Neurosyphilis manifesting as lightning pain

ARTICLE

Auteur(s) : Shanying Mao, Zhirong Liu

Department of Neurology, Second Affiliated Hospital, College of Medicine, Zhejiang, University, 88 Jiefang Road, Hangzhou China. 310009

accepté le 30 Mars 2009

Neurologic complications can occur during the early and late stages of syphilis, the spectrum of which includes meningitis, stroke, myelopathy, cranial nerve involvement, demyelination symptoms, seizures, and headaches, all of which can be confused with many distinct neurological diagnoses. Such manifestations may be involved at any stage of syphilis infection in about 5-10% of untreated patients. Neurosyphilis is classified into four syndromes, including syphilitic meningitis, meningovascular syphilis, parenchymatous, and gummatous neurosyphilis [1-3]. Since the beginning of the antibiotic era, the widespread and somewhat indiscriminate use of antibiotics in recent years has altered the clinical presentation patterns of neurosyphilis considerably, leading to complex and inaccurate diagnosis and treatment of this disease [4-9]. A high index of suspicion and clinician awareness is thus crucial to recognize and diagnose neurosyphilis properly [10].

In this report we describe three patients who initially presented with intermittent chronic lightning-like pains in the limbs that persisted over several years. These patients were subsequently diagnosed during their clinical evaluations as having neurosyphilis.

Case reports

Case 1

Nine months previously, the patient had begun experiencing bilateral numbness in the lower extremities that spread gradually from the toes to the groin over the course of 5 months, with decreasing but unbearable pain intensity. Concurrently, the patient had difficulty maintaining his balance while walking, and falling incidences were becoming more frequent. Additionally, when the patient walked on hard ground, he described the feeling of walking on a “cotton pile”. He did not exhibit signs of paralysis, dysuria, or bowel difficulties. He had more than one sexual partner, and admitted engaging in sexual activities with prostitutes 10 years prior to this time. A family history included paternal death from schistosomial cirrhosis, a living healthy mother, and one sister with Sjögren’s syndrome. The remaining living relatives were in good health.

Upon examination, we found that his temperature, pulse, breath, and blood pressure were normal. The patient was alert, without rash or skin ulceration. The lungs were clear, and neither heart murmur nor cardiomegaly was noticed. The patient did not have lymphadenectasis or hepatosplenomegaly. His left and right pupils were 3 mm and 2.5 mm in diameter, respectively, presenting with irregular outlines. The direct and consensual light reflexes were absent, and the convergence reflex was normal (Argyll-Robertson pupil). The optic discs were clear, and papilledema was not evident. On palpation, the neck was found to be supple, however, sensory responses to touch, temperature, and pinprick were lost below the L1 level, and there was loss of proprioception and vibration in the lower extremities. His strength was found to be 5/5 throughout all muscle groups. The tendon reflexes were grade 2/4 bilaterally at the biceps and triceps, and grade 0/4 bilaterally at the ankle and patellar. The plantar responses were bilaterally flexor. His mini-mental state examination score (MMSE) was 29 out of 30.The laboratory tests, including complete blood cell (CBC) panel, routine urine and stool analyses, fasting blood glucose, and oral glucose tolerance tests (OGTT) were normal. Additionally, the erythrocyte sedimentation rate (ESR), and antinuclear antibody tests were normal. His serum folic acid and vitamin B₁₂ levels were in the normal range. Nothing abnormal was found during the electromyography and nerve transduction tests, and his human immunodeficiency virus (HIV) antibody test (ELISA test) was negative. The cerebrospinal fluid (CFS) test showed normal erythrocyte and leukocyte counts along with normal glucose and chloride levels, but indicated elevated protein (56.5 mg/dL) levels and an IgG index of 0.56. A treponema pallidum particle agglutination assay (TPPA) was positive in the CSF. A rapid plasma reagin (RPR) was positive at a titer of 1:8, and there was no evidence of tumor. A serum treponema pallidum particle agglutination assay (TPPA) was positive and the serum RPR titer was 1:64.

Based on our test results, we ascertained a diagnosis of tabes dorsalis. The patient was treated with crystalline penicillin G, 4 million units intravenously every 4 h for 14 days, followed by weekly intramuscular injections of 2.4 million units benzathine penicillin for 3 weeks. On the follow-up examination 6 months later, the patient’s pain level was mildly improved, as did his CBC and CSF examinations, and his serum and CSF RPRs for syphilis were 1:16 titer and 1: 4 titer, respectively.

Case 2

A neurological examination showed Argyll-Robertson pupil (figure 1), with the right pupil dilated to 3 mm in diameter with an irregular outline, while her her left pupil was 2 mm in diameter with a rounded outline. Her direct and consensual light reflex was negative, with a visible convergence reflex. The patient was alert and talked distinctly, and her MMSE was 30 out of 30. Her strength was 5/5 throughout all muscle groups with muscular tension, as well as normal sensations to touch, temperature, pinprick, and vibration. Her plantar responses were bilaterally flexor, and her Romberg’s sign was negative.

