negative correlation was observed between the ratio of NAA to Cr of the thalamus contralateral to the symptomatic hip in the patients with OA of the hip and duration of pain (r = -0.83, p = 0.018).

There have been several studies which revealed that functional changes of the thalamus contralateral to the symptomatic side in chronic pain patients. Iadarola et al²² reported that the activities of the thalamus contralateral to the symptomatic side were decreased in patients with neuropathic pain when using positron emission tomography. Fukumoto et al²³ reported that hypoperfusion of the thalamus contralateral to the symptomatic side were observed in long-term patients with reflex sympathetic dystrophy syndrome (RSDS) by using single photon emission computed tomography (SPECT). The present study suggested the decrease of NAA levels in the thalamus contralateral to the symptomatic hip in patients with OA of the hip. Fukui²⁴ reported on the relationship between the ratio of NAA to Cr in the thalamus measured by ¹H-MRS, and regional cerebral blood flow in the thalamus measured by stable xenon-enhanced computed tomography. Our study indicated functional changes of thalamus contralateral to the symptomatic hip joint in patients with OA of the hip. This is the first study to evaluate the thalamus of patients with OA of the hip using ¹H-MRS.

The relationship between pain intensity and functional change of the thalamus is controversial. Fukumoto et al²³ reported that pain intensity was not correlated with contralateral thalamic perfusion in patients with RSDS by a SPECT study, although Pattany et al¹⁵ showed that pain intensity was negatively correlated with the concentration of NAA in the thalamus in patients with spinal cord injury in a study using ¹H-MRS. In accordance with the study of Fukumoto et al,²³ no correlation was observed between the ratio of NAA to Cr in the thalamus and the VAS for pain in this study.

We hypothesised that a correlation existed between a decrease in NAA and the duration of pain. In agreement with our hypothesis, the ratio of NAA to Cr of the thalamus contralateral to the symptomatic hip in the patients with OA of the hip was negatively correlated with duration of pain. Fukumoto et al²³ also suggested that a decrease of the contralateral thalamic uptake index was correlated with the time since onset on the basis of a SPECT study. These results suggested that duration of pain was associated with a functional change in the thalamus.

The present study has several limitations. First, the mean age of the patients with OA of the hip was higher than that of the control group (61.4 vs 30.0, p < 0.001). This difference may have resulted in an age-dependent difference in the ratio of NAA to Cr. However, several studies have shown that metabolic changes in the brain associated with aging occur almost entirely within the first two years of life^25-27; only minimal changes occur thereafter, and adult concentrations are achieved by the age of 20 years.²⁸ Furthermore, Fukui et al¹⁴ reported the MRS data of 14 healthy volunteers with an age range between 23 and 64 years and found no age-related change in the mean NAA concentration. Thus, the age difference between the two groups in our study is unlikely to account for the observed metabolic changes. Second, the patients who participated in this study were all women. No men with OA of the hip participated. Thus, further analysis is required to clarify the existence of any potential gender-related differences in the ratio of NAA to Cr in patients with OA of the hip. Third, only a small number of patients were evaluated. Further studies are required to determine whether the present findings remain valid in a larger population. Finally, we were not able to repeat ¹H-MRS after surgery, due to artefacts induced by total hip arthroplasty implants.

Conclusion

The ratio of NAA to Cr were lower in patients with chronic hip pain, suggesting an association between chronic hip pain and functional changes in the thalamus. ¹H-MRS can be used to detect decreased thalamic neural activity in clinical practice. Future studies will be important for understanding whether or not the decreased ratio of NAA to Cr can be resolved by surgical or pharmacological treatment.