A 23-year-old man presented to the ED of a level III trauma center with a 2-hour history of acute diffuse throbbing headache, which he described as “the worst headache I've ever had.” He said the headache woke him from sleep, and was accompanied by nausea, vomiting, and photophobia.
The patient denied any loss of consciousness, fever, neck pain or stiffness, facial numbness, slurred speech, focal numbness, tingling, or other muscle weaknesses. He was unable to identify any alleviating factors, including remaining still and keeping his eyes closed. He also denied any aggravating factors such as head movement or change of position including supine. Before this ED presentation, the patient reported that he was otherwise healthy without any past medical history of headache or visual disturbances, known recent or distant head trauma, prior history of traumatic brain injury, or surgical history. His social history was noncontributory and he denied using tobacco, alcohol, or recreational drugs. He denied any current use of medications or dietary supplements.
The patient appeared mildly anxious and in moderate distress, but was otherwise well appearing. His vital signs were BP, 129/69 mm Hg; heart rate, 79 beats/minute; respirations, 18; oral temperature, 97.6° F (36.4° C); and SpO2, 100% on room air. Examination of the head, eyes, ears, nose, and throat yielded no concerns. Specifically, he had no retinal hemorrhage or papilledema, and no nuchal rigidity. The patient had normal mental status and his neurologic examination, including cranial nerve examination, revealed no deficits. His performance of finger to nose, heel to shin, and pronator drift were within normal limits. The patient demonstrated intact muscular strength and sensation, normal balance and gait, and his deep tendon reflexes were preserved. The skin examination was free of overt signs of trauma, infection, rash, or vesicles. Examinations of heart, lungs, abdomen, and musculoskeletal system were unremarkable.
- primary headache (tension, migraine, or cluster headache)
- subarachnoid hemorrhage
- intraventricular tumor
- cerebral venous sinus thrombosis
The patient's history and symptoms were less suggestive of cluster headache. Though cerebral venous sinus thrombosis could present with acute headache, it was less likely due to the patient's lack of risk factors. The patient denied any history of recurrent headaches, blood clots, nephrotic syndrome, recent head surgery, or known family history of neurologic disease. Peripheral access was obtained and IV hydromorphone 1 mg and ondansetron 8 mg were given for pain and nausea, respectively.
Given the severity of patient's complaint with acute atraumatic onset, an order was placed for brain CT imaging without contrast. This imaging revealed a 4.1 x 2.4 cm heterogeneous mass attached to the wall of the left lateral ventricle and the corpus callosum. The location of this mass obstructed the foramen of Monro, causing significant rightward shift of the septum pellucidum and hydrocephalus (Figure 1). MRI was recommended by the radiologist for greater enhancement. Due to the findings on CT, the potential for severe complication, and lack of neurosurgical services, transfer to a tertiary care hospital was arranged after discussion with the neurosurgeon. Before transferring the patient by ground ambulance to the tertiary care hospital 45 minutes away, the neurosurgical consultant advised concern for furthering mass effect and acute seizure onset, so the patient was intubated and given 1 g mannitol and 1 g phenytoin for seizure prophylaxis.
At the tertiary care hospital, the patient underwent emergent craniotomy, complete tumor resection, and ventriculostomy with external ventricular drainage (EVD) placement under general anesthesia. After regaining consciousness, he was admitted to the neurology ICU. Subsequent histologic analysis identified the mass as a central neurocytoma.
In the ensuing days, the patient continued to be stable and alert, although he remained in bed. During the third week of his hospital stay, he had several generalized seizures (30 to 60 seconds in duration) due to brain edema. He was treated with multiple rounds of IV lorazepam 2 mg, levetiracetam 1 g, valproic acid 300 mg, and mannitol 200 mg every 6 hours. His condition continued to worsen and he became unresponsive, febrile, and hypotensive with a BP of 90/20 mm Hg. He was reintubated; placed on mechanical ventilation; and given IV antibiotics, norepinephrine, and dopamine. Obstructed and nonfunctioning EVDs were thought to be the cause. The EVDs were replaced but the patient never regained consciousness. Three weeks after he first presented to the ED, the patient went into cardiac arrest and died.
Headache is a common condition seen in the ED. Although the vast majority of headaches are isolated and benign (often defined as a “primary headache”), clinicians must consider multiple life-threatening secondary causes. A sudden onset of severe headache reaching maximal intensity within minutes may suggest subarachnoid hemorrhage, and a headache with associated fever, neck stiffness, and/or immunosuppressive conditions such as HIV may point to meningitis or brain abscess.1 Headache associated with brain tumor is nonspecific and varies with tumor location and size—described by the International Headache Society as progressive, worse in the morning, and aggravated by coughing or bending forward.2 These signs and symptoms should prompt further evaluation, including imaging. In this case, the patient presented with a sudden onset of severe headache that woke him from sleep and was associated with nausea, vomiting, and photophobia, concerning for possible intracranial hemorrhage. Imaging evaluation revealed a central neurocytoma causing an acute obstruction of cerebrospinal fluid (CSF) flow, leading to significant hydrocephalus.
