Neuro-behcet disease

Behçet’s disease is recognized as a disease that cause inflammatory perivasculitis, inflammation of the tissue around a blood or lymph vessel, in practically any tissue in the body. Usually, prevalent symptoms include canker sores or ulcers in the mouth and on the genitals, and inflammation in parts of the eye.^[1] In addition, patients experience severe headache and papulopustular skin lesions as well. The disease was first described in 1937 by a Turkish dermatologist, Dr. Hulusi Behçet. Behcet's disease is most prevalent in the Middle East and the Far East regions; however, it is rare in America regions.^[2]

The Behcet disease with neurological involvement, Neuro-Behçet's disease (NBD), involves Central nervous system damage in 5–50% of cases.^[3] The high variation in the range is due to study design, definition of neurological involvement, ethnic or geographic variation, availability of neurological expertise and investigations, and treatment protocols.

Causes

Because the cause of the Behcet's disease is unknown, the cause responsible for Neuro-behcet's disease is unknown as well. Inflammation starts mainly due to immune system failure. However, no one knows what factor trigger the initiation of auto-immune disease like inflammation. Because the cause is unknown, it is impossible to eliminate or prevent the source that causes the disease. Therefore, treatments are focused on how to suppress the symptoms that hinders daily life activities.^[4]

Epidemiology

In one study of 387 Behcet's disease (BD) patients that has been done for 20 years, 13 % of men with BD developed to NBD and 5.6 % of women developed to NBD. Combining all statistical reports, approximately 9.4 % (43 of 459) BD patients advanced to NBD. In addition, men were 2.8 times more likely to experience NBD than women. This fact indicates possible gender-based pathology.^[5][6][7] In speaking about age of NBD patients, the general range was between 20 to 40. NBD patients with age less than 10 or more than 50 were very uncommon.

Types of Neuro-Behcet's disease

There are two types of Neuro-Behcet'ss disease: Parencymal and Non-Parenchymal. The two types of Neuro-Behcet's disease rarely occur in the same person. It is suggested that the pathogenesis of the two types are probably different.[3] Statistics indicate that approximately 75 % (772 of 1031) BD patients advanced to parenchymal NBD while 17.7 % (183 of 1031) of BD patients advanced to non-parenchymal NBD. The remaining 7.3 % were not able to be categorized.

Parenchymal

If one experiences parenchymal Neuro-Behcet's disease, meningoencephalitis, inflammation of brain, primarily occurs. The target areas of parenchymal NBD include brainstem, spinal cord, and cerebral regions. Sometimes it is hard to determine the affected area because symptoms are asymptomatic.^[8]

Non-parenchymal

In non-parenchymal NBD, vascular complications such as cerebral venous thrombosis primarily occurs. Other distinct characteristics include Intracranial aneurysm and extracranial aneurysm. In most cases, veins are much more likely to be affected than arteries. Venous sinus thrombosis is the most frequent vascular manifestation in NBD followed by cortical cerebral veins thrombosis. On the other hand, thrombosis and aneurysms of the large cerebral arteries are rarely reported.^[9]

Others

Peripheral nervous system involvement is rarely reported (~0.8%). In this case, Guillain-Barré syndrome, sensorimotor neuropathy, mononeuritis multiplex, autonomic neuropathy, and subclinical nerve-conduction abnormalities are observed.

Some of the syndromes are not common but recognized for the relation to NBD such as acute meningeal syndrome, tumour-like neuro-Behçet’s disease, psychiatric symptoms and optic neuropathy

Clinical characteristics

The initial signs and symptoms of NBD are usually very general. This makes NBD hard to diagnose until the patients experience a severe neurological damage. In addition, the combination of symptoms varies among patients.

Parenchymal Neuro-behcet's disease

The main symptoms is meningoencephalitis which happens in ~75 % of NBD patients. Other general symptoms of Behcet's disease are also present among parenchymal NBD patients such as fever, headache, genital ulcers, genital scars, and skin lesions. When brainstem is affected, ophthalmoparesis, cranial neuropathy, and cerebellar or pyramidal dysfunction may be observed. When cerebral hemispheric involvement happens, encephalopathy, hemiparesis, hemisensory loss, seizures, and dysphasia, and mental changes include cognitive dysfunction and psychosis may be observed. As for the spinal cord involvement, pyramidal signs in the limbs, sensory level dysfunction, and, commonly, sphincter dysfunction may be observed.

Some of the symptoms are less common such as stroke (1.5 %), epilepsy (2.2-5 %), brain tumor, movement disorder, acute meningeal syndrome, and optic neuropathy.

Non-parenchymal Neuro-behcet's disease

Because Non-parenchymal NBD targets vascular structures, the symptoms arise in the same area. The main clinical characteristic is the Cerebral venous thrombosis (CVT). If one experiences CVT, a clot in one of the blood vessels in the brain blocks the blood flow and may result in stroke. This happens in the dural venous sinuses. Stroke-like symptoms such as confusion, weakness, and dizziness may be monitored. Headache tends to worsen over the period of several days.

Some of the less common symptoms include intracranial hypertension and intracranial aneurysms.

Diagnosis

Although there is a diagnostic criterion for Behcet's disease, one for Neuro-behcet's disease does not exist. Three diagnostic tools are mainly used

Blood test

60-70 % of Japanese and Turkish patients were tested to possess HLA-B51, HLA-B serotype. These patients showed 6 times risk of getting BD. However, the same criteria is not ideal to be applied for Europeans because only 10-20 % of European patients showed to possess HLA-B51.

