Cerebrospinal Fluid Biomarkers of Symptomatic Neurosyphilis in People With HIV Compared with Uninfected Individuals.

We evaluated the diagnostic clinical performance characteristics (DCPC) of cerebrospinal fluid (CSF) total protein (TP), white blood cell count (WBC), and lactate (LA) with different cutoff points as adjunct biomarkers of confirmed or presumptive symptomatic neurosyphilis (NS) and the impact of HIV infection. From 5,640 participants who underwent lumbar punctures, 236 participants were included, and classified as either people with HIV (PWH) or people without HIV (PWoH) according to the CDC criteria for confirmed NS (n = 42), presumptive NS (n = 74), systemic syphilis (SS) (n = 38), serological diagnosis of syphilis (n = 18), PWH without SS and NS (n = 10), and negative control (n = 72). In PWoH, for presumptive NS, the combination of CSF TP > 45 mg/dL and/or WBC > 5.0 cells/mm3 is valuable for screening, whereas in PWH, it is not recommended for either screening or case-finding NS, however the DCPC were better in the suppressed group. In PWoH, the value of CSF TP > 45 mg/dL is adequate for both screening and confirmation of presumptive NS, subject to prevalence. For WBC count > 20 cell/mm3, the positive predictive value (PPV) of the test is almost perfect, suggesting a confirmatory test. In PWH, CSF TP is an inadequate marker of NS. The WBC count, with cutoffs of > 10 or > 20 cells/mm3, was moderately applicable for screening.As conclusions: CSF WBC count and TP showed distinct DCPC in confirmed or presumptive NS, better in the former. These biomarkers could be included for presumptive NS diagnosis. DCPC of these biomarkers for the diagnosis of NS is greatly affected by HIV co-infection.

Insights Into Treatment Alternatives for Neurosyphilis: Systematic Literature Review and Meta-Analysis.

ABSTRACT: We conducted a systematic literature review and meta-analysis to assess the efficacy of alternative treatments for neurosyphilis. We searched MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Embase, Cochrane, Scopus, and Web of Science from database inception to September 2023, for studies in neurosyphilis that compared penicillin monotherapy with other treatments. We focused on the impact of these therapies on treatment response, but also assessed data regarding reinfection and adverse drug events. Random-effect models were used to obtain pooled mean differences. Of 3415 screened studies, 6 met the inclusion criteria for the systematic literature review. Three studies provided quantitative data that allowed for inclusion in the meta-analysis. Our analysis revealed that the efficacy of intravenous (IV) ceftriaxone 2 g daily for 10 days (51 patients) did not appear statistically different compared with IV penicillin G 18 to 24 million units daily for 10 days (185 patients) for neurosyphilis (pooled odds ratio, 2.85; 95% confidence interval, 0.41-19.56; I 2 = 49%). No statistical difference between ceftriaxone and penicillin was identified in people living with human immunodeficiency virus (HIV) (pooled odds ratio, 4.51; 95% confidence interval, 0.50-40.49; I 2 = 34%). We concluded that alternative therapy with IV ceftriaxone appears similar to penicillin, potentially expanding treatment options for neurosyphilis. Other treatment options including doxycycline warrant further study.

An observational prospective study based on a large cohort of HIV-negative neurosyphilis patients with particular reference to the Jarisch-Herxheimer reaction.

