Clinical Reasoning: A Young Woman With Rapidly Progressive Weakness and Paresthesia

Section 1

A 24-year-old Middle Eastern woman presented with a 2-month history of generalized weakness prominent in the left lower extremity. Her symptoms began with proximal left leg heaviness, progressing to both legs. Weakness was associated with gradually worsening paresthesia and reduced sensation in the left lower limb, originating from the hip down to the foot. She also had lip and bilateral numbness in the distal upper limbs and complained of a gradual-onset constant occipital headache with pain radiating to the neck, worsening in the supine position, and not relieved by oral analgesics. Headache was associated with photophobia, tinnitus, nausea, vomiting, and horizontal binocular diplopia, which was exacerbated when looking at far objects. The patient also experienced overflow urinary incontinence. She reported a significant weight loss of 13 kg but had no fever or night sweats.

Her medical history was significant only for brucellosis, diagnosed 2 years ago with persistent high-grade fever, chills, sweating, and diffuse myalgia after ingestion of unpasteurized milk. Family and social histories were unremarkable.

On examination, the patient was afebrile with normal blood pressure. The patient showed positive meningismus signs, including nuchal rigidity, Kernig sign, and jolt accentuation. Mental status and cognition remained intact. Cranial nerve examination revealed horizontal binocular diplopia with partially limited abduction of both eyes, impaired left facial sensation to pinprick and temperature, and right sensorineural hearing loss. The other cranial nerves were intact with normal fundi.

Motor examination revealed diffuse muscle wasting and decreased tone in the upper and lower extremities with no observable fasciculations. Her strength was 4/5 throughout the study period, except for the left lower extremity, which demonstrated foot drop and no antigravity strength. Reflexes were absent in the left biceps, brachioradialis, knee, and ankle. Hyporeflexia was observed on the right side. Plantar responses were flexor responses, and the Hoffman test result was negative.

Sensory examination revealed reduced sensation of light touch, temperature, and pinprick over the first 2 fingers and lateral forearm of the left upper limb along with the entire left lower limb. Vibration sensation was decreased in the left lower limb up to the knee level. The sensation of joint position in the toes was intact bilaterally. Systemic examination results were unremarkable, with no hepatosplenomegaly.

Section 2

The patient's symptoms were consistent with multifocal localization, including a lower motor neuron pattern and marked, asymmetric, generalized weakness in the left lower limb with left-sided areflexia, decreased tone, atrophy accompanied by sensory changes in the same limb, and overflow incontinence suggesting peripheral nervous system pathology, which potentially localized to the lumbar roots. Numbness of both arms and fingers, with dermatomal sensory loss, hyporeflexia, and a pattern of generalized weakness, indicated cervical polyradiculopathy. Perioral numbness with decreased left facial sensation suggested a lesion in the left trigeminal nerve involving the ophthalmic, maxillary, and mandibular branches, while hearing loss in the right ear suggested a lesion in the right vestibulocochlear nerve. Finally, occipital headache worsening in the supine position accompanied by photophobia, tinnitus, nausea, vomiting, and horizontal diplopia indicated increased intracranial pressure.

Polyradiculopathies along with cranial neuropathies suggested a multifocal leptomeningeal disease process, as these findings collectively localized to the brain and spinal cord meninges. Differential diagnoses of a subacute leptomeningeal process included bacterial and fungal infections, particularly tuberculosis and cryptococcosis, along with infections associated with raw milk ingestion and endemic infectious diseases of the Middle East such as brucellosis and listeriosis; neoplastic conditions such as leptomeningeal carcinomatosis and lymphoma; and rare inflammatory conditions such as sarcoidosis, IgG4, and histiocytosis.

Section 3

Laboratory tests revealed a normal leukocyte count of 4.8 × 10⁹/L (4.5–11.0 × 10⁹/L) with relative lymphocytosis of 67% (20%–45%). Metabolic panel results were within the normal range, with unremarkable C-reactive protein levels and erythrocyte sedimentation rate.

Blood and acid-fast bacillus cultures and serologic tests for Mycobacterium sp., various fungi, and Brucella sp. showed negative results. However, the serum agglutination test revealed high blood anti-Brucella antibody titer of 1:320.

The CSF opening pressure was high at 370 mmH₂O. The fluid was yellow and turbid. The protein level was markedly high at 138 mg/dL (15–45 mg/dL), whereas the glucose concentration, 24.84 mg/dL (40–69.3 mg/dL), was markedly lower than that in the serum. The erythrocyte count was unremarkable. Leukocyte count (80 leukocytes/μL) revealed lymphocytic pleocytosis (90% lymphocytes and 10% polymorphonuclear leukocytes). CSF cultures were negative for bacteria, fungi, and mycobacteria. The anti-Brucella antibody titer in the CSF was elevated to 1:80.

Brain MRI with contrast demonstrated multiple patchy subcortical, periventricular, and juxtacortical fluid-attenuated inversion recovery white matter hyperintensities with no postcontrast enhancement. It also demonstrated diffuse cranial nerve enhancement involving the bilateral oculomotor, trigeminal, abducens, and right vestibulocochlear nerves (Figure, A–C). Spinal cord MRI showed cauda equina nerve root enhancement (Figure, D).

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Figure MRI of the Brain and Lumbar Spine

(A) Axial fluid-attenuated inversion recovery MRI demonstrating multiple bilateral subcortical and periventricular white matter lesions. (B, C) Axial T1-weighted gadolinium-enhanced MRI showing smooth enhancement in the left abducens (yellow arrow) (B), right vestibulocochlear (blue arrow) (B), and left trigeminal nerves (C). (D) Sagittal T1-weighted gadolinium-enhanced MRI of the lumbar spine showing cauda equina nerve root enhancement.

Nerve conduction studies and needle electromyography showed normal sensory nerve action potentials and normal-to-low-normal compound muscle action potentials, with evidence of subacute-to-chronic cervical and lumbar radiculopathies. In view of the endemic regional origin, neurologic and constitutional manifestations, history of brucellosis and unpasteurized milk consumption, and CSF lymphocytosis with increased protein and decreased glucose levels, combined with high levels of anti-Brucella antibody titer, neurobrucellosis was the final diagnosis.

On further reviewing the patient’s brucellosis history from 2 years ago, she reported stopping her antibiotics independently after 1 month of treatment because of pregnancy and improvement in symptoms.

The patient was treated with a 1-month course of 2 g of intravenous ceftriaxone twice daily and a 4-month course of 600 mg of oral rifampicin and 100 mg of oral doxycycline. Her headache markedly improved, and diplopia resolved within a few days after her admission. The patient regained control of urination. However, she continued to experience abnormal sensations and generalized weakness, requiring her to rely on a wheelchair.

The patient's condition improved after completing the antibiotic therapy. At follow-up 8 months after treatment initiation, she could walk and function independently. She had minor residual deficits on examination, including mild lower limb weakness and right sensorineural hearing loss.