Radiation to the cervical spine is a known cause of Lhermitte's sign. Leung et al. report an incidence as high as 10.3% in patients receiving non-IMRT for nasopharyngeal cancer [3
]. This incidence may be higher than that seen in other head and neck sites due to the nature of radiotherapy for nasopharyngeal tumors and the close proximity of disease to the cervical spinal cord. Fein et al. report an overall incidence of 3.6% of LS in 1112 patients receiving at least 30
Gy to at least 2 cm of cervical spinal cord [4
]. Chemotherapy such as cisplatin has also been reported to cause LS [5
], and this may have contributed to the development of LS in our case. Total radiation dose and fraction size may play a role in the risk of developing LS. Fein and colleagues describe patients receiving ≥200
cGy per fraction (one fraction per day) or ≥5000
cGy total dose to the CSC having an increased risk of developing LS. Leung finds a higher incidence of LS in patients requiring bilateral neck-boost irradiation. In these patients, the spinal cord dose was greater than 49.8
Gy and there was an 11.5% incidence of LS. This is compared with patients receiving no neck boost where the spinal cord dose was 46.8
Gy and the incidence of LS was 7.2%. However, Million and Cassisi state that total spinal cord doses as low as 3000
cGy with fractions sizes of 120
cGy may produce mild symptoms of LS [7
]. With the introduction of IMRT, we have been able to deliver more conformal radiation doses to patients with head and neck cancer. We have seen 3 cases of LS develop after head and neck IMRT for 291 patients, the other two cases with much milder symptoms. Our case report patient received a cord maximum dose of 4478
cGy with 128
cGy maximum dose to the cord daily. With the conformal dose of IMRT, the mean cord dose was only 2692
cGy. In non-IMRT, opposed lateral fields are frequently utilized resulting in a much more homogeneous dose distribution to the spinal cord. Reviewing four studies where patients were treated with non-IMRT, the maximum cord dose was similar to ours at 4716 (±770
cGy) but the mean cord dose was much higher at 4026 (±425
]. Our experience of LS developing in 1% of our head and neck IMRT cases suggests that IMRT may result in a lower incidence of LS, certainly lower than the 10.3% reported by Leung and colleagues and lower than the 3.6% seen by Fein et al.
The time to development of LS in our patient of four months after chemoradiation is similar to the time to symptoms reported by Fein (mean, three months) and Leung (median, three months). Our patient's symptoms lasted approximately nine months also in line with the duration of symptoms reported by Fein (mean, six months) and Leung (median, seventeen weeks).
Jones hypothesizes that the pathophysiology of radiation-induced LS is the result of transient demyelination [9
]. He believes that radiation inhibits normal proliferation of oligodendroglial cells which produce myelin. Without the myelin, the exposed sensory neurons become vulnerable to irritation from neck flexion causing electric-shock sensations. Eventually, the oligodendroglial cells recover from radiation, more myelin is produced, and the symptoms of LS abate.
Using IMRT, a much different radiation dose distribution is delivered to the spinal cord than with non-IMRT opposed lateral radiotherapy. Rather than a homogeneous dose distributed throughout the cord, there is a dose gradient with most of the radiation delivered anteriorly.compares the spinal cord dose distribution seen in our IMRT case with the same patient if he were treated via a non-IMRT opposed laterals technique. Butler et al. hypothesized that the dorsal columns served as the radiation target leading to LS [11
]. Given the development of LS in our patient and the more anterior radiation dose distribution seen with IMRT, we suggest a more anterior spinal cord tract as the target for IMRT-caused LS. As first mentioned by Jones, we hypothesize that irradiation of the spinothalamic tract, which recognizes simple touch, pain, and temperature, is the cause of LS for our patient ().
Figure 2 Radiation dose distribution represented by radiation isodose lines through an axial plane of the cervical spinal cord. (a) Dose distribution with IMRT and (b) dose distribution using a non-IMRT plan using opposed lateral beams. The light blue line (more ...)
Spinal cord anatomy. The anterior spinothalamic tracts are hypothesized to be the target of IMRT-caused LS and are highlighted in gray.