Oculo-palatal tremor following brainstem stroke with hypertrophic olivary degeneration

Dear Sir, A 54-year-old hypertensive right-handed gentleman suffered from a brainstem hemorrhagic stroke one year back. Computed tomography (CT) scan at the time of the index event revealed a hematoma in the dorsal pons [Figure 1a]. At presentation, his intracerebral hemorrhage (ICH) score was 2 and the modified Rankin score (mRS) was 5. Previous medical consultation notes showed that he had developed right-sided hemiplegia with left-sided gaze palsy at the time of admission. He was managed conservatively, yielding an mRS of 4 at discharge.Figure 1: (a) Axial T2 fluid attenuation inversion recovery (FLAIR) sequence on MRI shows hyperintensity with enlargement of the left inferior olive (arrow) (b) Corresponding T1 weighted axial sequence at the level of the medulla showing an isointense appearance of the left inferior olive (c) Coronal T2-weighted image shows hyperintense inferior olive on the right side, with a hypointense signal in the pons suggesting a residual blood product (d) Axial CT scan of the index event revealing hematoma in the dorsal ponsAfter approximately nine months, the patient presented with complaints of dysphagia, oscillopsia, and ataxia. He also developed a right-sided spastic hemiparesis. Sensory examination revealed loss of pain and temperature on the right half of his body, excluding the face. Inspection of the oral cavity revealed a rhythmic, involuntary, oscillatory movement of the soft palate and pterygopalatine arch, without a clicking sound. The left side of the palate showed a decreased elevation, accompanied by atrophy of the left side of the tongue. The tip of the tongue deviated to the left on voluntary protrusion. He experienced dysphagia to liquids and solids, necessitating nasogastric feeding. In addition, there was a pendular, vertical nystagmus with a torsional character beating toward the left ear. The patient also exhibited an ipsilateral “one and a half” syndrome (OAHS) [Video 1], characterized by a conjugate horizontal left-sided gaze palsy, accompanied by failure of adduction of the left eye and abduction nystagmus of the right eye. The conjugate gaze restriction persisted during saccades, pursuits, and oculocephalic maneuvers. Vertical gaze was preserved. The vertical ocular movements were synchronous with the palatal oscillations. Brain magnetic resonance imaging (MRI) revealed hypertrophied inferior olive (IO) on the left side of the medulla [Figure 1]. Treatment with gabapentin and clonazepam led to amelioration of abnormal palatal and ocular movements. A multidisciplinary approach was adopted, with a focus on physical rehabilitation, nursing care, and secondary stroke prevention. {"href":"Single Video Player","role":"media-player-id","content-type":"play-in-place","position":"float","orientation":"portrait","label":"Video 1","caption":"","object-id":[{"pub-id-type":"doi","id":""},{"pub-id-type":"other","content-type":"media-stream-id","id":"1_kvjnhbq8"},{"pub-id-type":"other","content-type":"media-source","id":"Kaltura"}]} Oculo-palatal tremor (OPT) is a rare hyperkinetic movement involving rhythmic oscillations of the soft palate occurring synchronously with pendular nystagmus.[1] It is believed to be a delayed complication of brainstem/cerebellar lesions causing deafferentation of the inferior olive from the dentato-rubro-olivary pathway or the Guillain–Mollaret triangle (GMT)[1,2] [Figure 2]. The GMT is formed by three structures,[2] namely the contralateral dentate nucleus (DN), ipsilateral red nucleus (RN), and ipsilateral inferior olivary nucleus (IO). The connections within the GMT are as follows: (1) the dentato-rubral pathway, connecting the DN to the opposite RN through the superior cerebellar peduncle (SCP), decussating at the midbrain; (2) the rubro-olivary pathway, descending from the RN to the ipsilateral IO through the paramedian dorsal pontine tegmentum; and (3) the olivary-dentate or olivary-cerebellar fibers, ascending through the inferior cerebellar peduncle (ICP), connecting the IO on one side to the DN on the other. Disruption of afferent connections to the inferior olive (i.e., dentate-rubral and/or rubro-olivary), and not the efferent pathways, is responsible for hypertrophic olivary degeneration (HOD).[2,3] Following such a lesion, the IO hypertrophies are caused by the development of soma-somatic gap junctions between adjacent neurons. This causes electrical coupling, fortified by disinhibition from deep cerebellar nuclei, thus generating strong, synchronized oscillations.