Olfactory Groove Meningiomas: Psychiatric Symptoms Foster Misdiagnosis
Olfactory groove meningiomas are benign tumors that grow along the midline floor of the anterior cranial fossa. Rarely, they can undergo malignant transformation with metastasis. Although relatively uncommon, they are among the largest tumors discovered intracranially. Delayed diagnosis is the rule rather than the exception. Despite advances in imaging and therapeutic measures, the average size of these tumors at the time of surgical resection has not changed over the past few decades. The authors discuss common clinical hallmarks, the anatomic basis for the psychiatric and neurologic presentations, radiologic findings, treatment options, and outcomes, with an emphasis on neurologic clues that can lead to early diagnosis.
Despite significant advances in neuroimaging techniques over the past 2 decades, most olfactory groove meningiomas are still very large (>4 cm) at the time of diagnosis.1,2 Most often, patients present with anosmia and psychiatric symptoms, such as apathy, depression, or psychomotor retardation, whereas urinary incontinence and gait disturbances are late findings. Therefore, patients often receive psychiatric treatment, sometimes for prolonged periods of time, before neurologic deterioration prompts imaging of the brain. A high index of suspicion is key to accurate and early diagnosis.
A previously healthy and independent 78-year-old woman was admitted to the psychiatric ward by family members. Her complaints included weakness, depressed mood, and new-onset urinary incontinence. She denied any constitutional symptoms, recent illness, or psychiatric history. Physical and neurologic evaluations were remarkable for a flat affect, psychomotor retardation, and urinary incontinence. She was diagnosed with a major depressive episode, and inpatient medical treatment was started. Despite aggressive therapy involving several medications, she continued to deteriorate over the next few weeks and developed visual and auditory hallucinations. Magnetic resonance imaging (MRI) scans of the brain revealed a large, midline extradural enhancing mass effacing the frontal lobes superiorly, with significant vasogenic edema (Figure 1). An olfactory groove meningioma was suspected.
The patient was then taken to the operating room, where a bifrontal craniotomy was performed. After interruption of the blood supply, the tumor was debulked and removed (Figure 2). Pathologic examination of the tissue confirmed the diagnosis of meningioma.
The recovery period was uneventful. The patient?s mental status slowly returned to normal, and the hallucinations and depressed mood resolved. She returned to her previous level of daily-living functioning. Her incontinence, however, persisted.
Meningiomas arise from arachnoid cap cells, which are specialized cells in the arachnoid granulations. They are typically benign, slow-growing tumors that have on rare occasion been known to undergo malignant transformation with metastasis. Meningiomas are most frequently (40%) found on the convexities of the cerebral hemispheres.3 They are the most common nonglial-based intracranial neoplasms, representing 20% of all intracranial tumors.3
Olfactory groove meningiomas comprise about 14% of all basal meningiomas.4 The peak incidence is between ages 40 and 60 years, and twice as many women as men are affected.1
The neurologic deterioration associated with meningiomas is the result of 2 different mechanisms. First, as the tumor enlarges, it exerts a mass effect on the immediately adjacent neuronal fibers. Over time this pressure leads to demyelination and necrosis of the fibers, causing irreversible damage. The second mechanism is the presence of edema in the brain tissue surrounding the meningioma. The nature of this edema is vasogenic. It begins with increased vascular permeability and movement of fluid out of the vascular compartment into the extracellular space because of disruption of the blood-brain barrier.
The etiology of meningiomas is still unclear but is thought to be multifactorial. A genetic predisposition has been demonstrated in patients with neurofibromatosis type 2 who have lost part of chromosome 22.5 These individuals may develop multiple meningiomas and neurofibromas.5 Sex hormones, specifically estrogen and progesterone, have been implicated in the pathogenesis of meningiomas, as demonstrated by the female predominance in this disease. Estrogen and progesterone receptors are found in up to 50% and 90% of tumors, respectively.6
Cranial radiation is a definite risk factor for developing meningiomas. Patients with a history of cranial radiation therapy have a 4 times greater rate of meningioma formation compared with the general population.7
Edema is a significant cause of neurologic decline. This phenomenon is reversible with surgical resection of the tumor, after which the edema resolves over time.
