Continuing Education Activity

Foster Kennedy syndrome (FKS) is characterized by visual loss due to compressive optic atrophy in one eye and papilledema in the contralateral eye brought on by increased intracranial pressure. The underlying cause of this ophthalmologic condition is the presence of an intracranial space-occupying lesion that compresses the ipsilateral optic nerve, which gives rise to optic atrophy. The lesion can also cause increased intracranial pressure, thus explaining the papilledema in the fellow eye found in FKS. Meningiomas are the most common type of tumors found in the brain of patients with FKS. There are typically three types of FKS, based on whether or not the atrophy and papilledema are unilateral or bilateral. Type 1 is the most frequent presenting form with optic atrophy in the ipsilateral eye and papilledema in the contralateral eye. Pseudo-FKS has a similar clinical presentation of FKS; however, there is no underlying compressive pathology in pseudo-FKS. In some individuals, the onset of these acute ophthalmologic signs and symptoms can assist in the diagnosis of an underlying severe neurological disease; thus, proper differential diagnosis and thorough examination and testing are essential. This activity describes the evaluation and management of patients with Foster Kennedy syndrome and points to the role of the interprofessional team in managing patients with this condition.

Objectives:

• Describe the pathophysiology of patients with Foster Kennedy syndrome.
• Review the etiology of Foster Kennedy syndrome.
• Identify the common clinical presentation of Foster Kennedy syndrome, including clinical results and imaging findings associated with these patients.
• Explain the typical treatment considerations for patients with Foster Kennedy syndrome.

Introduction

Foster Kennedy syndrome (FKS) is based on neurological signs characterized by anosmia and vision loss (central scotoma), which may be unilateral or bilateral depending on the stage of the condition. It is defined by compressive optic damage (atrophy) in one eye and contralateral papilledema, resulting from increased intracranial pressure secondary to an intracranial space-occupying lesion.[1]

It is worth noting that the classic presentation of FKS is also found in pseudo-FKS; thus, it is of utmost importance that the attending clinician is astute in selecting and carrying out the proper examination techniques to provide an accurate diagnosis.

There are typically three types of FKS.[2] Type 1, the most frequent form,  presents with optic atrophy in the ipsilateral eye and papilledema in the contralateral eye. Type 2 is characterized by bilateral papilledema and unilateral optic atrophy.[3] Type 3 is defined by bilateral papilledema developing into bilateral optic atrophy. The three types of FKS are caused by different stages of metastasis of brain tumors.

Pseudo-FKS has the typical presentation of optic atrophy in one eye and papilledema in the contralateral eye, similar to type 1 FKS.[4] However, there is no underlying compressive pathology in pseudo-FKS.[5][6] Causes of pseudo-FKS include optic nerve compression by the gyrus rectus, diabetic papillopathy, and unilateral optic nerve hypoplasia.[7][8]

Meningiomas (See Figures of computerized tomography scans of frontal-temporal meningioma and frontal-sphenoidal meningioma) are space-occupying tumors originating in the central nervous system.[9] The term refers to specific disorders of the pia, dura, and arachnoid layers encapsulating the brain. They can either be cancerous or non-cancerous.[10] The common sites for occurrence include the sphenoid wing, olfactory groove, and frontal lobe.[11][12]

Meningiomas are the most common type of non-malignant tumors found in the brain.[13] Meningiomas are often insidious in progression, leading to subtle progressive changes that may go unnoticed as the condition progresses. They may initially herniate into the subarachnoid space and dural sinuses leading to intracranial hypertension. Meningiomas eventually compress on adjacents vessels and sections of the brain, causing an array of symptoms and eventual tissue atrophy.

Tumors of the pituitary gland have also been reported to cause FKS and are the second-highest cause of cerebral tumors.[14][15] This risk becomes exacerbated in patients who have undergone surgical resection for pituitary adenomas and radiotherapy as they may subsequently develop complications, including tentorial meningiomas.[16][17][18]

Etiology

Brain tumors account for about 12% of optic disc swelling.[19] The mass-causing lesion is usually an anterior cranial fossa meningioma. However, tumors in other parts of the brain like the frontal lobe, olfactory groove, sphenoid wing, and pituitary gland can also cause the condition (See Figures of computerized tomography scans of frontal-temporal meningioma and frontal-sphenoidal meningioma).[15][8]

Risk factors for meningiomas include hereditary factors, female hormones, and prior radiation exposure.[20] These tumors compress on the optic nerve on the ipsilateral side of the brain in which they are formed, causing progressive optic atrophy. As they grow larger, they may breach the cerebral falx and cross over to the contralateral side, causing a restricted flow of the cerebrospinal fluid and papilledema in that eye. Alternatively, a patient may present with complete optic atrophy in one eye and temporal hemianopsia in the other eye.[15]

Epidemiology

Studies have shown the age-adjusted incidence rate of central nervous system tumors to be 23.41 per 100,000 individuals.[13] The reported rates were slightly higher in females.[20] FKS has been reported in 1 to 2.5% of intracranial tumors.[21]

Pathophysiology

Foster Kennedy syndrome forms due to intracranial space-occupying lesions (ICSOL), especially those in the anterior cranial fossa. The presence of the ICSOL causes an increase in intracranial pressure and direct compression of the nerve, which results in ipsilateral optic atrophy due to the death of nerve fibers, considering that the nerve fiber swelling is usually not noticed in the limited fibers remaining after the damage.

