What significance does skin lesions have for the diagnosis of neurological diseases ?
The latest clinical reasoning series of Neurology magazine reports a case of a 68-year-old man who developed palmar rash, leg pain and inability to walk. Let’s take a look at the clinical reasoning process.
translation: reflection without trace
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Part 1
The patient is a 68-year-old man who presented with "leg pain and weakness for 3 weeks". I used to be very active and walked 3-4 miles every day. Three weeks before treatment, the patient developed diffuse lower limb muscle and joint pain; in the following three days, his pain developed into obvious burning and pain in both legs, which affected his sleep. Two weeks after onset of illness, he presented to a local emergency room complaining of this pain. Hip X-rays and ultrasound were unremarkable, and he was discharged on 20 mg prednisone daily. However, the pain persisted and he developed new weakness in his legs. The patient began using crutches within 3 weeks, fell while walking on the street, and was subsequently unable to stand, resulting in hospitalization. There were no obvious abnormalities in bowel or bladder function. He had a past medical history of coronary artery disease, type 2 diabetes, hypertension, and hyperlipidemia.
Physical examination showed that the mental status and cranial nerves were normal. Motor examination showed that the bulbar muscle, deltoid muscle , biceps, triceps and gastrocnemius muscle strength were normal, but the following muscles had varying degrees of weakness (right/left): abductor pollicis brevis (4/4) , the first dorsal interosseous muscle (4/4), the abductor of the little finger (4/4), the finger extensor (4/4), the hip flexor (3+/3), the hip abductor ( 3+/3), knee flexors (4/3+), knee extensors (4/4), tibialis anterior (4/3), tibialis posterior (4/4) and peroneus longus Muscle and Muscle brevis (4+/4). The proprioception and vibration sense in the toes and ankles were lost bilaterally, but there was sensory impairment in the sellle area and and sensory planes. The arm tendon reflexes were 2+, but the knee and ankle reflexes were not elicited, and the bilateral plantar pathological signs were not elicited. It has a wide gait with small and cautious strides, requiring the assistance of 2 people. Post-voiding bladder examination showed no obvious abnormalities.
question thinking:
1. Positioning diagnosis?
2. What are the differential diagnoses?
Part 2
This patient's progressive pain, weakness, and sensory loss involving multiple myotomes ; diminished reflexes and lack of signs of myelopathy consider polyradiculopathy as the most likely possibility, involving C8-T1 and diffuse Sexual lumbosacral level. Polyradiculopathy has many causes and can be divided into structural and nonstructural categories. Structural causes include acquired spinal stenosis caused by ankylosing spondylitis, degenerative disc disease, primary tumors, leptomeningeal metastases, and tethered cord syndrome leading to nerve root compression. However, given the pattern of weakness at the C8-T1 and diffuse lumbosacral levels, the absence of localized pain and patchy involvement of the upper and lower extremities make these less likely. Nonstructural causes include infections, inflammatory diseases, metabolic pathologies, and neurolymphomatosis. Infectious causes are most important to consider and include syphilis, Lyme disease, tuberculosis, varicella-zoster virus, HIV, and cytomegalovirus. Inflammatory diseases include neurosarcoidosis and acute and chronic inflammatory demyelinating polyneuropathies. It reaches the peak within three weeks, which seems a bit slow for AIDP; the development of limb weakness and seems a bit fast for typical CIDP (generally progresses over eight weeks). Given his diabetes stability, upper extremity involvement, and symmetrical pain and weakness, diabetic amyotrophy is less likely. The absence of systemic symptoms or changes in bowel/bladder habits makes neurolymphomatosis unlikely.
In general, pain is not usually a prominent feature of most polyradiculopathies, but if present, it may indicate a compressive, infectious, infiltrative, or inflammatory lesion.
Therefore, risk factors for immunocompromised status should be carefully examined, including history of sexually transmitted diseases, possible infectious exposure, malignant status, and medications. Finally, other neuromuscular disorders should also be considered, including myopathy, neuromuscular junction disease, and motor neuron disease.
Additional medical history revealed that the patient had multiple male partners, no protection, and no history of tick exposure. The patient did not recall whether he had chancre, erythema migrans, or other rashes. However, dermatological examination revealed a small, non-tender, round, red macular rash on the palms and soles of the patient's feet (Figure 1-A).
Magnetic resonance imaging (MRI) of the lumbosacral spine at the local hospital showed smooth enhancement of the cauda equina nerve root without spinal cord signal changes (Figure 1-B/C/D).
