Most brainstem hemorrhages occurring in the pons and midbrain, and hemorrhages restricted to the medulla oblongata have received little attention to date. Herein, we describe the clinical characteristics and prognosis of 11 patients (four men, age range of 11 patients: 20–65 years, mean age=44) with medullary hemorrhage recruited consecutively from Seoul National University Bundang Hospital from July 2004–January 2016 (Figure 1).
The most frequent symptoms in these patients included vertigo (n=10), headache (n=6), diplopia (n=3), and limb weakness (n=1). Table 1 shows the clinical features and prognosis of patients. More than half of patients (6/11, 55%) experienced minor transient or persistent neurologic symptoms, including vertigo (n=3), sensory changes in the face (n=2) or extremities (n=2), dysarthria (n=1), tinnitus (n=1), and dysphagia (n=1), within one month of presentation. In contrast, five patients (5/11, 46%) required advanced airway management in the intensive care unit. Hematoma expansion was observed in four patients during follow-up imaging (4/9, 44%). Patients usually had minor functional deficits three months after presentation (modified Rankin Scale ≤2 and/or Bathel Index 90; n=8).
All patients showed spontaneous nystagmus without fixation (n=11; upbeat in eight, downbeat in one, and horizontal in two), which accompanied other neuro-otological findings (Table 2), including central positional nystagmus (7/9, 78%), gaze-evoked nystagmus (6/11, 55%), ocular lateropulsion (4/11, 36%), skew deviation (5/11, 45%), or abnormal head-impulse tests (3/11, 27%). The etiologies of the medullary hemorrhages were mostly cavernous malformation (n=9), hemorrhagic transformation following lateral medullary infarction (n=1, patient 5), or undetermined (n=1, patient 1).
In our patients, the presenting symptoms were mostly vertigo and headache. Furthermore, over half of the patients experienced prior minor neurologic symptoms, which is uncommon in pontine or midbrain hemorrhage [1-3]. In contrast, most patients with pontine hemorrhage present with mental changes (47%) or hemiparesis (41%) . Likewise, patients with midbrain hemorrhage frequently show mental changes (53%), and limb weakness (49%) . Thus, we assume that the characteristics of hemorrhage secondary to cavernous malformation are different from those due to hypertensive hemorrhages. Intermingled vascular spaces or sinusoids would be affected less by arterial pressure than regions irrigated by small arterioles, which are vulnerable to hypertension . Neurological impairments may worsen due to repeated seepage or oozing, or due to the toxic effects of hemosiderin deposits. Approximately half of our patients eventually showed a mental change that prompted mechanical ventilation. Therefore, close observation is essential in such patients.
Here, the cause of medullary hemorrhage was mostly cavernous malformation, which refers to abnormally enlarged vascular cavities without intervening brain parenchyma. Approximately 5% of cavernous malformations involving the brainstem reside in the medulla oblongata . Unlike those in the supratentorial area, the cavernous malformations involving the brainstem become symptomatic easily, and neurological progression can occur because of even a small amount of bleeding. Although about half of our patients experienced severe neurological deterioration that required mechanical ventilation, the overall outcome after three months was relatively favorable compared to pontine hemorrhage, in which patients mostly end up in a vegetative state or die, and independent living is rarely possible (18%) .
All patients presented with typical neurological findings, mostly resulting from the involvement of the neural structures in the medulla oblongata, including the medial lemniscus, spinothalamic tract, tract of the trigeminal nerve, inferior cerebellar peduncle, nucleus ambiguous, and hypoglossal nucleus [6,7]. We propose that the intercalatus nucleus and the nucleus of Roller, or the caudal cell groups of the paramedian tract may be the neural substrates for the upbeat or downbeat nystagmus observed here. In contrast, the dissociated torsional-upbeat nystagmus observed in two patients might be explained by unilateral or bilateral damage to the vestibulo-ocular reflex pathway ascending in the medial longitudinal fasciculus . The direction-changing gaze-evoked nystagmus indicates damage to the vestibular nucleus or nucleus prepositus hypoglossi . Disruption of the nodulouvular projections onto the vestibular nuclei may cause apogeotropic or geotropic positional nystagmus . Ocular lateropulsion has been ascribed to damage of the olivocerebellar fibers, before or after decussation in the medulla, projecting to the cerebellar Purkinje cells, which in turn project to the paramedian pontine reticular formation .
Neuro-otologic evaluation may prove valuable for detecting medullary hemorrhage. Given the rare incidence of spontaneous hemorrhages in the medulla, underlying vascular malformations should be considered.
This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI10C2020).
Pt, patient; hGEN, horizontal gaze-evoked nystagmus; HIT, head-impulse test; HSN, head-shaking nystagmus; F, female; R, right; U, up; OU, both eyes; L, left; M, male; D, downbeat; OD, right eye; OS, left eye; CCW, counter-clockwise (upper poles of the eyes beating to the left shoulder).
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