ABSTRACT
Brucellosis is a zoonotic infection that affects 500,000 individuals each year worldwide. Neurological complications occur in up to 5% of cases, and ocular involvement is rare. This report describes the case of a 26-year-old woman with progressive lower limb weakness and significant ambulatory impairment following two months of headache, nausea, vomiting, and visual disturbances. The patient had a history of urinary incontinence, lower back pain, and raw goat milk consumption. Clinical examination revealed bilateral papilledema and muscle weakness. Positive Brucella culture, abnormalities in the cerebrospinal fluid, and magnetic resonance imaging findings confirmed the presence of neurobrucellosis. Treatment with antibiotics led to minimal initial improvement. However, significant recovery was observed five months post treatment initiation. This case highlights the importance of considering neurobrucellosis in endemic regions and underscores its distinct clinical and radiological features. Early recognition and treatment are crucial for reducing morbidity.
Brucellosis, often referred to as Malta fever, undulant fever, or Mediterranean fever is a systemic infectious disease caused by Brucella bacteria. It is primarily transmitted to humans through the consumption of unpasteurized or raw milk and cheese from milk of infected animals such as sheep, cattle, camels, pigs, or dogs. Additionally, direct contact with infected animals can lead to transmission. In laboratory settings, brucellosis is recognized as one of the most prevalent infectious diseases transmitted to humans, typically occurring when laboratory personnel inadvertently inhale the bacteria.1
Brucellosis is a zoonotic disease that infects over 500,000 individuals worldwide each year.2 The disease poses significant challenges to economic, agricultural, and public health sectors due to its impact on both human and animal populations. It is predominantly found in developing countries and is rare in industrialized nations. With the increasing ease of global travel and trade, the risk of brucellosis spreading internationally is growing. This risk is particularly notable in countries such as Saudi Arabia, which encompasses substantial traveler and livestock movement. In the absence of stringent disease prevention protocols, any nation is vulnerable to the threat of brucellosis. In Saudi Arabia, brucellosis continues to be a significant health concern, underscoring the importance of effective control measures.1
Brucellosis incidence in Saudi Arabia has been extensively assessed over various periods. In 2004, the incidence rate was recorded at its highest, with 22.9 cases per 100,000 population and a total of 5,169 reported cases, marking it the peak year for the disease. Over the subsequent years, a declining trend in incidence was noted, with the lowest rate recorded in 2012 at 12.5 cases per 100,000 population. Additionally, the regions of Al-Qassim, Aseer, and Hail consistently reported the highest incidence rates, often exceeding 22 cases per 100,000 population.3
Neurobrucellosis is an infection affecting the nervous system, accounting for approximately 5% of all brucellosis cases.4 Despite antibiotic treatment, this condition may culminate in severe complications such as sepsis, shock, and multiple organ failure, with a mortality rate of up to 5.5%. Frequent underdiagnosis or misdiagnosis is a significant challenge in managing neurobrucellosis, primarily due to the non-specific and varied clinical manifestations. These manifestations include meningitis; meningoencephalitis; encephalitis; polyneuropathy; subarachnoid hemorrhage; radiculitis; myelitis; motor and cranial nerve deficits; sciatica; confusion; psychological disturbances; and seizures.5,6
There is a need for heightened awareness and a more comprehensive understanding of the atypical presentations of brucellosis among healthcare professionals, particularly in regions where brucellosis is endemic. This report presents a case of neurobrucellosis with atypical clinical symptoms in a patient admitted to our medical facility. Describing this case in details, we aim to provide insight into the diagnostic challenges and critical need for timely and accurate identification of neurobrucellosis. This would help in bridging the gap in clinical knowledge and improve patient outcomes through early intervention and appropriate treatment strategies.
Case Report
Patient information
A 26-year-old female patient presented to our emergency department with a five-day history of progressive symmetrical weakness in her lower limbs. She reported weakness that began in the proximal muscles, which led to difficulty climbing stairs and rising from a sitting position. Over a few days, the weakness progressed to involve the distal muscles, eventually necessitating walking assistance by the fifth day. The onset of her current condition dates back to 2 months and was marked by bitemporal pressure-like headaches, along with nausea, non-projectile vomiting, and blurry vision associated with lacrimation that was more pronounced in the right eye. Despite being evaluated in the emergency room and asked to undergo further diagnostic workup, the patient refused admission and was subsequently discharged (2 weeks before current admission). Although the patient had a history of urinary incontinence and lower back pain, she denied experiencing fever; sweating; weight loss; sensory or bulbar symptoms; upper limb weakness; or facial weakness. She also mentioned a history of consuming raw goat milk.