Cerebrospinal fluid level

Cerebrospinal fluid is a clear bodily fluid that occupies the subarachnoid space and the ventricular system around and inside the brain. It is revealed that 70-80 % of Parenchymal NBD patients show altered CSF constituents. The observed different is 1) Elevated CSF protein concentration (1 g/dL), 2) Absence of oligoclonal band, and 3) elevated CSF cell count (0–400×10⁶ cells/L) in the body.

Magnetic resonance imaging test

MRI is the most sensitive imaging technique that can be used for diagnosing NBD. As for the parenchymal NBD, medical doctors mainly monitor the upper brainstem lesion. In fact, it is possible that lesions extends to thalamus and basal ganglia. Another advantage of using MRI is the ability to perform Diffusion-weighted imaging, or [diffusion MRI]. This technique is the most sensitive tool to image an acute infarct. In the case of NBD, Diffusion MRI can determine whether the lesion were due to cerebral infarction. In other words, it can distinguish NBD from non-NBD neural disease. When only spinal cord is affected by NBD, brain looks perfectly normal when scanned by MRI. Therefore, it is necessary to scan the spinal cord as well when diagnosing possible NBD involvement.^[10] As for the non-parenchymal NBD, venous sinus thrombosis can be detected.

Others

"...Despite its rarity, the patient’s ethnic background and the typical radiographic findings should prompt the clinicians to include NBD in the differential diagnosis of optic neuritis and demyelinating disease in the young..."[5]. This quote indicates that even common symptoms such as headache should be recognized as the sign for possible NBD considering the patient's ethnic background.

Treatment

No definite standards of NBD treatment have been set. Therefore, it is completely up to medical doctors on how to treat NBD. However, there is a consensus among medical doctors that in cases of inflammatory parenchymal disease, "corticosteroids should be given as infusions of intravenous methylprednisolone followed by a slowly tapering course of oral steroids." It is suggested that therapy should be continued for a perioud of time even when the symptoms get suppressed because early relapse may occur. Sometimes, the medical doctors may suggest different steroid depends on the nature of the disease, severity, and the response to steroids. According to several studies, parenchymal NBD patients successfully suppress the symptoms with the prescribed steroids. As for non-parenchymal patients, there is no general consensus on how to treat the disease. The reason is that the mechanisms of cerebral venous thrombosis in BD are still poorly understood. Some doctors use anti-coagulants to prevent a clot. On the other hand, some doctors only give steroids and immunosuppressants alone. .^[11][12]

Conclusion

Because Behcet's disease is observed on limited regions, people's attention towards Behcet's disease is low. In addition, it is hard to conduct a clinical experiment in places such U.S because there is so limited number of patients. As a result, there is limited number of research going on in the world to find out how to ultimately cure the disease. Because the cause of the disease is currently unknown, it is practically impossible for medical doctors and scientists to come up with a treatment.

References

1. ^ Serdaroflu P, Yazici H, Ozdemir C, Yurdakul S, Bahar S, Aktin E (1989) Neurologic involvement in Behçet’s syndrome. A prospective study. Arch Neurol 46(3):265–269
2. ^ Yazici H, Fresko I, Yurdakul S. (2007) Behçet’s syndrome: disease manifestations, management, and advances in treatment. Nat Clin Pract Rheumatol (3): 148–55.
3. ^ Farah S, Al-Shubaili A, Montaser A. (1998) Behçet’s syndrome: a report of 41 patients with emphasis on neurological manifestations. J Neurol Neurosurg Psychiatry (64): 382–84.
4. ^ Akman-Demir G, Serdaroglu P, Tasçi B, and the Neuro-Behçet Study Group (1999) Clinical patterns of neurological involvement in Behçet’s disease: evaluation of 200 patients. Brain 122:2171–2182.
5. ^ Barros R, Santos E, Moreira B, et al. Clinical characterization and pattern of neurological involvement of Behçet’s disease in fi fteen Portuguese patients. Clin Exp Rheumatol 2007; 24
6. ^ Ashjazadeh N, Borhani Haghighi A, Samangooie S, Moosavi H. Neuro-Behçet’s disease: a masquerader of multiple sclerosis. A prospective study of neurologic manifestations of Behçet’s disease in 96 Iranian patients. Exp Mol Pathol 2003; 74: 17–22.
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8. ^ Kidd D, Steuer A, Denman AM, Rudge P. Neurological complications of Behçet’s syndrome. Brain 1999; 122: 2183–94.
9. ^ Tunc R, Saip S, Siva A, Yazici H. Cerebral venous thrombosis is associated with major vessel disease in Behçet’s syndrome. Ann Rheum Dis 2004; 63: 1693–94.
10. ^ Turker H, Terzi M, Bayrak O, Cengiz N, Onar M, Us O. Visual evoked potentials in diff erential diagnosis of multiple sclerosis and neurobehçet’s disease. Tohoku J Exp Med 2008; 216: 109–16.
11. ^ Akman-Demir G, Serdaroglu P, Tasçi B. Clinical patterns of neurological involvement in Behçet’s disease: evaluation of 200 patients. The Neuro-Behçet Study Group. Brain 1999; 122: 2171–82.
12. ^ Al-Fahad S, Al-Araji A. Neuro-Behçet’s disease in Iraq: a study of 40 patients. J Neurol Sci 1999; 170: 105–11.