PURPOSE: The purpose of this study is to outline a complete picture of Jarisch-Herxheimer reaction (JHR) in the central nervous system among HIV-negative neurosyphilis patients. METHODS: A prospective study cohort of 772 cases with almost all stages of neurosyphilis depicted the features of JHR including occurrence rate, risk profiles, clinical manifestations, medical management and prognosis. RESULTS: The total occurrence rate of JHR was 9.3% (95% CI, 7.3-11.4%), including 4.1% (95% CI, 2.7-5.6%) with severe JHR. The reaction started 5 h after treatment initiation, peaked after 8 h, and subsided after 18 h. Patients with severe JHR experienced a longer recovery time (26 h). Patients with general paresis (OR = 6.825), ocular syphilis (OR = 3.974), pleocytosis (OR = 2.426), or a high CSF-VDRL titre (per log2 titre increase, OR = 2.235) were more likely to experience JHR. Patients with general paresis had an 11.759-fold increased risk of severe JHR. Worsening symptoms included cognitive impairment, mania, nonsense speech, and dysphoria, while symptoms of hallucination, urination disorder, seizures, myoclonus, or aphasia appeared as new-onset symptoms. Neurosyphilis treatment did not need to be interrupted in most patients with JHR and could be reinstated in patients with seizures under supportive medication when JHR subsided. CONCLUSION: Severe JHR displayed a 4.1% occurrence rate and clinicians should pay particular attention to patients at a higher risk of JHR. The neurosyphilis treatment regime can be restarted under intensive observation for patients with severe JHR and, if necessary, supportive medication should be initiated and continued until the end of therapy.

Enhancing clinical awareness: retrospective analysis of neurosyphilis cases and diagnostic predictors for early recognition and treatment.

OBJECTIVE: This is a retrospective analysis of clinical data from individuals diagnosed with neurosyphilis, aiming to enhance healthcare professionals' understanding of the disease and expedite early diagnosis and intervention. METHODS: A retrospective analysis was conducted on the clinical records of 50 patients who received a diagnosis of symptomatic neurosyphilis and were admitted to the Neurology Department during the period spanning January 2012 to December 2022. RESULTS: Clinical manifestations encompassed diverse phenotypes, with syphilitic meningitis accounting for 16% of cases, characterized by symptoms such as headache, blepharoptosis, paralysis, blurred vision, and tinnitus. Meningovascular syphilis presented in 36% of cases, exhibiting episodic loss of consciousness, limb numbness, and limb convulsion. Paralytic dementia manifested in 36% of cases, featuring symptoms such as memory loss, sluggish response, and slow movement. Tabes dorsalis was observed in 12% of cases, presenting with weakness, numbness, and staggering. Routine cerebrospinal fluid (CSF) analysis indicated abnormal white blood cell counts in 60% of patients, while biochemical testing revealed abnormal protein content in 52% of patients. Notably, statistically significant differences were observed between patients with interstitial and parenchymatous neurosyphilis (Z = 2.023, P = 0.044) in terms of CSF protein content. Electroencephalogram (EEG) results were abnormal in six patients, and imaging studies unveiled diverse findings in 46 patients. CONCLUSION: The study highlights the importance of neurological and/or ocular symptoms in diagnosing symptomatic neurosyphilis. Individuals with hypomnesia should be closely monitored for potential neurosyphilis. Integrating clinical manifestations, laboratory tests, EEG, and imaging can reduce misdiagnosis. This comprehensive approach shows promise in improving early identification and management of neurosyphilis.

Epstein-Barr virus-positive monoclonal lymphoplasmacytic proliferation associated with neurosyphilis in an immunocompetent patient: A case report.

