eMedicine Specialties > Neurology > Neuro-vascular Diseases

Foix-Alajouanine Syndrome

Cheryl Ann Palmer, MD, Professor, Departments of Pathology and Neurology, University of Alabama at Birmingham School of Medicine; Consulting Staff, Departments of Pathology and Neurology, University of Alabama at Birmingham Hospital; Consulting Staff, Departments of Pathology and Neurology, Veteran Affairs Medical Center; Consulting Staff, Department of Pathology, Children's Hospital of Alabama

Updated: Dec 10, 2008

Introduction

Background

Foix and Alajouanine first described Foix-Alajouanine syndrome in 2 young men (aged 31 and 37 y) in 1926.¹ The patients presented with subacute myelopathy, and autopsy revealed spinal cord necrosis and abnormally dilated and tortuous vessels situated primarily on the spinal cord surface. The underlying pathology was believed to be a dural arteriovenous (AV) fistula. Krause first attempted surgical treatment in 1911² , performing a laminectomy to expose the abnormal segments of the spinal cord.

Historically eponymic, the syndrome now has many other names in the literature — angiodysgenetic necrotizing myelopathy, subacute necrotizing myelopathy, and venous congestive myelopathy.³

Pathophysiology

Foix-Alajouanine syndrome is an arteriovenous 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 to white matter) structures are more severely involved. Masses of enlarged, tortuous, and 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.

The enlarged, abnormal veins are associated with dural arteriovenous (AV) shunt or fistulas, usually intradurally but rarely extradurally. These AV shunts are associated with reflux of arterial blood into the venous drainage of the cord. This results in increased venous pressure in the affected regions of the spinal cord, often leading to ischemic injury.⁴

Frequency

United States

Foix-Alajouanine syndrome is a rare entity. No specific statistics are available, but the condition is likely underdiagnosed.

International

Foix-Alajouanine syndrome also is rare internationally.

Mortality/Morbidity

• Foix-Alajouanine syndrome is a subacute disorder that gradually evolves over 1-5 years.⁴
• 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.

Race

No racial predilection has been observed.

Sex

Male-to-female ratio is nearly 5:1.⁵

Age

Foix-Alajouanine usually occurs in older patients (>50 y).⁴ Patients younger than 30 years are rarely reported.

Clinical

History

• Patients present with increasing unilateral and/or bilateral weakness, dysesthesias, and numbness or tingling in the lower extremities, which may be symmetric or asymmetric.
• Early problems with bowel, bladder, and sexual function are common.
• Symptoms begin after brief exertion as a heavy feeling in the legs that generally improves with rest.
• 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 appear.
• Complaints of nonradiating lower back pain in the lumbosacral or coccygeal regions are common. This may be initially interpreted as sciatica.
• Weakness or numbness eventually can progress to the upper extremities.
• An acute onset of symptoms is reported in a minority of patients; a protracted course over a few years is more common in most patients before a diagnosis is made.⁵

Physical

• Neurologic examination reveals an alert patient with normal mentation.
• Normal mental status, speech, and language and cranial nerve function are generally present.
• Unsteadiness of gait, which also may be halting in nature but on a narrow base, is common.
• Spastic or flaccid paraparesis and a sensory level below the lesion can be observed.
• 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.

Causes

• The etiology of this syndrome is not well understood.
  • Most patients have an arteriovenous (AV) fistula in the lower thoracic dura.
  • One 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.³
  • 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 arteriovenous malformations, which are assumed to be congenital abnormalities, although the specificity for the spinal cord is not easily explained.

Differential Diagnoses

Other Problems to Be Considered

Lumbosacral disk syndromes
Cervical disk syndromes
Lumbosacral spondylosis
Primary or metastatic neoplastic disease
Spinal arachnoiditis
Spinal artery thrombosis
Spinal injury
Hereditary spastic paraplegias

Workup

Laboratory Studies

• Obtain serum vitamin B-12 levels to exclude subacute combined degeneration caused by vitamin B-12 deficiency. B-12 levels should be normal in Foix-Alajouanine syndrome.
• Consider testing for infections caused by human T-cell leukemia virus type 1 (HTLV1) or human immunodeficiency virus (HIV), as both can produce myelopathy.

