Neuro-Behcet’s Disease - Symptoms, Diagnosis, and Treatment

Introduction:

Behcet's disease (BD) is an autoimmune vasculitis disorder that affects various systems in the body, involving small, medium, and large blood vessels. Its exact cause is not well understood. The common clinical manifestations include recurrent aphthous ulcers (small, painful sores found inside the mouth) genital ulcers, skin lesions(damaged areas on the skin's surface), and bilateral uveitis (inflammation occurring in both eyes simultaneously). Neurological symptoms are less frequent, occurring in fewer than 10 percent of cases, and usually appear about five to six years after the initial non-neurological symptoms. This presentation is referred to as Neuro-Behcet's disease (NBD) and is associated with a more challenging prognosis for BD.

What Is Neuro-Behcet's Disease?

Neuro-Behcet's disease (NBD) is when someone with Behcet's disease (BD) experiences neurological symptoms or signs. These symptoms can include issues with the brainstem, multiple sclerosis-like presentations, movement problems, inflammation of the brain and its membranes (meningoencephalitis syndrome), spinal cord issues, cerebral venous sinus thrombosis (CVST), and increased pressure inside the head (intracranial hypertension). NBD can be divided into two types: parenchymal, which is more common and affects the brain stem, hemispheres, spinal cord, and meninges; and non-parenchymal, which involves CVST and arterial problems.

What Are the Clinical Manifestations of Neuro-Behcet’s Disease?

Neuro-Behcet's disease (NBD) presents with clinical manifestations categorized into central nervous system (CNS) and peripheral nervous system (PNS) symptoms. CNS manifestations can be further divided into parenchymal and non-parenchymal subtypes.

1. The parenchymal subtype is more common and includes brainstem, hemispheric, spinal, and meningoencephalitis syndromes.

2. The non-parenchymal subtype involves cerebral venous sinus thrombosis (CVST) and arterial involvement.

3. Instances with both parenchymal and non-parenchymal involvement are rare.

Common symptoms of neuro-Behcet's disease include:

• Headaches: Persistent and severe headaches are a frequent symptom of NBD. These headaches may be localized or diffuse and are often accompanied by other neurological signs.

• Meningitis: Inflammation of the meninges, the protective membranes enveloping the brain and spinal cord, can lead to symptoms such as neck stiffness, sensitivity to light (photophobia), and fever.

• Cognitive and Behavioral Changes: Neuro-Behçet's disease can cause cognitive impairment, memory problems, and changes in behavior and mood. Patients may experience difficulties in concentration, attention, and decision-making.

• Motor Weakness: NBD can lead to muscle weakness, making it challenging for individuals to perform everyday tasks or walk.

• Sensory Disturbances: Sensory deficits, such as numbness, tingling sensations, or loss of sensation, may occur in the limbs or other parts of the body.

• Cranial Nerve Involvement: Inflammation of the cranial nerves can result in various neurological deficits, such as facial weakness, double vision (diplopia), or difficulty swallowing.

• Ataxia: This condition denotes an absence of coordination and balance, leading to unsteady movements and difficulty walking.

• Seizures: Some individuals with NBD may experience seizures, which can range from mild to severe.

• Spinal Cord Involvement: Inflammation of the spinal cord may lead to weakness or paralysis of the limbs, sensory disturbances, and problems with bowel and bladder control.

• Psychiatric Symptoms: Neuro-Behcet's disease can cause psychiatric symptoms, including depression, anxiety, and psychosis.

• Visual Disturbances: Inflammation of the optic nerve or retina may result in visual disturbances, including blurred vision, eye pain, or vision loss.

How Can Neuro-Behcet’s Disease Be Diagnosed?

The diagnostic process usually initiates by gathering a detailed medical history, focusing on any previous or current symptoms of Behcet's disease (BD) and any other medical conditions. The physician will conduct a physical examination, looking for signs of neurological involvement, such as cranial nerve abnormalities, motor weakness, and sensory deficits. A specialized neurological evaluation will be conducted to assess the patient's cognitive function, coordination, reflexes, and other neurological functions. The presence of specific neurological symptoms can provide essential clues for diagnosis. There are specific diagnostic criteria for NBD, which are used to guide the diagnosis. These criteria consider various clinical features and laboratory findings and help to differentiate NBD from other neurological disorders. The other diagnostic steps are listed below:

• Imaging Studies: Magnetic resonance imaging (MRI) of the brain and spinal cord serves as a valuable method for identifying inflammation, lesions, or abnormalities in the central nervous system. MRI findings, along with clinical symptoms, can help support the diagnosis of NBD.