Syphilis is an infectious disease caused by the spirochete bacterium Treponema pallidum. Neurosyphilis results from the infection of the nervous system with Treponema pallidum, which can occur at any stage of syphilis. Neurosyphilis is often overlooked because of its rarity. Early-stage neurosyphilis with brain mass formation is rare. We present a case of early-stage neurosyphilis with prominent Epstein-Barr virus (EBV)-positive monoclonal lymphoplasmacytic proliferation in an immunocompetent patient. A 36-year-old man presented with a chief complaint of a progressively worsening headache, a newly developed skin rash, and a fever. Magnetic resonance imaging showed a mass lesion, which measured 18 mm in diameter, in the left frontal lobe of the cerebrum. The patient underwent an emergency operation to remove the abscess. A pathological investigation revealed complex findings. There was an abscess in the cerebrum. Lymphoplasmacytic meningitis was also noted. In addition, a vaguely nodular lesion, which was composed of plasmacytoid and lymphoid cells, was observed around the abscess. Immunohistochemically, an anti-Treponema pallidum antibody revealed numerous Treponemas around the abscess. In situ hybridization revealed that the plasmacytoid and lymphoid cells were Epstein-Barr encoding region (EBER)-positive; κ-positive cells were significantly more prevalent than λ-positive cells, suggesting light-chain restriction. Postoperatively, parenteral antibiotics were administered for four weeks. The patient has been free of recurrence for two years since the surgery. No association between neurosyphilis and EBV-positive lymphoplasmacytic proliferation has ever been reported. Mass formation in early-stage neurosyphilis is an exceptionally rare event. The present case indicates that in syphilis patients, lymphoproliferative disorders that lead to mass formation may be caused by concomitant EBV reactivation. Furthermore, when treating patients with mass lesions of the central nervous system, it is important to check their medical history and perform laboratory screening for infectious diseases to avoid overlooking syphilis infections.

A Cluster of Ocular Syphilis Cases with a Common Sex Partner - Southwest Michigan, 2022.

Untreated syphilis can lead to ocular syphilis, otosyphilis, and neurosyphilis, conditions resulting from Treponema pallidum infection of the eye, inner ear, or central nervous system. During March-July 2022, Michigan public health officials identified a cluster of ocular syphilis cases. The public health response included case investigation, partner notification, dissemination of health alerts, patient referral to a public health clinic for diagnosis and treatment, hospital care coordination, and specimen collection for T. pallidum molecular typing. Five cases occurred among southwest Michigan women, all of whom had the same male sex partner. The women were aged 40-60 years, HIV-negative, and identified as non-Hispanic White race; the disease was staged as early syphilis, and all patients were hospitalized and treated with intravenous penicillin. The common male sex partner was determined to have early latent syphilis and never developed ocular syphilis. No additional transmission was identified after the common male partner's treatment. Due to lack of genetic material in limited specimens, syphilis molecular typing was not possible. A common heterosexual partner in an ocular syphilis cluster has not been previously documented and suggests that an unidentified strain of T. pallidum might have been associated with increased risk for systemic manifestations of syphilis. A high index of clinical suspicion and thorough sexual history are critical to diagnosing ocular syphilis, otosyphilis, and neurosyphilis. Coordination of disease surveillance with disease intervention specialist investigation and treatment referral can interrupt syphilis transmission.

Neurosyphilis presenting with Guillain-Barre syndrome: a case report.

BACKGROUND: Syphilis is associated with a wide variety of systemic presentations, earning it the moniker "The great mimicker". Neurosyphilis is classically associated with meningovasculitis in the acute-subacute stage and tabes dorsalis and dementia paralytica in later stages. However, one of the less well described presentations include Guillain-Barre Syndrome. This case presents a patient with an ascending polyneuropathy suspicious for Guillain-Barre Syndrome who also had other atypical findings including a truncal sensory loss, optic disc swelling, and rash ultimately found to have neurosyphilis. Electrodiagnostic testing was consistent with demyelination, supporting a diagnosis of neurosyphilis associated Guillain-Barre Syndrome. CASE PRESENTATION: A 37-year-old female presented to the emergency department with a weakness and difficulty swallowing. She described a three-month history of symptoms, initially starting with a persistent headache followed by one month of a pruritic rash on her chest, palms, and soles. Two weeks prior to presentation, she developed progressive weakness in her arms, numbness in her arms and chest, and difficulty swallowing. Neurological exam was notable for multiple cranial neuropathies, distal predominant weakness in all extremities, length-dependent sensory loss, and hyporeflexia. Investigation revealed a positive Venereal Disease Research Laboratory in her cerebrospinal fluid without significant pleocytosis, contrast enhancement in cranial nerves V, VII, and VIII on MRI, and a demyelinating polyneuropathy on electrodiagnostic testing. She was diagnosed with Guillain-Barre syndrome, secondary to neurosyphilis. The patient acutely declined and required intubation, and ultimately made a full recovery after treatment with plasmapheresis and penicillin. CONCLUSIONS: This case describes a clinical entity of syphilitic Guillain-Barre Syndrome and highlights the importance of including syphilis in the differential of any patient presenting with ascending polyradiculopathy, especially given the resurgence of syphilis.