Figure 1 Patient’s palm image and spinal cord MRI examination. A: Palm rash. B-D: MRI examination shows enhancement of the cauda equina nerve root without spinal cord signal changes.
question thinking:
1. What additional checks are needed?
2. How to treat?
Part Three
Preliminary laboratory test results showed positive Lyme and syphilis antibody screening tests, with no other obvious abnormalities, hemoglobin A1c was 7.4%; biochemical panel, TSH, ANA, creatine kinase/ aldolase, SPEP, HIV screening and viral load, gonorrhea-chlamydia nucleic acid testing, SARS-CoV-2 PCR and blood culture showed no obvious abnormalities. Given the high suspicion of secondary syphilis with polyradiculitis, the patient underwent lumbar puncture. Cerebrospinal fluid (CSF) examination showed an initial pressure of 12cm H2O and mixed pleocytosis (80 nucleated cells/mm3, including 7 red cells /mm3, neutrophils 36%, lymphocytes 30% and mononuclear cells Cell 18%), protein elevated (127.2mg/dL) and glucose 139mg/dL (serum glucose 168mg/dL).
Based on this CSF signature, the patient was started on empiric intravenous ceftriaxone. About 6 hours after starting antibiotics, the patient became comatose, his blood pressure dropped to 60/40mmHg, and he was afebrile. A diffuse rash appears on the abdomen. The patient received 100 mg of intravenous hydrocortisone, and the rash and hypotension improved rapidly. Given the high likelihood of treponemal infection, the patient's response should be considered Jerisch-Herxheimer reaction (JHR).
Subsequent Treponema pallidum particle agglutination and rapid plasma reagin (RPR, 1:32) returns were positive; the cerebrospinal fluid Venereal Disease Research Laboratory (VDRL) test was also positive (1:1). serum Lyme immunoblot (WB) shows 1/10 IgG bands, but CSF Lyme IgG B shows 5/10 IgG bands.
Questions to think about:
1. How to interpret syphilis and Lyme test results?
2. Is it necessary to adjust the treatment?
Part 4
In this patient, the diagnosis of syphilis is based on the history, rash, and a positive Treponema pallidum/non-Treponemal pallidum test. Additionally, the diagnosis of neurosyphilis is based on neurological findings, pleocytosis, elevated protein levels, and VDRL+. CSFVDRL is highly specific, with a positive predictive value of 100% unless contaminated by blood.
However, diagnosing Lyme disease is not straightforward and it is recommended to follow a standard diagnostic process. The patient's initial serum LymeWB had only one IgG band (41 kD) and was IgM negative, which did not support a definite diagnosis of Lyme disease, but could not rule out early disseminated infection. And its CSFLymeWB showed five bands (93/58/41/39/23kDa). Generally speaking, it is rare to have negative serology but positive CSF. Although antibodies against Treponema pallidum can cross-react with certain B. burgdorferi antibodies, it is highly unlikely that they will cross-react with five B. burgdorferi-derived antigens simultaneously. Infectious Disease Society of America (IDSA) guidelines recommend testing the CSF:serum antibody index to demonstrate that CSF antibodies are produced directly from intrathecally and not from the serum. Due to special reasons, the CSF and serum samples in this case were sent to two different laboratories, so the index could not be calculated. However, five positive CSFIgG bands and one serum IgG band still strongly support high levels of intrathecal B. burgdorferi-specific IgG synthesis.
According to CDC recommendations, the first-line option for neurosyphilis is intravenous injection of penicillin G. Two studies have shown that intravenous ceftriaxone has similar efficacy to penicillin , so CDC guidelines recommend ceftriaxone as an alternative therapy.According to the recent IDSA, intravenous ceftriaxone and oral doxycycline are the mainstay treatments for neuroborreliosis, with intravenous penicillin as an alternative. For this case, we chose to use intravenous penicillin to target neurosyphilis and oral doxycycline to target neuroborrelia. Patient
experienced neurological improvement after completing 14 days of penicillin and 28 days of oral doxycycline. Common practice is to repeat CSF examinations every 6 months after completing treatment to determine treatment response, because if CSF pleocytosis does not decrease within 6 months or CSF abnormalities do not normalize within two years, the patient may need to be re-treated. However, increasing evidence suggests that a ≥4-fold decrease in RPR after treatment strongly indicates CSF normalization. Six months later, the patient's CSF follow-up showed decreased protein (72 mg/dL), resolution of pleocytosis, and negative VDRL, but a serum RPR titer of 1:32. One year later, the patient had unclean sexual contact again, and the serum RPR titer returned to 1:256. The number of cells and protein in and cerebrospinal fluid increased, suggesting reinfection with syphilis. The patient received another course of penicillin, with improvement in RPR and CSF.
Original text index: JosephYoungHunYoon,JacquelineMadeleineSolomon,YijiaLi,etal.ClinicalReasoning:A68-YearOldManWithPalmarRash,LegPain,andInabilitytoWalk.NeurologypublishedonlineJune15,2022.DOI10.1212/WNL.0000000000200933
