Unusual Clinical Manifestation Associated with Hypertrophic Olivary Degeneration

Hypertrophic olivary degeneration (HOD) is a rare abnormality that is caused by a lesion in the Guillain‐Mollaret triangle in the brainstem.1, 2 HOD usually occurs uni‐ and ipsilaterally to the lesion if the lesion is in the brainstem or contralaterally to the lesion if the lesion is in the cerebellum, as has been shown by MRI. The Guillain‐Mollaret triangle is composed of the contralateral dentate nucleus, the ipsilateral red nucleus, and the ipsilateral inferior olivary nucleus (ION). The ION is a highly developed complex that is the main source of climbing fibers to the cerebellum. These fibers have powerful excitatory synapses on Purkinje cell dendrites. The inferior olive tends to possess a slow, rhythmic, spontaneous activity. HOD usually manifests itself with palatal myoclonus.3, 4 The causes of HOD include trauma, inflammation, tumor, degenerative disease, and surgical manipulation. We describe a 52‐year‐old woman who developed an unusual clinical presentation associated with HOD.

Case Report

The patient's history started 4 months before she was admitted to our hospital, when she complained of subjective balance disturbances. A neurological examination performed in another hospital had been considered normal. A brain MRI revealed cerebral (right parieto‐occipital region and right and left temporal lobe at the subcortical level) and cerebellar (vermis, right cerebellar hemisphere, and the left cerebellar peduncle) metastases. MRI also showed a slightly increased T2 signal intensity in the right olivary nucleus. A total body CT detected lung cancer. She underwent resection of the cerebellar metastasis. After surgery, she presented gait ataxia and, approximately 20 days later, she progressively developed headache, dysarthria, an inability to walk as a result of ataxia, upper‐limb plegia, and involuntary head movements. No palatal myoclonus was observed. A ventricular derivation was performed, though to no beneficial effect. Upon admission to our department (approximately 40 days after surgery), she was in a stuporous state with bilateral upper‐limb plegia, as well as asynchronous involuntary head and jaw movements characterized by latero‐lateral oscillations of the head and jaw (see Video 1). The right eye was directed toward the right, whereas the left eye was in the primary position. Gaze could be oriented toward the verbal stimulus. The patient did not have nystagmus. Pursuit movements could not be assessed. The involuntary movements persisted for most of the day, increasing in intensity after verbal and tactile stimulation, but disappeared during sleep. Although we did not perform electromyography, a video recording allowed us to estimate that the frequency of the latero‐lateral oscillations was in the range of 2 to 3 Hz. EEG excluded epileptic abnormalities and documented regular physiological sleep features. Meningeal carcinomatosis and paraneoplastic syndrome were ruled out by the absence of neoplastic cells and cerebellar autoantibodies in the liquor. Brain MRI revealed increased T2 signal intensity in the right bulbar olivary nucleus (Fig. 1). Death resulted from nosocomial infection.

Figure 1.

T2 spin echo brain MRI scan before (A) and after (B) surgical removal of cerebellar metastasis showing hyperintensity of the right olivary nucleus.

Discussion

The novelty of this case report lies in the unusual clinical presentation associated with HOD. Involuntary movements in this patient involved the neck and jaw muscles, as opposed to the palatal muscles.2, 3, 4, 5 Patients with HOD are usually affected by palatal myoclonus or palatal tremor.1, 2 Upper‐limb tremor, upper‐limb dysmetria, and dysarthria may also be present.6 Holmes' tremor may therefore be associated with HOD, even in the absence of palatal myoclonus. We also assume that the presence of bilateral upper‐limb plegia in this case concealed limb tremor, which meant that head tremor alone was detected. To our knowledge, involuntary movements of the neck and jaw muscles, such as those we observed in our patient, have not previously been reported as associated with HOD. The movements, which were characterized by asynchronous activation of the neck and jaw muscles with a tremor‐like appearance, were present most of the day and only disappeared during sleep. MRI examination revealed T2 hyperintensity in the right bulbar olivary nucleus. Although no autopsy was performed, the MRI abnormalities were consistent with the clinical manifestations and course. The lack of contrast enhancement excluded the presence of metastatic lesions or infection, whereas hypertrophy of the ION excluded an infarction of the olivary nucleus.7

In the patient we describe, onset of ataxia apparently occurred a few days after surgery, worsening thereafter, whereas involuntary movements of the head and jaw started approximately 3 weeks later. Metastases in the left cerebellar peduncle are likely to have caused the dysfunction of the cerebello‐olivar circuit, whereas surgical removal may then have boosted the pathophysiological mechanisms leading to trans‐synaptic degeneration of the olivary nucleus. The fact that involuntary head and jaw movements did not start immediately, but approximately 3 weeks after surgery, suggests that the involuntary movements of the head and jaw were associated with trans‐synaptic degeneration of the olivary nucleus. This hypothesis is in keeping with radiological observations in previous HOD cases,8, 9 thus confirming that HOD develops approximately 1 month, or even later than 1 month,6 after lesions have damaged the Guillain‐Mollaret triangle. The metastatic lesion in our patient, which occurred in the left cerebellar peduncle, caused right olivary hypertrophy. Involuntary head and jaw movements in the patient we describe may therefore be associated with a disruption in the inhibitory projections from the deep cerebellar nuclei, through the central tegmental tract, to the inferior olive.1 Indeed, the blockade of cerebellar inhibition and the consequent denervation hypersensitivity of the olivary neurons have been reported to cause olivary hypertrophic degeneration and induce synchronized oscillation of large groups of ION neurons.10

Consent

Written informed consent was obtained from the patient's relatives for publication of this case report and any accompanying images and video.

Author Roles

(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique.

J.F.: 1C, 3A

A.C.: 1C, 3A

C.C.: 3B

A. Bozzao: 3B

A. Berardelli: 1A, 3B

G.F.: 1B, 3B

Disclosures

Funding Sources and Conflicts of Interest: The authors report no sources of funding and no conflicts of interest.

Financial Disclosures for previous 12 months: Prof. A. Berardelli received research grants from Allergan, Lundbeck, Merz, and UCB. Prof. G. Fabbrini received research support from Allergan, Lundbeck, and Novartis.

Supporting information

Video 1. Involuntary head and jaw movements characterized by latero‐lateral oscillations of the head and jaw.