Neurosyphilis in a young man having HIV infection, blurring of vision and skin rash.

We report a 22-year-old homosexual man, a known case of HIV-1 infection but non-compliant to medications, who presented with a 5-month history of progressive painless non-pruritic coin-shaped skin lesions and recent gradual bilateral blurring of vision. His history divulged a primary syphilitic event 1 year prior to the present clinical manifestations. Investigation led to the diagnosis of neurosyphilis with ocular involvement with concurrent signs of secondary syphilis. Treatment with aqueous crystalline penicillin G, ophthalmic steroid and tropicamide drops, and topical emollients resulted in significant clinical improvement of ocular symptoms and skin lesions. The diagnosis of neurosyphilis requires a high degree of clinical suspicion and should be included in the differential diagnosis of unexplained ocular symptoms, particularly in men who have sex with men and HIV-infected patients. This is necessary for the early diagnosis, appropriate management, and good outcome of these patients.

[Neurosyphilis or not - a case of a differential diagnostic challenge]. / Neurosyphilis vagy nem ­ egy differenciáldiagnosztikai kihívás esete.

We report the case of a 42-year-old woman with paraparesis associated with transverse myelitis. For differential diagnostics detailed microbiological, cerebrospinal fluid (CSF) and neuroimaging examinations were performed. Syphilis was confirmed, but diagnosis of neurosyphilis was only probable based on the CSF microbiological test results. The beneficial treatment response to application of the therapeutic protocol for syphilis supported the supposed diagnosis of syphilis-associated myelitis in our case. In this case report we reviewed the differential diagnostic tools of myelopathies/myelitis.
Nowadays regarding to growing prevalence of syphilis worldwide physicians should face on its presence and medical consequences.

Clinical outcomes of HIV-syphilis coinfection among patients with no neurological symptoms: a retrospective cohort study.

OBJECTIVE: Our objective was to describe and compare the occurrence of neurological outcomes and neurosyphilis in people living with HIV with incident syphilis and no neurological symptoms who underwent early screening for asymptomatic neurosyphilis (ANS) or regular clinical management without a lumbar puncture. METHODS: This was a retrospective cohort study in a single referral centre of Sao Paulo, Brazil. Patients with incident syphilis diagnosed between January 2000 and August 2016 and meeting the adapted criteria for ANS investigation suggested by Marra et al. (CD4+ T-cell counts ≤350 cells/mm³ and/or venereal disease research laboratory test results ≥1:16) were identified. Those with no neurological symptoms and immediately referred for lumbar puncture were categorized as group 1, and those not referred for cerebrospinal fluid collection were categorized as group 2. We compared the occurrence of neurological symptoms and neurosyphilis diagnoses between the groups using incidence rates and Kaplan-Meier curves. RESULTS: We included 425 participants with a median follow-up of 6 years. The incidence rate of neurological symptoms was 36.5/1000 person-years in group 1 and 40.6/1000 person-years in group 2 (incidence rate ratio [IRR] 0.90; 95% confidence interval [CI] 0.57-1.39; p = 0.62). The incidence rate of neurosyphilis was 15.0 cases/1000 person-years in group 1 and 6.7 cases/1000 person-years in group 2 (IRR 2.26; 95% CI 0.93-5.68; p = 0.05). CONCLUSIONS: We found no statistically significant differences between groups in the incidence rates of neurological symptoms and neurosyphilis. Our findings support the current guidelines, which suggest a less invasive approach regarding ANS investigation among people living with HIV with incident syphilis.

