Neurosyphilis presenting with Guillain–Barre syndrome: a case report

The prevalence and incidence of syphilis in the United States has reached new highs since the 1940s, rising by 164% and 175% respectively between 2008 and 2018 [1, 2]. Typical manifestations of neurosyphilis can be divided into early and late stages, with the former encompassing meningitis and meningovasculitis, and the latter manifesting as tabes dorsalis and dementia paralytica [3]. Syphilis has also been associated with many atypical presentations including those that mimic idiopathic intracranial hypertension and Parkinson’s Disease [4]. It is thus increasingly important to recognize the myriad of clinical manifestations of syphilis due to the devastating sequelae if left undiagnosed and untreated. Here, we describe a case of neurosyphilis that presented with clinical Guillain–Barre Syndrome (GBS). While several case reports have described GBS-like symptoms in a patient with syphilis, this case is, to our knowledge, the first electrodiagnostically confirmed case of syphilitic GBS without coexisting confounders.

A previously healthy 37-year-old female presented to the emergency department with headache, rash, and bulbar weakness. Three months prior to admission (PTA), she gradually developed a constant, severe headache with photophobia. She presented to an urgent care clinic for these symptoms and was prescribed symptomatic medications without resolution. Two months PTA, she developed a pruritic rash on her chest, neck, palms, and soles. She again presented to urgent care and was given antihistamines for the rash. Two weeks PTA, she began to feel weakness in her arms as well as numbness in her arms, chest, and thighs. When her weakness progressed and she started to have difficulty swallowing, she came to the emergency department. She denied any fevers but reported intermittent chills for the past three months (Fig. 1).

In our case, the patient did have classic symptoms of neurosyphilis, including a headache and cranial neuropathies, as well as symptoms consistent with GBS. As she described a three month history of new headache, and since secondary syphilis typically occurs two to eight weeks after inoculation, we suspect that she developed neurosyphilis early into her infection [5]. It is often mistaken that neurosyphilis is a later stage of syphilis, when in fact inoculation of the central nervous system can occur within days of primary infection [3]. An estimated 25% of syphilis result in neurosyphilis and may progress in several stages. In the early stages, one may be asymptomatic with laboratory findings characterized by reactive serum and CSF VDRL tests. Meningovasculitis can present as well, resulting in strokes and meningomyelitis. If left untreated, the later stages of neurosyphilis consist of general paresis with progressive dementia (dementia paralytica) as well as tabes dorsalis. It has been postulated that the degree of CSF pleocytosis and hypoglycorrhachia is correlated with the severity of symptoms and stages, with an early stage of neurosyphilis associated with mild pleocytosis, acute meningeal neurosyphilis with significant pleocytosis and decreased glucose, and chronic disease associated with normal CSF findings [6‐9]. Wang et al. reported a median CSF WBC of 5.5 /mm3, with a range of (0–145.2 /mm3) in 103 patients with neurosyphilis [8]. Similarly, Pastuszczak et al. described a correlation of CSF pleocytosis and decreased CSF glucose with VDRL reactivity [9]. In this case, the minimal pleocytosis and normal glucose was unusual given the severity of her symptoms, but it is possible that the neurosyphilitic component of her presentation is in the earlier stages, and that GBS, which is not typically associated with significant pleocytosis or hypoglycorrhachia, may be the primary driver of her presenting symptoms.

Guillain–Barre syndrome (GBS) is an immune-mediated polyneuropathy that typically presents with a monophasic ascending pattern of sensory loss and weakness, initially in the hands and feet. In two-thirds of cases, there is an antecedent infection. Examination is notable for hypo- or areflexia, in addition to weakness and sensory loss, in a stocking glove distribution. While GBS commonly presents as a primarily demyelinating form, other variants have been described such as a motor-axonal neuropathy and Miller-Fisher syndrome, a primarily axonal neuropathy that presents with ophthalmoplegia, areflexia, and ataxia [10]. In this case, the nerve conduction testing demonstrated prolonged latencies in multiple motor nerves as well as absent F waves, consistent with demyelination. These nerve conduction findings overall support an acute inflammatory demyelinating polyradiculoneuropathy variant of GBS. It is important to note that cranial neuropathies have been described in syphilitic meningitis, though extremity involvement favors GBS [11].

There have been several studies describing GBS-like symptoms in a patient with syphilis. In 1998, Stepper et al. described a case of a 36-year-old man who presented with ataxia, diplopia, and a left cranial nerve VI palsy that improved with IVIG, but later relapsed and was then diagnosed with neurosyphilis that improved with penicillin. Byrne in 1990 describes a syphilitic paraparesis in a 34-year-old woman who presented with ataxia and secondary syphilis that improved with penicillin and in 2011, Wasserman described a case of a 40-year-old man who presented difficulty walking, facial asymmetry, and numbness in lower legs with a positive VDRL that was also treated successfully with penicillin. In these cases, electrodiagnostics were not consistent with GBS or were not performed [12‐14]. More recently McNiel and Berger describes cases of suspected GBS from syphilis, though each are confounded by other infections including a preceding upper respiratory infection, COVID, or COVID vaccination [15, 16]. In each of the above cases, it remains unclear whether the patient’s polyradiculopathy was demyelinating in nature, or even whether syphilis was the primary inciting factor.

In summary, we believe this case of clinical and electrodiagnostic GBS in the setting of neurosyphilis without other preceding confounders strongly suggests syphilis as the underlying etiology. While penicillin is the mainstay of treatment, it remains unclear whether immunotherapy (immunoglobulins or plasmapheresis) is necessary. This case reiterates the need to include syphilis in the differential of any patient presenting with an acute ascending paralysis concerning for GBS, especially if there is an atypical presentation such as papilledema. This is the case regardless if initial CSF profile is relatively benign, and highlights the need to understand the variety of syphilis presentations as the incidence increases.