Holmes tremor was originally described by Benedikt and Souquesso and then by Holmes in 1904 who reported a patient with midbrain lesion and a
3-5 Hz tremor that was present at rest and increased markedly during intentional movement or with certain sustained postures [
2,
3]. There have been several terms used in the literature to designate this unique tremor. Using the terms "Holmes tremor", "midbrain tremor", "myorhythmia", "thalamic tremor", "mesencephalic tremor" and searching through Medline, we found only 5 cases of Holmes tremor complicating cerebral toxoplasmosis in AIDS patients. Mattos et al reported one case of midbrain toxoplasmosis and one case of midbrain and cerebellar toxoplasmosis [
4] while Koppel [
5] described a case with midbrain lesion. Strecker and al [
6] reported on a case of mesencephalic toxoplasmic abscess involving the red nucleus and extending to the cerebellar peduncle. In the case reported by Pezzini [
1], multiple nodular lesions were found in the post-central gyrus, in the right frontal superior gyrus, in the inferior parietal lobule and more importantly in the thalamus extending to the midbrain. There is one report of a patient with Holmes' tremor and toxoplasmic abscess in the left posterior thalamic region and in the posterior arm of the internal capsule [
7]. Our case has two specific features: there was an abscess in the thalamus and the internal capsule with extensive edema involving the midbrain and the very short delay from initial neurological deficit to tremor onset. Because in our patients, the postero-lateral thalamus was involved, the cortico-thalamic tracts may have therefore been damaged. In all cases of Holmes tremor in AIDS patients with cerebral toxoplasmic abscess reported in the literature, various anatomical locations of brain abscesses were associated with Holmes tremor (Table
1). The unifying feature of all these observations is the involvement of either the cerebello-thalamo-cortical and/or the dentato-rubro-olivary pathways. Involvement of the same tracts have also been reported in Holmes tremor due to other causes, especially those secondary to vascular or brain traumatic lesions [
3]. In our patient, the role of a superimposed dysfunction of the nigrostriatal system either by the abscess in the internal capsule or surrounding edema may account for the rest component, although it remains hypothetical as in the case reported by Micheli [
2,
3]. The nigrostriatal system was not involved in all reported cases of toxoplasmic-related Holmes tremor. There is one report of DaTSCAN SPECT study in AIDS and Holmes tremor related to a toxoplasmic abscess [
6]. The author showed that there was a left-sided reduction of dopamine transporter 4 months following a treatment of cerebral toxoplasmosis. Recently, in a retrospective DaTSCAN SPECT study of six patients with Holmes tremor, there was no remarkable visual difference in presynaptic dopaminergic nigrostriatal system involvement. The authors concluded that nigrostriatal pathway damage may not be crucial for the development of Holmes tremor [
8]. Finally, it is also possible that direct HIV- infections of neural cells in these pathways play a modulatory pathophysiologic role thus explaining why not all patients with cerebral toxoplasmosis (which predominantly involves basal ganglia) develop Holmes tremor.
Table 1
Cases of Holmes tremor in patients with AIDS and cerebral toxoplasmosis.
Lekoubou A, | - Right posterior thalamus - Internal capsule | Yes | No/hypothetical |
Strecker K, 2006
| - Left midbrain | Yes | Yes |
Pezzini A, 2002
| - Left frontal superior gyrus, - Inferior parietal lobule, - right thalamus, - right midbrain | Yes | Yes |
Mattos JP, 2002
| - Left midbrain - Left cerebellar hemisphere | Yes | Yes |
Micheli F, 1997
| - Left posterior thalamus - Posterior arm of internal capsule | Yes | No/Hypothetical |
Koppel S, 1990
| - Left midbrain - Left frontal white matter | Yes | Yes |
In our patient, the delay from initial neurological deficit to the onset of tremor was only eighteen days. In previous reports, this delay (when available) ranged from 1 month to 5 months [
4‐
7]. The role of a secondary degeneration in the mechanisms of tremor has been advocated as it usually arises as a delayed manifestation of the initial lesion [
3]. In our observation and in that of Mattos [
4], tremor occurred within one month of initial neurological deficit. Unlike other cases of Holmes tremor including those related to toxoplasmic abscess, in these two cases, there was a dramatic improvement of the tremor while on antitoxoplasmic/steroid treatment. It is likely that in our case, neuronal integrity was restored before degeneration was initiated and very unlikely that the improvement could have occurred spontaneously as reported cases of spontaneous relief occurred within one year of tremor onset [
9].