Foix-Alajouanine Syndrome

Foix-Alajouanine syndrome is an arteriovenous (AV) malformation of the spinal cord predominantly affecting the lower thoracic and/or lumbosacral levels; cervical cord involvement is rare. Findings include necrosis of the affected cord regions. Grey matter (as compared with white matter) structures are more severely involved. (See Etiology.)

Masses of enlarged, tortuous, thick-walled subarachnoid veins are observed overlying the surface of the cord (primarily on the posterior aspect). Smaller blood vessels with thickened fibrotic walls also are present within the affected spinal cord segments (see the image below). (See Workup.)

Gross photograph of the dorsal surface of the spinal cord showing dilated and tortuous vessels.

Foix and Alajouanine first described the syndrome in 2 young men (aged 29 y and 27 y), in 1926.[3] Historically eponymic, the syndrome now has many other names in the literature, including angiodysgenetic necrotizing myelopathy, subacute necrotizing myelopathy, and venous congestive myelopathy.[4]

The etiology of Foix-Alajouanine syndrome is not well understood. Most patients have an AV fistula in the lower thoracic dura. One etiologic hypothesis is that the higher arterial pressure within the dura is transmitted to the spinal venous plexus via the intradural venous system, compromising perfusion and leading to infarction of the spinal cord parenchyma. Arterial blood originating from the dural fistula enters the venous system, increasing pressure and impairing normal drainage from the cord parenchyma.[4]

Thrombosis may occur, but not until late in the course of the disease. Venous stasis, not thrombosis, may be the primary cause of infarction. The preferential involvement of the distal cord is presumably due to orthostasis.

The onset in middle age suggests that the syndrome is acquired, in contrast to other vascular malformations, which are presumed to be congenital abnormalities, although the specificity for the spinal cord is not easily explained.

The enlarged, abnormal veins are associated with dural AV shunts or fistulas, usually intradurally, but rarely extradurally.[1] These AV shunts are associated with reflux of arterial blood into the venous drainage of the cord. This leads to congestion of venous outflow and results in increased venous pressure in the affected regions of the spinal cord, often leading to ischemic injury. (See Etiology and Treatment.)[2, 5]

Frequency

Foix-Alajouanine syndrome is a rare entity. No specific statistics are available with regard to its frequency in the United States, but the condition is likely underdiagnosed.A retrospective study from 2001 in Germany estimated a prevalence of 5-10 cases per one million people in the general population, though this disease is probably underdiagnosed.[12]

Mortality/morbidity

Outcomes after diagnosis and treatment depend on factors such as the duration of symptoms, the pre-treatment disability, and the success of the procedure to close the fistula. Symptoms that generally improve after treatment are gait difficulties and muscle strength. Micturition, pain, and muscle spasms are symptoms that often do not respond as well.[5]

Demographics

No data is currently available indicating if Foix-Alajouanine syndrome is more prevalent in specific ethnic/racial groups.

The male to female ratio for Foix-Alajouanine syndrome is approximately 5:1.[5]

Foix-Alajouanine syndrome usually occurs in older patients (>50 y). Patients younger than 30 years are rarely reported.[2, 5]

Patient education

Patients should be taught proper bladder and bowel care. Education regarding the identification of early symptoms and signs of disease recurrence also is required. Educate the patient’s family and/or caregiver about proper skin care and nutrition and about patient transfer requirements. (See Presentation.)

Foix-Alajouanine syndrome is a subacute disorder that gradually evolves over 1-5 years.[2] Affected patients initially are spastic but eventually develop flaccid paralysis of the limbs and may become wheelchair bound. Death can occur with terminal sepsis or other sequelae.

The prognosis is poor if treatment is not administered before neurologic deterioration occurs. Successful embolization and/or surgical interruption of the draining veins can halt the progression of symptoms and provide clinical improvement in many patients. Operations, if successful, are permanent modalities of treatment. After embolization, recanalization may occur, but this is rarely seen if the draining vein is filled with glue.[5]

Patients present with increasing unilateral and/or bilateral weakness, dysesthesias, and numbness or tingling in the lower extremities, which may be symmetrical or asymmetrical.[6] Early problems with bowel, bladder, and sexual function are common.[7]

After brief exertion, symptoms begin as a heavy feeling in the legs that generally improves with rest. The symptoms gradually worsen over months, and the patient may have difficulty standing for long periods. Frequent falls can be a problem. Urinary and fecal incontinence eventually occur.

Complaints of nonradiating lower back pain in the lumbosacral or coccygeal regions are common. This may initially be interpreted as sciatica. Weakness or numbness eventually can progress to the upper extremities.

In most patients, Foix-Alajouanine syndrome follows a protracted course over a few years before a diagnosis is made.[5] In a minority of patients, however, an acute onset of symptoms is reported.