Clinical findings
The patient experienced fatigue and was alert and oriented. Cranial nerve examination revealed no abnormalities, except for bilateral papilledema. Upper limb motor function, coordination, and sensory examination results were unremarkable. In the lower limbs, power was affected in a symmetrical pattern. Hip extension, flexion, abduction, and adduction were 2/5. The knee and ankle dorsiflexion angles were 3/5°. The plantar flexion showed a score of 4/5. Deep tendon reflexes showed absence of knee reflex, +1 ankle reflex, and +2 in the upper limbs. Equivocal plantar responses were observed bilaterally. Normal muscle bulk and tone was observed all over without fasciculation. Sensations were intact bilaterally. No scapular winging, percussion, or grip myotonia were observed. No high arches or hammer toes were observed. Gait and station could not be assessed because the patient could not stand or walk.
Timeline
The patient’s care and treatment history were meticulously documented, highlighting key events and interventions. These events are chronologically organized in a detailed timeline to provide a clear visual representation of progress in the patient’s condition (Table 1).
- Historical and current information from the episode of care organized as a timeline.
Diagnostic assessment
The patient showed a highly positive Brucella abortus screening titer of 1:320 by the enzyme-linked immunosorbent assay (ELISA) (immunoglobulin [Ig]M 0.49 ratio [negative <0.8 ratio], and IgG 2.72 ratio [positive ≥1.1 ratio]. A lumbar puncture (LP) was performed, revealing a normal opening pressure but abnormalities in the cerebrospinal fluid (CSF): white blood cells (WBC; 300), lymphocytes (97%), protein level (487 mg/dL) (normal range: 15-45 mg/dL), and glucose levels (3 mmol/L) (normal range: 2.3–4.1 mmol/L). Blood culture was positive for Brucella melitensis, whereas CSF culture was negative. Biochemistry analysis, including complete blood count, creatine kinase level, and hormonal profile revealed values within normal range.
Nerve conduction studies (NCS) were performed upon admission and repeated 10 days later. The results, as presented in Tables 2& 3, showed no electrodiagnostic evidence of large-fiber neuropathy. Nerve conduction studies (NCS) were performed on admission and 10 days later; there was no electrodiagnostic evidence of large-fiber neuropathy. As presented in Tables 2&3.
- Motor Nerve Conduction Study.
- Sensory nerve conduction study.
Nonenhanced magnetic resonance imaging (MRI) of the brain revealed normal findings. Enhanced MRI of the lumbosacral plexus showed abnormal diffuse enhancement of the lumbar intradural nerve root in the cauda equina as shown in Pictures figures 1a and 12b, without vertebral body or disc enhancement and epidural or paraspinal collection.
- Enhanced MRI of the lumbosacral plexus showing abnormal diffuse enhancement of the lumbar intradural nerve root in the cauda equina, with no vertebral body or disc enhancement, and no epidural or paraspinal collection.
Therapeutic intervention
Based on the initial CSF culture results, administration of the anti-meningitis drug, ceftriaxone, was started at a dosage of 2 g intravenously (IV) twice daily (BID); vancomycin, 1 g BID; and, acyclovir 750 mg, IV three times a day (TID).
The patient was suspected of having brucellosis (which was confirmed later by blood screening and blood culture); Infectious Diseases were consulted, and gentamicin administration was initiated at 200 mg IV once a day (OD), rifampicin, 600 mg orally (PO) OD; and, Bactrim, 160 mg IV TID; acyclovir and vancomycin administration were withheld.
After 10 days, gentamicin administration was stopped, and doxycycline administration at 100 mg PO BID was initiated.
Ceftriaxone administration was planned for 4 weeks as the patient refused CSF analysis/culture follow-up.
