HOD is a rare form of multisynaptic and transneuronal degeneration of the inferior olivary nucleus, which usually develops secondary to the impairment of the dentato-rubro-olivary pathway in the Guillain–Mollaret triangle [4]. The oliva is located in the anterior lateral medulla and participates in the integration of posture and motion. It receives fibers from the ipsilateral red nucleus in the mesencephalon, and the efferent fibers from the oliva enter the contralateral dentate nucleus in the cerebellum. Then, cerebellorubral fibers from the dentate nucleus connect the contralateral red nucleus. Impairment of this pathway is considered to be the pathological basis of HOD [5].
A variety of underlying etiologies have been described, including vascular lesions, toxicity, trauma, surgery, vascular malformation and tumors [4]. HOD may occur several months or even years in some cases after the primary cause. Studies have reported that HOD is almost predominantly unilateral [6]. Bilateral HOD is rare and can be caused by a para-median pontine lesion that affects both the central tegmental tract and the superior cerebellar peduncle and leads to inferior olivary nucleus degeneration [7]. Wernekinck commissure syndrome is a typical but rare syndrome caused by a lesion in the Wernekinck commissure, characterized by bilateral cerebellar dysfunction, variable eye-movement disorders, and occasionally delayed palatal myoclonus [8]. Bilateral caudal paramedian midbrain infarction demonstrated the characteristic “heart appearance” on MRI and clinically demonstrated Wernekinck commissure syndrome was first reported in 2017 [9]. Delayed palatal myoclonus and hypertrophy olivary degeneration in the medulla oblongata were caused by primary lesions in the dento-rubro-olivary pathway. In our case, we present a unique case of HOD that was considered to be caused by a heart-shaped midbrain lesion. The patient was diagnosed with Wernekinck Commissure Syndrome resulting from a midbrain heart-shaped infarction 3 years ago. Symptoms of HOD appeared 2.5 years after the primary cause, and bilateral HOD was confirmed by MRI after admission.
The clinical signs of HOD include palatal myoclonus, ocular myoclonus, nystagmus, and holmes tremor, symptoms of cerebellar and brainstem dysfunction such as ataxia, dizziness, diplopia and blurred vision during or after the improvement of the primary disease. Among them, symptomatic palatal myoclonus is a hallmark symptom of HOD that often arises from lesions localizing in the Guillain–Mollaret triangle and loss of inhibitory inputs into the olivary nucleus. Symptomatic palatal myoclonus refers to rhythmic 1–4 Hz involuntary movements of the soft palate produced by irregular contractions of agonist muscles [10].
Histological changes in HOD include vacuolar degeneration, neuronal and astrocytic hypertrophy and gliosis. The disease course of HOD is a dynamic and evolving process that may take months to years to progress. The evolution of HOD may include olivary amiculum degeneration, neuronal olivary hypertrophy, olivary enlargement, degeneration of neurons and atrophy of the olivary nucleus [4]. A previous imaging study showed that visible changes on MRI correlate well with the described sequential histopathologic findings [11]. In the first 6 months of the ictus, increased T2 signal in the inferior olivary nucleus can be seen without hypertrophy. Then, hypertrophy of the inferior olivary nucleus appears and may last 3–4 years. Finally, olivary shrinkage becomes apparent, and increased T2 signals persist.
To date, there are no available specific therapies for patients with HOD. Previous studies have demonstrated that clonazepam, levodopa, dopaminergic agents, levetiracetam and deep brain stimulation may have varying degrees of efficacy [12]. HOD is considered to be a self-limiting disease, and the prognosis of HOD depends on the etiology. Unilateral HOD usually has a better and faster recovery of symptoms than bilateral HOD [7]. In our case, the main symptom that has an adverse impact on quality of life is gait instability; therefore, adamantanamine was administered for treatment. However, adamantanamine treatment was stopped due to inefficacy.
In conclusion, bilateral HOD is a rare degeneration that is mainly secondary to diseases affecting the Guillain–Mollaret triangle. In clinical practice, the diagnosis of HOD is not always recognized and may be wrongly mistaken for a second stroke or other pathology [13]. Increased awareness of patients at risk and pathophysiological mechanisms are essential for clinical surveillance and disease management. Our case suggests that patients with a history of midbrain injury, especially Wernekinck commissure, should be alert to the possibility of delayed bilateral HOD when new symptoms occur or original symptoms are aggravated.