The clinical presentation of our case exemplifies some of the neurologic hallmarks of an olfactory groove meningioma. The anatomic location of this tumor and its growth pattern underlie the clinical picture. Olfactory groove meningiomas arise from the region between the crista galli and the planum sphenoidale (Figure 3). As a result, the olfactory tracts are displaced laterally and are compressed, leading to anosmia. The base of the frontal lobe is displaced superiorly and posteriorly. In larger tumors, encroachment of the optic nerves can lead to papilledema and loss of visual acuity.1
Correct diagnosis is often delayed because of longstanding psychiatric symptoms that lead to misdiagnosis and mistreatment. One study found that the average duration of symptoms before diagnosis was 39 months.8 One of the most common symptoms seen in patients with olfactory groove meningiomas is depression.9 As in our patient?s case, many patients are prescribed antidepressant medications. Sometimes there is a temporary improvement of symptoms, presumably secondary to the transient effects of antidepressant therapy, but as the tumor grows and the edema worsens, there is always recurrence of symptoms and further deterioration.10
The key to preventing delayed diagnosis of olfactory groove meningiomas is a thorough and meticulous physical and neurologic evaluation. The following findings should raise the index of suspicion of olfactory groove meningiomas when considering the diagnosis of depression in a patient:
? Lack of any precipitating factor before the onset of depression
? No personal or family history of psychiatric disorders
? Presence of ?hard? neurologic findings evident by the examination, such as hemiparesis, incontinence, or papilledema.
Any such accompanying finding should alert the physician to the need for further investigation of the underlying pathology beyond depression. Some authors advocate neuroimaging of the brain in any patient aged 40 years or older who experiences mental, cognitive, or emotional changes, has specific neurobehavioral or neurologic findings, or has a poorer-than-expected response to psychopharmacotherapy.11
Anosmia is often the first clinical symptom. The olfactory tract fibers are directly affected by the meningioma, since they emerge from the cribriform plate at the base of the anterior cranial fossa. Patients, how?ever, may not be aware of anosmia because of the gradual decline in olfactory function, or frequently only one side of the nose is affected, and many elderly persons already have a diminished sense of smell.12
As the tumor continues to grow in size and exert pressure on both frontal lobes, depression, apathy, psychomotor retardation, and other depressive (negative) symptoms begin to appear, which can be subtle and can develop over a long period of time.13 This may at first seem paradoxical. Damage to the base of the frontal lobe, with which the tumor is intimately involved, classically has been shown to cause manic (positive) symptoms, such as mania, euphoria, or disinhibition. In contrast, depression and apathy (negative symptoms) have been linked to damage to the dorsal and lateral aspect of the frontal lobe. This paradox may be explained by noting that fibers arising from the dorsolateral convexities of the frontal lobe travel a longer distance than fibers arising at the base of the frontal lobe, which makes them more susceptible to demyelination and stretch damage caused by a mass effect or edema.
Urinary incontinence and gait ataxia are usually late symptoms.3 They also rarely recover after removal of the tumor, as in this case, because the cortical neurons controlling gait and micturition arise at the superomedial aspects of the cerebral hemispheres and travel up and around the lateral ventricles before making their way caudally into the internal capsule to reach their target destination. These neurons are indeed the longest tract fibers of the central nervous system. As such, a mass lesion is likely to stretch these elongated fibers.3 This mechanism is the same reason patients with normal-pressure hydrocephalus with enlarged lateral ventricles suffer from incontinence and gait ataxia.