Imaging Studies

• CT or MRI studies
  • CT or MRI studies may be normal during the early stages of Foix-Alajouanine syndrome.
  • With disease progression, T1-weighted MRI images 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.
• Myelographic studies are not required but may be useful.
  • Irregular filling defects frequently are observed with myelography.
  • Conventional CT myelography also may be useful.
• MR angiograms initially more correctly predict the site and extent of the fistula prior to the more invasive catheter angiography. They generally show flow in serpentine perimedullary vessels.
• Catheter spinal angiography remains the criterion standard for the diagnosis of Foix-Alajouanine syndrome. It may demonstrate specific arterial feeders and draining dorsal veins.

Other Tests

• Neurophysiologic studies such as somatosensory evoked potentials may be useful in evaluating this condition. 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.

Histologic Findings

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 (see Media files 2-4). Hemosiderin deposition may be present, predominantly perivascular, and is indicative of previous bleeding.³

Treatment

Medical Care

• The choice of treatment is between endovascular embolization and surgical ligation of the fistula.⁵
• Endovascular embolization is the least invasive means of therapy and should be attempted if an experienced interventional radiologist is available.
• Successful embolization of the vascular malformation with various agents can be performed. This can halt progression of the disease and may result in clinical improvement. Vascular embolization procedures are required in patients for whom surgery is contraindicated.
• Embolization with liquid polymers is advocated over particles because the use of particles leads to a higher recurrence rate.⁵ Occlusion done with liquid polymers is successful in 44-100% of cases.⁵
• 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

Surgical Care

• 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 with spinal dural AV fistula operations showed that almost 98% of the surgical procedures were technically successful.⁵
• 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.

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.

Diet

No specific dietary restrictions are necessary.

Activity

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

Medication

With few exceptions, pharmacologic intervention only is used for symptomatic treatment.

Corticosteroids

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

Dexamethasone (Decadron, Dexasone)

Synthetic adrenocortical steroid; during acute phase of Foix-Alajouanine syndrome, IV dexamethasone may improve neurologic disability.

Dosing

Adult

Initially administer 0.5-10 mg IV/IM, followed by 4 mg IV/IM q6h until symptoms are controlled; taper gradually thereafter

Pediatric

Not established

Interactions

Phenytoin, phenobarbital, and rifampin may enhance metabolic clearance, resulting in decreased blood levels; when administered concomitantly with a potassium-depleting diuretic, observe patients closely for hypokalemia

Contraindications

Documented hypersensitivity, systemic fungal infections

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Enhanced effects in patients with hypothyroidism or cirrhosis; use aspirin cautiously with corticosteroids in hypoprothrombinemia

Anticoagulants

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

Heparin

Inhibits reactions that lead to clotting of blood and formation of fibrin clots, both in vitro and in vivo; administer IV, as not effective by oral administration; adjust dosage according to patient's coagulation test results; dosage is considered adequate when the aPTT is 1.5-2 times normal; continue for at least 48 h after therapeutic value of aPTT has been reached.

Dosing

Adult

Administer loading dose of 5000 U IV followed by 1000-2000 U/h IV

Pediatric

Not established

Interactions

Caution with drugs that interfere with platelet aggregation reactions (eg, aspirin, phenylbutazone, ibuprofen, indomethacin) as they may induce bleeding

Contraindications

Documented hypersensitivity; active bleeding states; severe thrombocytopenia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

A higher incidence of bleeding has been reported in women >60 y; increased resistance frequently encountered in fever, thrombosis, and infections with increased tendency for thrombosis

Antibiotics

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

Amoxicillin (Amoxil, Polymox, Trimox)

Analog of ampicillin with broad-spectrum bactericidal activity against many gram-positive and gram-negative organisms.

Dosing

Adult

250 mg PO tid for 10-14 d

Pediatric

Not established

Interactions

Can reduce efficacy of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Periodically assess renal, hepatic, and hematopoietic function; keep in mind the possibility of superinfection with mycotic or bacterial pathogens; adjust dose in patients with renal impairment

Trimethoprim and sulfamethoxazole (Bactrim)

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.

Dosing

Adult

2 tabs (400 mg sulfamethoxazole and 80 mg trimethoprim) PO q12h for 10-14 d

Pediatric

Not established

Interactions

May prolong PT in patients receiving warfarin (anticoagulant); increased incidence of thrombocytopenia with purpura reported in older patients receiving thiazide diuretics; increased serum levels of both dapsone and TMP may occur when both medications are administered concomitantly; phenytoin's hepatic clearance may be decreased and the half-life prolonged; sulfonamides can displace MTX from plasma protein-binding sites, thus increasing free MTX concentrations; may potentiate MTX effects in bone marrow depression; hypoglycemic response of sulfonylureas may be increased with concurrent administration of both medications; may decrease renal clearance of zidovudine, increasing zidovudine levels