After 17 days, rifampicin was switched to ciprofloxacin (500 mg PO BID) because of an increase in liver enzymes.
After 3 weeks, the patient signed a discharge against medical advice form, and she was discharged on doxycycline (100 mg PO BID) and ciprofloxacin (500 mg PO BID) for 60 days.
During a three-week hospitalization with antibiotic management and physiotherapy, the patient showed improvement in headache and eye symptoms, but the weakness persisted.
Follow-up and outcomes
The patient was discharged with a referral to the physiotherapy department (2 sessions per week) and prescription of a home exercise program. At the 60-day physiotherapy follow-up, there was improvement in the patient’s back and abdominal muscles. By day 90, the patient started walking short distances, and by day 120, a dramatic positive change in the physical abilities was observed. However, the patient reported that difficulty in climbing stairs persisted.
Discussion
Neurobrucellosis is an infection affecting the nervous system, accounting for approximately 5% of all brucellosis cases.4 A study involving 82 patients with neurobrucellosis revealed that the most frequent manifestation was peripheral nervous system involvement in 34 patients (41.46%). This was followed by meningitis in 28 patients (34.14%), cranial nerve damage in 20 (24.39%), and meningoencephalitis in 10 (12.2%). Additionally, three patients had transverse myelitis; one experienced a stroke. The most commonly affected cranial nerve was the vestibulocochlear nerve, in 12 patients (14.63%), followed by the facial nerve in 7 (8.53%), and the optic nerve in 1 (1.22%). Among these 82 patients with neurobrucellosis, symptoms included meningeal irritation and headache in 84.1% and fever, nausea, vomiting, and positive meningeal signs in 83%. These symptoms were more prevalent compared with patients with brucellosis, where such symptoms occurred with lower incidence.5 Herein, the patient presented with progressive symmetrical weakness in her lower limbs, accompanied by bitemporal pressure-like headaches, nausea, non-projectile vomiting, and blurry vision with pronounced lacrimation in the right eye. Additionally, she had a history of urinary incontinence and lower back pain. These symptoms suggest a multifaceted involvement of both central and peripheral nervous systems, underscoring the commonality of these manifestations of neurobrucellosis. Although our patient did not exhibit specific cranial nerve damage, the presence of bilateral papilledema could indicate central nervous system involvement similar to that observed in the study. The correlation between the study and our case highlights the importance of thorough clinical examination and high clinical suspicion.
Neurobrucellosis can be diagnosed by fulfilling specific diagnostic criteria as outlined in various studies. In one approach, the criteria were: the presence of neurological symptoms and signs that could not be explained by other diseases, positive agglutination titer for Brucella in blood greater than 1:160, presence of pleocytosis in the CSF if patient received no treatment, and notable clinical improvement following appropriate therapy.7 Another approach for diagnosing neurobrucellosis among patients with laboratory-confirmed brucellosis involves the presence of at least one of the following criteria: symptoms and signs suggestive of neurobrucellosis, isolation of Brucella species from CSF and/or the presence of anti-Brucella antibodies in the CSF, evidence of lymphocytosis, increased protein levels, and decreased glucose levels in the CSF, or abnormal findings on cranial MRI or computed tomography (CT).8 In our case, the patient met several diagnostic criteria for neurobrucellosis. Her findings showed a highly positive Brucella abortus screening titer by ELISA and a high IgG ratio. CSF analysis revealed a high WBC count with lymphocytosis, a high protein level, and a normal glucose level. Blood culture was positive for Brucella melitensis, whereas the CSF culture was negative. These findings closely align with the diagnostic criteria outlined in both approaches. Non-enhanced MRI of the brain revealed normal findings, which is consistent with some cases of neurobrucellosis where cranial MRI does not show abnormalities. Highlighting that no contrast was used in the MRI of our case is important, which may influence the detection of abnormalities. However, enhanced MRI of the lumbosacral plexus showed abnormal diffuse enhancement of the lumbar intradural nerve roots in the cauda equina. The correlation between our case and the referenced diagnostic criteria underscores the complexity of diagnosing neurobrucellosis and highlights the importance of comprehensive diagnostic workups. This includes serological tests, CSF analysis, and advanced imaging techniques to ensure accurate diagnosis and appropriate treatment.