The increased intracranial pressure causes the swelling of the optic disc of the contralateral eye, which still has enough nerve fibers that make swelling evident. The anosmia is a result of the ICSOL compressing the olfactory nerve.

History and Physical

When discussing signs and anamnesis with patients, it is important to note complaints of headaches, unilateral or bilateral reduction in vision, and anosmia in some cases (later stages of the condition). The clinician can expect to see an elevated optic disc (papilledema; detection of papilledema can be tricky at the early stages, especially in stage 1 papilledema, which may show a C-shaped halo with preservation of the temporal margin of the disc).

The later stages of the sign papilledema are more easily identifiable due to the elevation of the disc with obscured blood vessels. These more advanced stages of papilledema can be correlated with signs of a tumor in the forebrain, including emotional lability, difficulties in moving/uncoordinated movement, and a speech impediment. ICSOL of the forebrain can extend beyond the anterior cranial fossa and, as such, present with other associated tumors affecting other parts of the brain.

Evaluation

The initial evaluation of Foster Kennedy syndrome is usually via a funduscopy, preferably dilated. Ophthalmoscopy, slit-lamp biomicroscopy with an accessory lens or fundus imagery allows the examiner to visualize the back of the eye. Visualization of optic atrophy and damage to the retinal nerve fiber layer is enhanced with a red-free filter. Papilledema is best assessed by directly viewing the optic disc using a slit aperture during ophthalmoscope, which is a typical feature in FKS.[22]

Radiologic imaging may precede or follow ocular examination depending on the flow of patient care. Standard X-rays are not very useful in detecting brain tumors because the skull absorbs the radiation, thus preventing deeper tissue viewing.

Literature shows a positive correlation between raised intracranial pressure and increased intraocular pressure. Intraocular pressure can be measured by contact or non–contact tonometry.[23][24]

Computerized tomography (CT) scans use X-rays emitted through different body parts combined with a computer algorithm to generate scans of slices of the part of the body being imaged. The patient should be advised to minimize movement during the procedure for optimum image quality. Metals, reflective objects, and clothing should also be removed from the head before imaging. The patient usually lies prone on an electronic bed while the equipment takes multiple scans as it rotates around the body. An iodine-based contrast agent may be injected into the patient’s vein to give even better scan images.[25] 

It is important to ensure an appropriate kidney function testing is done to ensure the patient can eliminate the agent after administration.[26][27][28] A CT scan is contraindicated in pregnant individuals and requires skilled interpretation to make a proper diagnosis.[29] A CT scan tends to be fast and accurate in assisting in the differential diagnosis in patients with FKS.[30][31]

Magnetic resonance imaging (MRI) provides more enhanced images than a CT scan. In addition, it does use ionizing radiation and is therefore safer. MRI uses a magnetic field to disrupt the random arrangement of atoms in the body into a systematic arrangement.[32] The equipment then sends a radio wave that excites these atoms from their new position. When this radio wave is turned off, the atoms return to their initial position, giving off a radio signal in the process.[33] 

An embedded algorithm in the MRI equipment then converts these emitted signals into a two-dimensional image of the part of the body being observed.[34] Because of the absence of ionizing radiation, an MRI is the scan of choice used when monitoring the progression of a brain mass/tumor.[35][36]

This type of testing takes longer than CT scans, which can seldom be performed in emergency patients in most hospitals; thus needs to be booked and tends to come after the acquisition of CT scans in most patients with FKS.

Treatment / Management

The treatment modality for Foster Kennedy syndrome tumors include:

• Surgical resection
• Chemotherapy
• Radiotherapy
• Medical therapy

The management of FKS is usually by surgical resection, although chemotherapy and radiotherapy are also employed, especially in old geriatric patients who are more prone to mortality.[37][38]

Regarding medical therapy, the first line of action is to give systemic corticosteroids, although it is usually an asymptomatic treatment for the reduction of edema around the tumor and intracranial pressure.[39]

In older patients, it is preferable to go for a non-neurosurgical procedure such as stereotactic radiotherapy and radiosurgery. The use of hydroxyurea has been anecdotally found to be useful, especially for unresectable tumors and large residual tumors.[40]

Differential Diagnosis

The differential diagnosis of Foster Kennedy syndrome include:

• Frontal lobe parenchyma tumors
• Meningioma (e.g., olfactory, frontal, sphenoid wing)
• Pseudo-FKS
• Non-arteritic anterior ischemic optic neuropathy (NAION)
• Optic nerve hypoplasia
• Optic neuritis
• Vitamin B12 deficiency

Tumors that affect the frontal lobe are included in the differential diagnosis of FKS, especially those affecting brain structure in the anterior cranial fossa. Tumors of the brain meninges, i.e., those involving the olfactory, frontal lobe, and sphenoid wing, need to be considered. These tumors can occur without ocular complications and would therefore not qualify as FKS.