Contraindications

Documented hypersensitivity; documented megaloblastic anemia from folate deficiency; avoid use in pregnant mothers at term and in nursing mothers

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Discontinue at the first appearance of skin rash or sign of adverse reaction; obtain CBCs frequently; if significant reduction in the count of any formed blood element is noted, discontinue therapy; goiter production, diuresis, and hypoglycemia can occur; high IV doses or prolonged infusions may cause bone marrow depression manifested as thrombocytopenia, leukopenia, or megaloblastic anemia; caution in patients with possible folate deficiency (eg, chronic alcoholics, older patients, patients with malabsorption syndrome, those receiving anticonvulsant therapy); hemolysis may occur in G-6-PD deficient individuals; if signs of bone marrow depression occur, give leucovorin prn to restore normal hematopoiesis (oral leucovorin, 5-15 mg/d is recommended)
Because of their unique immune dysfunction, patients with AIDS may not tolerate or respond to TMP-SMZ; caution in patients diagnosed with renal or hepatic impairment; administer adequate fluid to prevent crystalluria and stone formation; perform urinalyses and renal function tests during therapy

Follow-up

Further Inpatient Care

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

Further 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.

Complications

• Recrudescence of symptoms, lack of improvement, or rapid neurologic deterioration (eg, flaccid, areflexic paraplegia with complete loss of sensation below the lesion) may occur.
• A postoperative fatal outcome is not uncommon.
• Angiographic examination contains an element of risk, especially in older patients. It may compromise local circulation, which may aggravate neurologic deficits.

Prognosis

• 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.
• Symptoms that generally respond well to treatment are gait difficulties and muscle strength. Micturition, pain, and muscle spasms are symptoms that often do not respond as well.⁵
• Operations, if successful, are permanent modes of treatment. After embolization, recanalization may occur, but this is rarely seen if the draining vein is filled with glue.⁵

Patient Education

• Teach patients proper bladder and bowel care.
• Education to identify early symptoms and signs of disease recurrence also is required.
• Educate family and/or caregiver about proper care of skin, nutrition, and patient transfer requirements.

Miscellaneous

Medicolegal Pitfalls

• In the early stages of the Foix-Alajouanine syndrome, symptomatology may mimic a polyradiculopathy or anterior horn cell disorder. By the time involvement of upper motor neurons or sacral segments makes the diagnosis of Foix-Alajouanine inescapable, patients may suffer from considerable neurologic deficits.⁵
• Not infrequently, patients are unsuccessfully operated for a lumbar disc prolapse.⁵
• Patient presentation, and most especially, imaging findings, can lead to the incorrect diagnosis of spinal cord tumor.

Multimedia

Media file 1: Gross photograph of the dorsal surface of the spinal cord showing dilated and tortuous vessels

Media file 2: Photomicrograph of the cervical spinal cord region showing a thickened subarachnoid vein with a thrombotic occlusion (hematoxylin and eosin stain)

Media file 3: Photograph of the cervical spinal cord illustrating dilated, abundant subarachnoid veins (hematoxylin and eosin stain).

Media file 4: Photomicrograph of the cervical spinal cord region demonstrating several dilated, hyalinized intraparenchymal vessels (hematoxylin and eosin stain).

Media file 5: Photomicrograph of the cervical spinal cord depicting ischemic necrosis of the parencnyma (hematoxylin and eosin stain).

References

1. Foix CH, Alajouanine T. La myelite necrotique subaigue. Rev Neurol. 1926;46:1-42.

2. Krause F. Chirurgie des Gehirns und Ruckenmarks nach eigenen Erfarungen. Berlin: Urban & Schwarzenberg; 1911.

3. Rodriguez FJ, Crum BA, Krauss WE, Scheithauer BW, Giannini C. Venous congestive myelopathy: a mimic of neoplasia. Mod Pathol. May 2005;18(5):710-8. [Medline].

4. Mishra R, Kaw R. Foix-Alajouanine syndrome: an uncommon cause of myelopathy from an anatomic variant circulation. South Med J. May 2005;98(5):567-9. [Medline].

5. Jellema K, Tijssen CC, van Gijn J. Spinal dural arteriovenous fistulas: a congestive myelopathy that initially mimics a peripheral nerve disorder. Brain. Dec 2006;129:3150-64. [Medline].

6. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 12-1992. A 64-year-old woman with the abrupt onset of paraparesis after 10 months of increasing episodic leg weakness. N Engl J Med. Mar 19 1992;326(12):816-24. [Medline].