The pathogenesis of the disease involves both immunological mechanisms and direct invasion, leading to the demyelination of the white matter, spinal cord, and peripheral nerves of the brain. This results in various peripheral manifestations such as myelopathy, radiculopathy, or polyradiculopathy, which typically affect the legs more than the hands.9 The clinical manifestation in our case aligns with these findings, as our patient exhibited progressive symmetrical weakness in the lower limbs. Additionally, the NCS did not indicate signs of large-fiber neuropathy, which could be attributed to the unavailability of electromyography at the time of evaluation. This limitation underscores the necessity for alternative diagnostic approaches. Consequently, the identification of root enhancement in MRI findings becomes particularly critical. In our patient, MRI revealed abnormal diffuse enhancement of the lumbar intradural nerve roots in the cauda equina. This finding is indicative of inflammation or infection of the nerve roots, which could correlate with the pathophysiological process of demyelination seen in neurobrucellosis.
The ocular complications of brucellosis are infrequent, with uveitis being the predominant condition. Other potential ocular manifestations include keratoconjunctivitis, corneal ulceration, iridocyclitis, nummular keratitis, choroiditis, optic neuritis, papilledema, and endophthalmitis.10 These complications can pose diagnostic challenges, particularly in distinguishing between papilledema secondary to meningitis and that secondary to axonal loss and demyelination. The presence of bilateral papilledema in our patient necessitated a thorough differential diagnosis to ascertain the underlying cause. Although meningitis may cause papilledema due to increased intracranial pressure, demyelination associated with neurobrucellosis can also lead to optic nerve involvement, resulting in similar manifestations. In our case, the diagnostic challenge was further complicated by the absence of tools, such as visual evoked potentials, that could suggest axonal loss and demyelination.
This case report underscores the necessity of considering neurobrucellosis in patients with neurological symptoms and a relevant epidemiological history. Early diagnosis and appropriate antibiotic therapy are essential for favorable long-term outcomes despite initial management challenges.
However, this study has some limitations. First, as it is a single case study, the findings may not be generalizable because the unique characteristics and treatment response in this patient may not be representative of all neurobrucellosis cases. Additionally, the report may lack comprehensive clinical details and investigations, potentially affecting the understanding of disease progression and management.
Moreover, the documentation does not include detailed information on the patient’s adherence to the prescribed antibiotic regimen or other aspects of treatment compliance, which could significantly influence outcomes and recovery. The five-month follow-up period may be insufficient to capture all the long-term effects and potential complications. Long-term monitoring could provide more insights into the recovery trajectory and late-onset complications.
The interpretation of diagnostic tests, such as nerve conduction studies and imaging, can vary and be influenced by technical factors or individual expertise, potentially affecting the accuracy of the results. Future studies should address these limitations to enhance the robustness and applicability of these findings for neurobrucellosis management and outcomes.
In conclusion, despite its relatively rare occurrence, neurobrucellosis poses significant challenges owing to its diverse clinical manifestations and potential long-term complications. Early recognition of neurological symptoms can facilitate a prompt diagnosis and timely initiation of appropriate antibiotic therapy, leading to favorable long-term outcomes.
Patient Perspective
From the patient’s perspective, her main remaining issue after receiving treatment was difficulty in climbing stairs. Despite undergoing the prescribed treatments, she continued to face challenges with this particular activity, which significantly affected her daily life. She felt that addressing this issue was crucial for improving her overall quality of life and ability to perform everyday tasks independently.
Conclusion
Despite its relatively rare occurrence, neurobrucellosis poses significant challenges owing to its diverse clinical manifestations and potential long-term complications. Early recognition of neurological symptoms can facilitate a prompt diagnosis and timely initiation of appropriate antibiotic therapy, leading to favorable long-term outcomes.
Acknowledgment
We would like to extend our sincere gratitude to Editage (www.editage.com) for their professional assistance in English language editing, which significantly enhanced the clarity and quality of our manuscript.
Footnotes
Disclosure. The authors declare no conflicting interests, support or funding from any drug company.
- Received August 10, 2024.
- Accepted March 19, 2025.
- Copyright: © Neurosciences
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