Recovery of an injured anterior cingulum to the basal forebrain in a patient with brain injury: a 4-year follow-up study of cognitive function

Abstract

{Table 1} The patient′s 4-month DTT showed discontinuations of the anterior cingulum. Because the cingulum is known to be vulnerable to ICH in the opposite hemisphere, we think the injury of the left anterior cingulum might be due to the ICH rather than meningioma (Kwon et al., 2014). [...]using DTT, long-term recovery of an injured cingulum was demonstrated in a patient with brain injury. [...]because this study was conducted retrospectively, we were not able to obtain detailed neuropsychological data, except for MMSE. [...]studies without these limitations should be encouraged.

The cingulum, a long neural tract extending from the orbitofrontal cortex to the medial temporal lobe, obtains cholinergic innervation from three cholinergic nuclei in the basal forebrain (the nucleus basalis of Meynert [Ch 4], the medial septal nucleus [Ch 1], and the vertical nucleus of the diagonal band [Ch 2]), and is the passage of the medial cholinergic pathway which supplies cholinergic innervation from the basal forebrain to the cerebral cortex (Folstein et al., 1975; Selden et al., 1998; Lucas-Meunier et al., 2003). Therefore, it is important for cognition, especially memory function (Selden et al., 1998). In this study, using DTT, changes of the anterior cingulum were observed in a patient with brain injury (meningioma and ICH).

A 66-year-old male patient underwent craniectomy and removal of meningioma and concurrent intracerebral hemorrhage (ICH) at a neurosurgery department of a university hospital ([Figure 1]A). He was transferred to a rehabilitation department of another university hospital in order to undergo rehabilitation at 4 months after onset. The patient received comprehensive rehabilitative therapy including cognitive therapy which was performed 30 minutes/day and 5 times per week for 1 month. His rehabilitation continued until 4 years after onset at outpatient clinic of the rehabilitation department of our hospital (30 minutes/day and twice per week). Brain MRI scans performed at 4 months and 4 years after onset showed leukomalactic lesions in the right frontal area ([Figure 1]A). At the beginning of the rehabilitation, the patient showed mild cognitive impairment with a score of 22 on the Mini-Mental State Examination (MMSE, full score: 30, cut-off score < 24) (Folstein et al., 1975). By contrast, at 4 years after onset, his cognitive impairment had improved to a score of 28 on MMSE. The patient and his wife provided signed, informed consent, and our institutional review board approved the study protocol.{Figure 1}

Diffusion tensor imaging data were scanned twice (4 months and 4 years after onset) using a a 1.5 T Philips GyroscanIntera (Philips, Ltd., Best, the Netherlands) with single-shot echo-planar imaging. Imaging parameters were as follows: acquisition matrix = 96 × 96, reconstructed to matrix = 192 × 192, field of view = 240 × 240 mm2 , repetition time = 10,398 ms, echo time = 72 ms, and a slice thickness of 2.5 mm. Each diffusion tensor imaging replication was intra-registered to the baseline "b" images to correct for eddy-current distortions and head motion effect, using a diffusion registration package (Philips Medical Systems). Fiber tracking was performed using Philips Extended MR Work Space 2.6.3 based on the fiber assignment continuous tracking algorithm. The cingulums were reconstructed using two regions of interest on the color map of coronal images (green color: middle and posterior portion of the cingulum) with fractional anisotropy < 0.15 and an angle change > 27° (Concha et al., 2005).

On 4-month diffusion tensor tractography (DTT), discontinuations of both anterior cingulums were observed. By contrast, on 4-year DTT, the left cingulum was elongated to the left basal forebrain without significant change of the discontinued right cingulum ([Figure 1]B). Regarding the DTT parameters, fractional anisotropy, mean diffusivity, and tract volume were summarized in [Table 1].{Table 1}

The patient′s 4-month DTT showed discontinuations of the anterior cingulum. Because the cingulum is known to be vulnerable to ICH in the opposite hemisphere, we think the injury of the left anterior cingulum might be due to the ICH rather than meningioma (Kwon et al., 2014). On 4-year follow up DTT, the left anterior cingulum was elongated to the basal forebrain containing the three cholinergic nuclei (Ch1, Ch 2, and Ch 4) and tract volume on 4-year DTT showed the increment compared to that on 4-month DTT, however, no significant change was observed in the right cingulum (Selden et al., 1998; Nieuwenhuys et al., 2008). This finding appeared to indicate recovery of the left injured cingulum and it appeared that the improvement of the cognitive impairment in this patient (MMSE: 22 [4 months] → 28 [4 years]) was ascribed, at least in part, to recovery of the left injured cingulum.

In conclusion, using DTT, long-term recovery of an injured cingulum was demonstrated in a patient with brain injury. However, the limitation of DTT should be cautioned: a voxel in a multiple orientation cannot present full reflection of the underlying fiber architecture, resulting in possible underestimation of the neural tracts (Yamada et al., 2009). In addition, because this study was conducted retrospectively, we were not able to obtain detailed neuropsychological data, except for MMSE. Therefore, further studies without these limitations should be encouraged.

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, No. 2015R1D1A4A01020385.[7]