The CBC panel, hepatic and renal function tests, and serum electrolytes were normal. The OGTT, serum folic acid, and vitamin B₁₂ levels were also in the normal ranges, while the antinuclear antibody test was negative. Her serum TPPA was positive and the RPR titer was 1:16, and her serum HIV antibody test was negative. The CSF pressure was 150 mm H₂O, with elevated protein levels (72 mg/dL), and 18 leukocytes; the CSF TPPA was positive, and the RPR titer was 1:8. The glucose and chloride levels were normal, however, the IgG index rose to 0.75. A cranial MRI was normal, while a lumber spinal MRI showed a slight herniation in the L5/S1 intervertebral space. Ultimately, we diagnosed this patient with neurosyphilis. The patient was treated with crystalline penicillin G, 4 million units intravenously every 4 h for 14 days, followed by weekly intramuscular injections of 2.4 million units benzathine penicillin for 3 weeks. At the follow-up examination 6 months later, her blood and CSF examination results had improved, and her RPR serum and CSF titers were 1:8 and 1:4, respectively. The patient reported a modest improvement in her pain.

Case 3

Upon neurological examination, we found the patient to be alert, talking distinctly and with a MMSE of 30 out of 30. The patient’s strength was determined to be 5/5 in all muscle groups, and his sensations to touch, temperature, pinprink, and vibration were normal. The Babinski and Romberg signs were negative. His CBC, serum electrolyte, hepatic and renal tests were all normal. The OGTT, serum vitamin B₁₂, and serum folic acid levels were also within normal ranges; the cranial and cervical spinal MRIs were also normal. The antinuclear antibody test was negative, while the serum TPPA and RPR results were positive, with a 1:8 RPR titer. The CSF was aspired with the pressure at 130 mm H₂O, and the protein level was 68 mg/dL. The glucose and chloride levels were normal, and the cell count test revealed 6 leukocytes; the CSF TPPA was positive, the RPR titer was 1:4, and the IgG index was 0.7.

This patient was diagnosed with neurosyphilis and was treated with crystalline penicillin G and benzathine penicillin following routine dosage requirements. At 3 months post-treatment with penicillin, the patient indicated a mild improvement in his pain during the follow-up examination. The results of his blood and CSF examinations had improved, and his serum and CSF RPRs for syphilis were both 1:4 titer, and the cell count and protein content levels were 0/mm³, 36 mg/dL respectively.

Discussion

The diagnosis of neurosyphilis, or more often the definite exclusion of neurosyphilis as a clinical possibility, remains a difficult problem. The classic forms of the disorder (general paresis, tabes dorsalis) are rarely seen in clinical practice, having been replaced by other atypical clinical forms, with fewer symptoms, in which the classical neurosyphilis signs are absent. The criteria for diagnosing neurosyphilis include central nervous system or ophthalmic signs or symptoms, as well as serologic evidence (positive nontreponemal and treponemal test results) for syphilis infection along with one of the following parameters: positive VDRL-CSF, increased CSF protein (> 40 mg/dL), or increased CSF WBC count (> 5 mononuclear cells/μL) [2]. A reactive CSF-venereal disease research laboratory (VDRL) test has long been considered to be sufficient to diagnose neurosyphilis, although false-positive results caused by serum contamination are possible [11]. According to Castro et al. [13] and our patient cases presented herein, RPR can be used as an alternative to the VDRL to diagnose neurosyphilis. We confirmed a neurosyphilis diagnosis from highly positive RPR serum and CSF titers, combined with clinical symptoms (lighting-like pains) and increased CSF protein levels, or an increased CSF WBC count. Otherwise, a serum analysis for syphilis (TPPA test and RPR) is considered routine in all patients who present with atypical clinical forms (restricted mainly to lighting-like pain) and who are in a high-risk population.

One of the significant clinical features that we observed in our patients was intermittent lightning limb pain, characterized by early onset, a lightning or stabbing sensation, predominant nocturnal occurrence, and unfixed location and duration. In all cases, the onset pain was described as long-lasting and lightning-like.

Because neurosyphilis is easy to misdiagnose, treatment delay is common. Thus, clinicians should recognize and pay adequate attention to the tell-tale symptoms, and include syphilis as a possible diagnosis during examination. Lightning-like pain is the prominent symptom accompanying tabes dorsalis. Neurosyphilis-induced tabes dorsalis is estimated to account for about one-third of all neurosyphilis cases. Generally, in tabes dorsalis, the onset of symptoms occurs slowly in untreated patients between fifty to sixty years of age. During disease development, the symptoms become progressive and largely irreversible. If neurosyphilis is treated early, however, the accompanying symptoms may resolve [2]. The presently reported cases were unlike some previously reported cases [1], in that the neuroimaging test results were normal. In conclusion, our experience with neurosyphilis indicates that clinicians should become familiar with and able to recognize the complex presentation of symptoms that can occur with neurosyphilis.

Acknowledgements

References

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