Central neurocytoma, a tumor of the intraventricular region, has an incidence of less than 0.5% of all primary tumors of the central nervous system.3-5 Owing to this rarity, literature on the topic is scarce, limited primarily to international case reports and clinical reviews from international neurology sources. As a result, most healthcare providers likely have little knowledge of this condition, although they are most likely to encounter it incidentally when it first presents. Although most authors generally consider central neurocytomas as benign, increasing incidence of malignant variants and local recurrence has been reported.3,6,7
Central neurocytomas were first reported in 1982 by Hassoun and colleagues, who described it as a “multicystic and calcified tumor with a broad-based attachment to the septum pellucidum or ventricular wall at the foramen of Monro.”8,9 Some have theorized that central neurocytoma develops from neuronal cells, neuronal progenitor cells, neuronal stem cells, and multipotent precursor cells.5,10,11 A well-differentiated tumor, central neurocytoma typically is seen in young adults (mean age at the time of initial presentation is 29 years), although case reports have shown an age range at diagnosis from 8 days to 67 years.3-5,9 Literature appears to demonstrate greater frequency in Korean, Japanese, and Indian populations, but this is primarily based on case reporting.4,12 Most central neurocytomas are found in the lateral ventricles, although some are located in the third ventricles and the foramen of Monro (Figure 2). In a study of 63 patients with confirmed central neurocytoma, 47.6% of the cases involved the left lateral ventricle, 39.7% involved the right lateral ventricle, and 12.7% involved both lateral ventricles.13 Kaur and colleagues noted that 39% of tumors extended into the third ventricle and 54% into the foramen of Monro.7 Location can play an important role in patient presentation because once it is large enough, a central neurocytoma can cause either primary mass effect symptoms in that area or secondary symptoms due to CSF drainage obstruction.
Most literature indicates that central neurocytomas usually follow a slow clinical course over several months to years; this is reflected by a World Health Organization classification as a grade II tumor, indicating only some potential for aggressive behavior.9,14 The original case reports of two patients with central neurocytomas illustrate timelines from first presentation to discovery of 1 and 3 years, with symptoms of progressive loss of memory and apathy, respectively.8 Given its slow growth, it is not surprising that patients commonly present with an insidious onset of vague symptoms such as headache, nausea, vomiting, and visual disturbance.3 However, acute obstruction of CSF flow also can lead to a sudden and severe onset of headache, as demonstrated by the patient in this case.4
In a primary care setting, central neurocytoma is likely to be an unexpected finding on head imaging following headache complaints. It typically appears as a heterogeneous, isointense, or hyperintense intraventricular mass on CT and on T2-weighted images on MRI.9 Central neurocytoma shares similar imaging characteristics with other intraventricular tumors, most notably ependymomas, meningiomas, and oligodendrogliomas, and may be difficult to differentiate from these more aggressive tumors.5,13 Therefore, definitive diagnosis requires histologic study.
Although there is no shared consensus to guide ideal management of central neurocytoma, most authors favor complete surgical resection as the mainstay for primary tumors.5-7 Tumor resection eliminates mass effect and obstruction, and can reestablish normal CSF flow. Successful tumor resection has favorable long-term survival rates of 93.3% and 85.4% at 5 and 10 years, respectively.3 However, complete resection may not be feasible in all patients, primarily due to location depth, proximity to critical structures, and/or adhesions. Previous studies found complete resection was possible in only 32% to 54% of cases.3,5 For patients who cannot undergo surgical resection, have incomplete resection, or have recurring lesions, radiotherapy such as fractionated conventional radiotherapy and stereotactic radiosurgery is an option.4,5 Chemotherapy may also be beneficial in patients with recurrent central neurocytoma that cannot be resected or for patients who have failed radiotherapy.4,5
Central neurocytoma is a benign intraventricular tumor affecting young adults. On very rare occasions, it can cause severe headache secondary to acute obstruction of CSF flow. Suspect central neurocytoma when an intraventricular mass is noted on head CT or MRI; definitive diagnosis requires histological study because of gross similarities with other intraventricular brain tumors on imaging. Complete tumor resection provides excellent prognosis, but for patients who are not able to undergo complete tumor resection, radiotherapy and chemotherapy are options.
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