7. Criscuolo GR, Oldfield EH, Doppman JL. Reversible acute and subacute myelopathy in patients with dural arteriovenous fistulas. Foix-Alajouanine syndrome reconsidered. J Neurosurg. Mar 1989;70(3):354-9. [Medline].

8. Graham DI, Lantos PL, eds. Foix-Alajouanine syndrome. In: Greenfield's Neuropathology. 6^th ed. York, NY: Oxford Univ Press; 1997:1101-1104.

9. Kneisley LW, Dominguez MR, Bignami A, Rossier AB. Paraplegia following surgery in Foix and Alajouanine syndrome. (Arteriovenous malformation of the spinal cord). Paraplegia. Feb 1980;18(1):33-41. [Medline].

10. Koeppen AH, Barron KD, Cox JF. Foix-Alajouanine syndrome. Acta Neuropathol (Berl). 1974;29(3):187-97. [Medline].

11. Minami S, Sagoh T, Nishimura K, et al. Spinal arteriovenous malformation: MR imaging. Radiology. Oct 1988;169(1):109-15. [Medline].

12. Schmidbauer M, Lassmann J, Pilz P, et al. Subacute diencephalic angioencephalopathy: an entity similar to angiodysgenetic necrotizing encephalopathy and Foix-Alajouanine disease. J Neurol. Aug 1992;239(7):379-81. [Medline].

13. Welsh CT, Palmer CA, Townsend JJ. Radiologic pathologic correlation of spinal dural arteriovenous fistula (Foix-Alajouanine syndrome). Int J Neurorad. 1998;4 (1):51-55.

14. Wrobel CJ, Oldfield EH, Di Chiro G, et al. Myelopathy due to intracranial dural arteriovenous fistulas draining intrathecally into spinal medullary veins. Report of three cases. J Neurosurg. Dec 1988;69(6):934-9. [Medline].

15. Zweifler RM. Management of acute stroke. South Med J. Apr 2003;96(4):380-5. [Medline].

Keywords

angiodysgenetic necrotizing myelopathy, spinal dural arteriovenous fistula, subacute necrotizing myelopathy, venous congestive myelopathy, spinal cord necrosis, dural arteriovenous fistula, AV malformation of the spinal cord, spinal cord malformation, laminectomy

Contributor Information and Disclosures

Author

Cheryl Ann Palmer, MD, Professor, Departments of Pathology and Neurology, University of Alabama at Birmingham School of Medicine; Consulting Staff, Departments of Pathology and Neurology, University of Alabama at Birmingham Hospital; Consulting Staff, Departments of Pathology and Neurology, Veteran Affairs Medical Center; Consulting Staff, Department of Pathology, Children's Hospital of Alabama
Cheryl Ann Palmer, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuropathologists, Medical Association of the State of Alabama, Society for Neuro-Oncology, and Southern Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Richard M Zweifler, MD, Chief of Neurology, Sentara Healthcare, Norfolk, VA
Richard M Zweifler, MD is a member of the following medical societies: American Academy of Neurology, American Heart Association, American Medical Association, American Stroke Association, Royal Society of Medicine, and Stroke Council of the American Heart Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Howard S Kirshner, MD, Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine; Director, Vanderbilt Stroke Center; Program Director, Stroke Service, Vanderbilt Stallworth Rehabilitation Hospital; Consulting Staff, Department of Neurology, Nashville Veterans Affairs Medical Center
Howard S Kirshner, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Heart Association, American Medical Association, American Neurological Association, American Society of Neurorehabilitation, National Stroke Association, Phi Beta Kappa, and Tennessee Medical Association
Disclosure: Boehringer Ingelheim Honoraria Speaking and teaching; BMS/Sanofi Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; Novartis Consulting fee Review panel membership

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Helmi L Lutsep, MD, Professor, Department of Neurology, Oregon Health and Science University; Associate Director, Oregon Stroke Center
Helmi L Lutsep, MD is a member of the following medical societies: American Academy of Neurology and American Stroke Association
Disclosure: Co-Axia Consulting fee Review panel membership; Talecris Consulting fee Review panel membership; AGA Medical Consulting fee Review panel membership; Boehringer Ingelheim Honoraria Speaking and teaching; Boston Scientific Honoraria Speaking and teaching; Concentric Medical None Review panel membership; Northstar Neuroscience  Review panel membership; ev3 Consulting fee Review panel membership

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Abhik Ray-Chaudhury, MD to the development and writing of this article.

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