[4] Frequent etiologies for HOD include stroke, tumors, trauma, post-surgery vascular malformations, and, rarely, multiple sclerosis.[5,6] The absence of the clicking sound, unremarkable neurological examination (apart from palatal tremors), and normal brain imaging differentiate the essential palatal tremors from the symptomatic variant.[7] The lower motor neuron signs in bulbar cranial nuclei (9th,10th, and 12th) in the present case can be attributed to the degenerative changes in the ipsilateral medulla revealed by imaging.Figure 2: Illustrative sketch of the Guillain–Mollaret triangle (GMT). Possible sites of injury are (1) dentate and/or SCP (yellow), (2) paramedian lesion involving SCP on one side and CTT on the other (green), and (3) dorsal pontine lesion involving CTT (brown)OAHS is an interesting ocular abnormality characterized by a combination of ipsilateral conjugate, horizontal gaze palsy (“one”), and ipsilateral internuclear ophthalmoplegia (“half”).[8] The cause of this OAHS is a solitary, unilateral lesion targeting the paramedian pontine reticular formation (PPRF) or the sixth cranial nerve (abducens) nucleus, leading to interruption of internuclear fibers of the ipsilateral median longitudinal fasciculus (MLF) after its decussation from its origin in the contralateral abducens nucleus. The former causes the conjugate gaze palsy, whereas the latter is responsible for the failure of adduction of the ipsilateral eye.[8,9] Common etiologies are usually demyelinating lesions (multiple sclerosis), brainstem infarcts, tumors, and arterio-venous malformations.[8] As discussed, the GMT is an intricate circuit prone to perturbations anywhere in its vicinity, vascular lesions (i.e., cavernous malformations and stroke) being the most common causing factor.[2] Aberrations in the circuitry develop over a period, ranging from months to several years, owing to neuroplasticity. The patient in focus, presented with hyperkinetic, synchronous, involuntary palatal and ocular movements after almost a year from the initial date of vascular insult. Radiological differentials of olivary hypertrophy include demyelination, tumors, metastasis, lymphomas, and, rarely, infections. However, the lack of contrast enhancement, visible olivary swelling, chronology of historical events, and imaging results favor a diagnosis of HOD. Pathologically, the progression of HOD is a dynamic process that evolves over months to years. Biopsy studies have documented the chronology of histological changes in the anatomy of the inferior olive.[10] The natural history is typically comprised of six stages: (1) absence of gross changes in the first 24 hours, (2) degeneration of the olivary amiculum occurring within 2 to 7 days or more, (3) onset of olivary hypertrophy at approximately 3 weeks, (4) the maximum period of olivary enlargement characterized by neuronal and astrocytic hypertrophy at approximately 8.5 months or more, (5) the stage of olivary pseudohypertrophy, with neuronal degeneration and astrocytic hypertrophy at 9.5 months or more, and (6) the stage of olivary atrophy approximately 3 to 4 years after the initial insult. These pathological stages are noted to correlate with radiological findings.[2] Regular follow-up of survivors of brainstem lesions is crucial considering involuntary, abnormal ocular and/or palatal movements are delayed complications. Palatal tremors can often be asymptomatic and may otherwise be undetected unless specifically searched for. Acknowledgement We would like to express our sincere gratitude to our colleagues and teachers for their guidance and unwavering support. We also express thanks to the patient and his relatives for their co-operation and faith. Author contribution Research project: Conception: Amlan Kusum Datta, Sudeshna Malakar Organization: Amlan Kusum Datta, Sudeshna Malakar, Adreesh Mukherjee Execution: Amlan Kusum Datta, Sudeshna Malakar Statistical analysis: Design: Amlan Kusum Datta, Sudeshna Malakar Execution: Amlan Kusum Datta, Sudeshna Malakar Review and Critique; Adreesh Mukherjee Manuscript preparation: Writing of the first draft: Amlan Kusum Datta Review and Critique: Sudeshna Malakar, Adreesh Mukherjee Ethical compliance statement Informed consent was obtained from individual participant involved in the study and all procedures were in accordance with institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No funding or grants were received for the completion of this study. This article does not include any studies involving animals performed by any of the authors. The authors declare that they have no conflicts of interest. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.