Once a lesion is clinically suspected, diagnostic imaging is indicated. A pre- and postcontrast computed tomography (CT) scan of the brain is the first imaging study. Meningiomas appear extradurally, displacing the brain parenchyma without invasion. Most meningiomas enhance homogeneously with contrast. Some may be calcified, and others may have necrotic centers.14 Once the diagnosis of a lesion is made, an MRI scan of the brain can further elucidate the anatomy of the adjacent structures and more accurately evaluate the extent of the vasogenic edema. Often, magnetic resonance angiography is performed along with MRI to determine the location of the major cerebral vessels in relation to the lesion to aid in surgical planning.15
Surgical resection is the treatment of choice for most olfactory groove meningiomas.1 The exception is small lesions that are discovered incidentally by imaging in asymptomatic individuals. If the patient is clinically asymptomatic, and neurologic examination is normal, the lesion can be observed clinically by a neurosurgeon with regular-interval imaging to monitor tumor growth.3
The mainstay of medical management during the perioperative period is the administration of systemic corticosteroids. The purpose is to reduce the inflammatory response and the release of the vasoactive substances responsible for the disruption of the blood-brain barrier, thereby lessening the vasogenic edema surrounding the lesion. Steroids are usually continued well into the postoperative period and then are slowly tapered over weeks to months.
A bifrontal craniotomy is the preferred surgical approach. Using this technique, the bony skull covering the anterior frontal lobes is removed and the dural layer opened. Through an interhemispheric approach, the tumor, adjacent brain parenchyma, and the vasculature are visualized. The blood supply to the tumor is identified and detached. The tumor is removed by debulking along with the affected piece of underlying dura and bone. The dural layer is then closed using an allograft substitute, and the bone flap is replaced.5 Radiation therapy is generally reserved for recurrences that are refractory to surgical resection.
Recovery is typically slow, but as the edema in the frontal lobes subsides, the patient?s clinical status improves. It is only at this time that any residual permanent neurologic deficit can be assessed.
Morbidity and mortality associated with operative treatment of olfactory groove meningiomas have improved greatly over the past 3 decades. A 15% mortality rate reported about 20 years ago16 has decreased to nearly 0% as a result of current microsurgical techniques and advances in perioperative care.2 Most postoperative morbidities are secondary to the sedentary lifestyles characteristic to patients with this condition. As a group, such patients are less active than the general population, predominantly because of the long-term hypoactivity of the frontal lobe. Although this hypoactivity improves in nearly all patients over the course of weeks to months, immediate postoperative complications, such as bronchopneumonia, pulmonary embolus, or myocardial infarction, are seen in as many as 30% of the patients.2,17 Recent publications further support the excellent long-term prognosis in treated patients. Recurrence rates are generally less than 10% in patients followed up to 8 years.2,18 Recurrence has been attributed to the incomplete removal of the involved bone.2,18 The risk of recurrence can be minimized with extensive resection of all suspicious underlying bone.1,18
Olfactory groove meningiomas, despite being slow growing and relatively uncommon, are among the largest tumors found intracranially. Advances in diagnostic and therapeutic measures notwithstanding, these tumors continue to grow and achieve astonishing sizes before they are discovered. This is because the tumor is located in a relatively ?silent? area of the brain, which allows the mass to continue to grow slowly before neurologic decline is evident. The key to early diagnosis, treatment, and improved outcome is an acute awareness of the condition, followed by the use of diagnostic imaging when appropriate. Patients with isolated and unexplained anosmia or depression, particularly the elderly, should be thoroughly evaluated, and careful attention should be paid to other neurologic findings.
1. Which of these statements about olfactory groove meningiomas is NOT true?
A. They are usually benign tumors
B. Peak incidence is between ages 40 and 60 years
C. There is a female preponderance among patients
D. They typically affect the temporal lobe
2. All these factors have been implicated in the etiology of meningiomas, except:
B. Cranial radiation
3. Any of these conditions can be the first symptom of olfactory groove meningiomas, except:
D. Urinary incontinence
4. Which of these functions is least likely to recover after the tumor is removed?
A. Urinary incontinence
B. Loss of visual acuity
D. Mental disorientation
5. Which of the following therapies would be the most appropriate perisurgical management of olfactory groove meningiomas?
D. Radiation therapy
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