Pseudo-FKS is the most common differential diagnosis of FKS; simplifying its definition, one can say pseudo-FKS is FKS without a tumor.[1] Pseudo-FKS can mimic FKS, but the clinical features and presentation are different. One fundamental difference is the absence of tumors, which means less emotional or intelligence lability.

NAION is the second highest cause of optic neuropathy. It is a condition of non-inflammatory ischemia of the 1mm region of the optic disc typically due to the reduction in blood flow through the posterior ciliary artery, which supplies the optic nerve head (anterior part of the optic nerve). It has been suggested to be caused by embolism. It can also be caused by a nocturnal drop in perfusion pressure.[41]

Optic nerve hypoplasia is a congenital condition in which the optic nerve does not develop fully, thus giving the classic small and pale appearance of the optic nerve. There are cases where optic nerve hypoplasia is seen together with NAION.[8] The causes have not been clearly understood, but there have been correlational studies showing the relationship between optic nerve hypoplasia and fetal alcohol syndrome in addition to maternal intake of quinine, phenytoin, and lysergic acid diethylamide.

Optic neuritis is the inflammation of the optic nerve and is called optic papillitis when it involves the optic nerve head. It is called neuro-retinitis when it involves the optic nerve head and the macula. It is termed retrobulbar neuritis when it involves the posterior part of the nerve.[42] 

Papilledema is a sign of a pathologic condition in the eye presenting as an elevation of the optic nerve head. It results from a sustained increase in the intracranial pressure with varying degrees of blurred optic disc margin and reduction.

Vitamin B12 deficiency can also result in progressive optic neuropathy, masquerading as FKS. This condition is, however, reversible with appropriate supplements.[43]

Surgical Oncology

The decision to proceed to surgery for Foster Kennedy syndrome depends on a risk-benefit analysis as recommended by the consulting physicians. Brain surgery is a multi-disciplinary decision and procedure. As with all tumors, complete removal of the cancer is recommended in the event of surgical intervention. Tissue samples should be sent for a histopathological examination for a better understanding and staging of the lesion. Surgery can be followed by adjuvant chemotherapy.[38][40]

Radiation Oncology

Radiotherapy is recommended as an adjunct treatment to surgery and for people with recurrent tumors.[44] While some authors recommend radiotherapy immediately, others advise using radiotherapy later if the lesion shows signs of progression and/or recurrence.[45][46]

Prognosis

The prognosis of Foster Kennedy syndrome is determined mainly by the location, size, and stage of the causative ICSOL.

Complications

Complications from Foster Kennedy syndrome can either be ocular or systemic. Ocular complications of FKS include disc edema, relative afferent pupillary defects, restriction in ocular movements, decreased visual acuity, papilledema, and optic atrophy.[21]

Systemic complications include anosmia and all other symptoms that may arise from a tumor compressing specific brain areas.

Deterrence and Patient Education

Foster Kennedy syndrome can sometimes be the first signs and symptoms that initiate further investigations and examinations, which provide the diagnosis of a brain tumor. It is important to inform the patient of the necessity of a multidisciplinary approach to correctly manage the disease to address issues related to the quality of life, treatment, and prognosis.

Enhancing Healthcare Team Outcomes

Eye care providers must be able to detect conditions like optic atrophy and papilledema, as this may be the first opportunity to diagnose a much more severe disease. Clinicians who suspect FKS in a patient must immediately send for detailed brain scans to localize the location of the ICSOL.

The results of these scans can direct neurosurgeons on the best route of action. While clinicians tend to prefer surgery as first-line treatment, chemotherapy and radiotherapy have also shown promising results in some patients. As with all tumors, the risk of metastasis and multiple organ involvement is always possible. FKS patients must be appropriately counseled on management, treatment options, quality of life, the likely prognosis, risks of metastasis, and fatality of the disease.

Interprofessional teamwork involves clinicians and nursing staff, and when medical management is part of the picture, pharmacists are important in optimizing care for patients with FKS. ALl te4am members must be diligent in documenting their findings, monitoring patient progress, contributing from their area of expertise, and keeping all other interprofessional team members informed of any status changes so corrective action can be implemented if necessary. This interprofessional approach will yield the best possible outcomes. [Level 5]