A physical examination can reveal the following:

• Neurologic examination - Reveals an alert patient with normal mentation

• Mental status, speech, language, and cranial nerve function - Generally are normal

• Unsteadiness of gait - Common; may be halting in nature but on a narrow base

• Spastic or flaccid paraparesis and a sensory level below the lesion

• Deep tendon reflexes - May be normal or increased

• Bilateral Babinski signs - May be present, as may clonus; upper motor neuron and lower motor neuron signs may be seen simultaneously[5]

• Vibration and joint position senses - Usually are preserved

• Rectal sphincter tone - Frequently is diminished

Patients may suffer recrudescence of symptoms, lack of improvement, or rapid neurologic deterioration (eg, flaccid, areflexic paraplegia with complete loss of sensation below the lesion).

Angiographic examination contains an element of risk, especially in older patients; it may compromise local circulation, which can aggravate neurologic deficits. With regard to surgery, a fatal postoperative outcome is not uncommon.

Catheter spinal angiography remains the criterion standard for the diagnosis of Foix-Alajouanine syndrome and spinal dural arteriovenous (AV) fistulas. It may demonstrate specific arterial feeders and draining dorsal veins.

With regard to lab studies, obtain serum vitamin B-12 levels to exclude subacute, combined degeneration caused by vitamin B-12 deficiency. Vitamin B-12 levels should be normal in Foix-Alajouanine syndrome.

Consider testing for infections caused by human immunodeficiency virus (HIV), human T-cell leukemia virus type 1 (HTLV1), Lyme disease, and syphilis, as all can produce myelopathies.

Neurophysiologic studies such as somatosensory evoked potentials may be useful in evaluating Foix-Alajouanine syndrome. They may reveal a conduction block in the large fiber sensory system rostral to the lesion either at or below the sensory level.

Electromyography and nerve conduction studies can exclude a peripheral nerve lesion or motor neuron disease. Thus, they also can assist in the localization of the lesion to the spinal cord.

CT scanning and MRI

Computed tomography (CT) scanning and magnetic resonance imaging (MRI) studies may be normal during the early stages of Foix-Alajouanine syndrome.

With disease progression, T1-weighted MRI scans reveal swelling of the cord and decreased signal intensity peripherally within the affected spinal cord segments. On T2-weighted images, the spinal cord lesions are hyperintense in central locations.

Contrast administration often produces serpentine areas of enhancement and reveals the presence of enlarged, tortuous vessels in the subarachnoid space with associated "flow void" phenomena.

Most spinal dural AV fistulas occur in the thoracolumbar spinal cord; less than 6% are cervical or sacral in location.[7]

Angiography

Initially, MR angiograms can more correctly predict the site and extent of the fistula prior to the use of the more invasive technique of catheter angiography. MR angiograms generally demonstrate flow in serpentine perimedullary vessels.

As previously stated, catheter spinal angiography remains the criterion standard for the diagnosis of Foix-Alajouanine syndrome and spinal dural AV fistulas. It may demonstrate specific arterial feeders and draining dorsal veins.

Myelography

Myelographic studies are not required but may nonetheless be useful in Foix-Alajouanine syndrome. Irregular filling defects frequently are observed with myelography. Conventional CT myelography also may be useful.

Histologic findings include redundancy of veins within the cord and subarachnoid space. The dilated vessels have enormously thickened, hyalinized walls composed of abundant collagen and smooth muscle cells. Vascular thrombosis may be present. The gliotic spinal cord parenchyma beneath the dilated veins may show coagulative necrosis with exudation, fibrosis of the nerve roots, and ascending degeneration of the dorsal columns.

Proliferation of intramedullary blood vessels frequently is observed and may be accompanied by fibrinoid degeneration of the vessel walls. Hemosiderin deposition may be present, is predominantly perivascular, and is indicative of previous bleeding. (See the images below.)[4]

Photomicrograph of the cervical spinal cord region showing a thickened subarachnoid vein with a thrombotic occlusion (hematoxylin and eosin stain).

Photograph of the cervical spinal cord illustrating dilated, abundant subarachnoid veins (hematoxylin and eosin stain).

Photomicrograph of the cervical spinal cord region demonstrating several dilated, hyalinized intraparenchymal vessels (hematoxylin and eosin stain).

Photomicrograph of the cervical spinal cord depicting ischemic necrosis of the parenchyma (hematoxylin and eosin stain).

The choice of treatment for Foix-Alajouanine syndrome is either endovascular embolization or surgical ligation of the fistula;[5]  in some cases, both modalities are used.[7]

Successful embolization of the vascular malformation can halt progression of the disease and may result in clinical improvement. Vascular embolization procedures are required in patients in whom surgery is contraindicated.

