The Guillain-Mollaret triangle, a pathway involved in regulating precise voluntary motor movements, is defined by three major anatomical structures: the contralateral dentate nucleus (DN), the inferior olivary nucleus (ION), and the ipsilateral red nucleus (RN), interconnected through three highly specialized neural pathways; 1) dentatorubral tract (dentato-rubral pathway) arising from the DN, traveling through the superior cerebellar peduncle (SCP) and decussating within the midbrain to enter the contralateral RN, 2) the ipsilateral central tegmental tract (CTT) (rubro-olivary pathway), which is located in the dorsal paramedian pontine region, descending from the RN to the original ION, and 3) the olivarydentate tract (olivo-cerebellar pathway), arising from the hilum of the ION and crossing the midline superiorly through the inferior cerebellar peduncle (ICP) to reach back to the contralateral DN (Figure 1) [1-3].

In this system, the afferent pathway to the ION begins in the contralateral DN of the cerebellum. Fibers from the DN cross the midline, enter, and synapse in the ipsilateral RN. From the RN, the pathway continues downward to reach the ION. This disynaptic pathway operates alongside a parallel monosynaptic route that bypasses the RN. Efferent fibers from the ION cross the midline to return to the contralateral DN, completing the loop [1].

Α disruption in the afferent pathways leading to the ION results in transneuronal degeneration and HOD. Its anatomical pathology involves an increased volume due to cytoplasmic vacuolar degeneration and a rise in the number of astrocytes. It is generally considered unlikely that a lesion affecting the efferent pathway between the ION and the contralateral DN would typically cause HOD [1, 2]. 

HOD arises from damage to the GMT, typically following brainstem or cerebellar lesions, with predominant vascular causes —including cavernous malformations, ischemia, and hemorrhages. Other causes include infarction, toxicity, trauma, surgery, and tumors. Less common causes are infectious diseases, including multiple brainstem abscesses generated by Listeria monocytogenes, Listerial Rhombencephalitis, and toxoplasmosis [4]. In sporadic cases, HOD has been reported to be idiopathic and secondary to Wilson's disease [2]. 

HOD is classified into three patterns based on the lesion's location: ipsilateral, contralateral, and bilateral (Figure 2) [1]. 

The cornerstone of diagnosis resides in recognizing the characteristic MRI findings, specifically the non-enhancing T2-hyperintense enlargement of the ION. Lack of gadolinium enhancement, a lesion in the contralateral cerebellum or ipsilateral brainstem, and clinical symptoms such as palatal tremor or ocular myoclonus provide strong evidence for diagnosing HOD [3, 5, 6].

Palatal tremor presents in two forms: an "essential" variant, which occurs without an identifiable structural cause, and a "symptomatic" variant (palatal myoclonus), which arises secondary to brainstem or cerebellar pathology. The latter is characterized by rhythmic and stereotyped palatal contractions at a frequency of 1–3 Hz, typically emerging within 10–11 months following an injury to the GMT [7]. Further clinical manifestations of HOD include nystagmus, dentatorubral tremor, and simultaneous contractions of the cervical muscles and diaphragm [1].

Pathologically, the changes of HOD include vacuolar degeneration, neuronal and astrocytic hypertrophy, and gliosis. The natural expected temporal evolution of HOD is divided into six stages [1, 2, 8, 9]:

1. first 24 h:  no noticeable changes 
2. 2–7 days or more: degeneration of the olivary amiculum (white matter capsule making up the olive periphery) 
3. 3 weeks: neuronal olivary hypertrophy 
4. after 8.5 months approximately: maximal olivary enlargement secondary to the hypertrophy both of the neurons and of the astrocytes
5. 9.5 months or later: pseudo-hypertrophy in which the neurons degenerate, but the large emistocytic astrocytes prevail  
6. 3–4 years after the lesion: atrophy of the olivary nucleus