• Cerebrospinal Fluid (CSF) Analysis: A lumbar puncture (spinal tap) is performed to obtain a sample of CSF (cerebrospinal fluid) surrounding the brain and spinal cord. CSF analysis can reveal elevated white blood cell count (pleocytosis), increased protein levels, and other abnormalities indicative of central nervous system inflammation.

• Genetic Testing: Although not a diagnostic criterion, genetic testing for specific HLA (human leukocyte antigens) alleles, such as HLA-B51, can provide supportive evidence for a diagnosis of NBD, as these alleles are more prevalent in affected individuals.

• Exclusion of Other Conditions: It is essential to eliminate other causes of neurological symptoms, such as multiple sclerosis (a chronic autoimmune disease affecting the central nervous system), central nervous system vasculitis (inflammation of blood vessels within the central nervous system), infections, and other inflammatory or autoimmune disorders.

Since NBD is a multisystem disorder, the patient may need evaluation by various specialists, including neurologists, rheumatologists, ophthalmologists, and dermatologists. Collaboration among these experts is crucial for a comprehensive assessment and accurate diagnosis. Neuro-Behcet's disease can be a progressive condition with recurrent flares and remissions. Regular follow-up visits and monitoring are essential to assess disease activity, respond to treatment, and manage any complications that may arise.

What Is the Treatment for Neuro-Behcet’s Disease?

The treatment options for neuro-Behcet's disease include the following:

1. Corticosteroids: During acute flares of NBD, high-dose corticosteroids, such as Prednisone, are often prescribed to rapidly reduce inflammation and control symptoms. These medications are usually given for a short period to manage disease activity.

2. Immunosuppressive Medications: To control the abnormal immune response underlying NBD, immunosuppressive drugs may be used. Azathioprine, Methotrexate, Mycophenolate mofetil, and Cyclosporine are some of the commonly used immunosuppressive agents. These medications help in reducing the frequency and severity of disease flares.

3. Biologic Agents: In more severe cases of NBD that do not respond well to conventional treatments, biologic agents may be considered. Tumor necrosis factor (TNF) inhibitors, such as Infliximab or Adalimumab, can target specific inflammatory pathways and provide additional control over the disease.

4. Symptomatic Treatment: Depending on the specific neurological symptoms experienced by the patient, symptomatic treatment may be employed. Anticonvulsants are used to manage seizures, pain relievers for headaches, and medications for managing psychiatric symptoms or depression.

5. Intravenous Immunoglobulins (IVIG): In some cases, intravenous immunoglobulins might be given to modulate the immune response and reduce inflammation.

6. Plasma Exchange: Plasma exchange (plasmapheresis) is a treatment that involves removing a patient's blood plasma and replacing it with donor plasma. This method can be beneficial in certain severe cases of NBD to remove inflammatory substances from the bloodstream.

7. Rehabilitation and Supportive Care: Patients with NBD may require physical and occupational therapy to manage motor weaknesses and ataxia and improve overall function. Supportive care, including psychological support, can also be essential in coping with the emotional and mental challenges of living with a chronic neurological condition.

Conclusion:

Neuro-Behcet's disease has a very variable prognosis that depends on a number of different factors. The overall prognosis can be significantly impacted by early diagnosis, appropriate treatment, regular follow-up, and a comprehensive approach to managing the disease. If a patient shows unclear neurological problems and MRI (magnetic resonance imaging) reveals medium-sized lesions in the brainstem or basal ganglia, doctors should think about the possibility of neuro-Behcet's disease (NBD). In such cases, a thorough examination of the mouth, genitals, eyes, and skin, along with a history of systemic symptoms, should be conducted to investigate the potential presence of NBD, especially if the patient has not been diagnosed with Behcet's disease before.