Many authors consider direct surgical obliteration of spinal dural arteriovenous (AV) fistulas to be the criterion standard of management, since the surgery reportedly provides better disability scores and lower recurrence rates than do embolization procedures.[7, 8] Moreover, surgical management is required if lesions are not amenable to endovascular treatment or if such therapy has failed.[7]

Consultations

An interventional neuroradiologist with expertise in vascular embolization may be able to offer initial, noninvasive therapy.

Neurosurgical consultation is recommended unless the medical condition of the patient precludes the possibility of surgical intervention.

Inpatient care

Perform a daily postoperative neurologic examination to document improvement or deterioration. Address proper bladder and bowel care.

Outpatient care

Further outpatient care in a rehabilitation center may be required. Proper bladder care may be needed, and an indwelling catheter may be required for several months.

Perform follow-up angiographic studies if symptoms recur. Angiography at 2- to 3-month intervals is recommended for patients who have not made a full recovery.

Activity restrictions depend entirely on the patient's neurologic condition.

Endovascular embolization is the least invasive means of therapy and should be attempted if an experienced interventional radiologist is available. The success of endovascular treatment is believed to be highly dependent on complete occlusion of the proximal radiculomedullary draining vein and on the site of the fistula itself.[7]

Embolization with a liquid polymer, such as isobutyl 2-cyanoacrylate (IBCA) or n -butyl 2-cyanoacrylate (NBCA), is considered preferential to embolization with particles, such as those made from polyvinyl alcohol (PVA), because particle use is associated with a higher recurrence rate.[5] Occlusion performed with liquid polymers is successful in 70-90% of cases.[5, 7]

If arterial feeders of fistulas are discovered by imaging studies to involve tributaries of the anterior spinal artery, embolization is not possible due to the risk of spinal cord ischemia and/or infarction.[5]

A novel embolization technique utilizing two microcatheters to selectively place the embolic agent has been developed and tested on a limited number of patients in South Korea.[9] This procedure may have a lower recanalization rate than conventional methods, though does not appear to be widely available at this time for treatment of arteriovenous fistulas.

Surgical intervention consists of an intradural interruption of the vein draining the fistula. This procedure reduces venous flow (thus diminishing congestion and venous hypertension) and prevents subsequent edema. These measures improve cord perfusion.

A meta-analysis of patients who underwent spinal dural AV fistula operations showed that almost 98% of the surgical procedures were technically successful.[5] The use of intraoperative micro-Doppler evaluation was helpful in one study in increasing the safety of the surgical procedure and in minimizing surgical exposure.[10]

Complications in the form of rapid loss of neurologic function after surgery (weakness or loss of bowel and bladder control) have been observed. These complications are attributed to lack of preoperative identification of the disease process and incorrect recognition of the site of the lesion.

Perform surgical treatment as soon as possible, since the longer the duration of venous hypertension, the greater the magnitude of irreversible neurologic impairment. Prognosis for total recovery is poor if treatment is not rendered early, before neurologic deterioration occurs.

With few exceptions, pharmacologic intervention is used only for symptomatic treatment of Foix-Alajouanine syndrome. Agents used in this therapy include the following:

• Corticosteroids - Dexamethasone

• Anticoagulants - Heparin

• Antibiotics - Including amoxicillin and trimethoprim-sulfamethoxazole (TMP-SMZ); for bowel and bladder infections and terminal sepsis

Class Summary

Anti-inflammatory medications may improve neurologic disability during acute symptoms.

Dexamethasone (Baycadron)

Dexamethasone is a synthetic adrenocortical steroid. During the acute phase of Foix-Alajouanine syndrome, intravenous (IV) dexamethasone may improve neurologic disability.

Class Summary

If angiographic evidence of thrombosis exists, anticoagulation with heparin may be indicated.

Heparin

Heparin inhibits reactions that lead to blood clotting and the formation of fibrin clots (in vitro and in vivo). The drug is administered intravenously; oral administration is not effective. Adjust the dosage according to the patient's coagulation test results. The dosage is considered adequate when the activated partial thromboplastin time (aPTT) is 1.5-2 times normal. Continue heparin administration for at least 48 hours after the therapeutic value of aPTT has been reached.

Class Summary

Institute proper antibiotic therapy as indicated for bladder or bowel infections and for terminal sepsis, which frequently has a pulmonary etiology.

Amoxicillin (Moxatag)

Amoxicillin is an analogue of ampicillin with broad-spectrum bactericidal activity against many gram-positive and gram-negative organisms.

Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS, Septra DS)

TMP-SMZ is a synthetic, broad-spectrum antibacterial combination that inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid, resulting in the inhibition of bacterial growth.