Clinical and laboratory features in patients with positive syphilis serology presenting with acute ischemic stroke or transient ischemic attack: a prospective cohort study.

BACKGROUND: Neurosyphilis (NS) can lead to acute ischemic stroke (AIS) or transient ischemic attack (TIA). We compared the clinical characteristics and laboratory features among AIS and TIA patients who were syphilis-seronegative (control group) or had latent syphilis (LS) or NS to evaluate their stroke outcome. METHODS: This prospective cohort study was conducted on patients who had recently suffered AIS or TIA. After serological syphilis screening, clinical and laboratory data were collected, and brain imaging and spinal tap (serologically syphilis-positive patients only) were performed. Stroke outcome was re-evaluated approximately three months later. RESULTS: The 344 enrolled patients were divided into three groups: control group (83.7%), LS (13.1%), and NS (3.2%). A multivariate analysis revealed: 1) age of ≥ 70 years, generalized brain atrophy via imaging, and alopecia (adjusted odds ratio [AOR] = 2.635, 2.415, and 13.264, respectively) were significantly associated with LS vs controls; 2) age of ≥ 70 years (AOR = 14.633) was significantly associated with NS vs controls; and 3) the proportion of patients with dysarthria was significantly lower (AOR = 0.154) in the NS group than in the LS group. Regarding the NS patient cerebrospinal fluid (CSF) profile, only 2/11 cases had positive CSF-Venereal Disease Research Laboratory (VDRL) test results; the other nine cases were diagnosed from elevated white blood cell counts or protein levels combined with positive CSF fluorescent treponemal antibody absorption (FTA-ABS) test results. Regarding disability, the initial modified Rankin scale (mRS) score was lower in the control group than in the NS group (p = 0.022). At 3 months post-stroke, the mRS score had significantly decreased in the control (p < 0.001) and LS (p = 0.001) groups. Regarding activities of daily living, the 3-month Barthel Index (BI) score was significantly higher in control patients than in LS (p = 0.030) or NS (p = 0.002) patients. Additionally, the 3-month BI score was significantly increased in the control (p < 0.001) and LS (p = 0.001) groups. CONCLUSIONS: Because syphilis was detected in many AIS and TIA patients, especially those aged ≥ 70 years, routine serological syphilis screening may be warranted in this population. Patients with syphilitic infection had worse stroke outcomes compared with NS patients.

Neuropsychological Features in Patients with General Paresis of the Insane at an Early Stage.

BACKGROUND This study aimed to explore the features of cognitive impairment in patients with neurosyphilis at the early stage of mild cognitive impairment (MCI). MATERIAL AND METHODS A total of 18 patients with asymptomatic neurosyphilis (ANS), 19 patients with neurosyphilis at the MCI stage (neurosyphilis-MCI), and 15 patients with neurosyphilis at the dementia stage (neurosyphilis-dementia) were enrolled. Cognitive function was evaluated using comprehensive rating scales. Tests of syphilis in blood and cerebrospinal fluid (CSF) were conducted, and white blood cell (WBC) counts and protein levels in CSF were measured. RESULTS Overall cognitive function and individual cognitive domains, including memory, language, visuospatial skill, and attention/executive function, were all significantly impaired in the neurosyphilis-MCI group compared with the ANS group, and were further impaired in the neurosyphilis-dementia group. Although there was no difference in serum rapid plasma regain (RPR) titer among the 3 groups, the number of patients with serum RPR titer ≥1: 32 in the neurosyphilis-MCI group was much higher than that in the ANS group. CSF RPR positive rate in the neurosyphilis-MCI group was significantly higher than that in the ANS group. The WBC count, protein level, and the rate of elevated protein level or increased WBC count in CSF did not differ among the 3 groups. CONCLUSIONS The feature of cognitive impairment of neurosyphilis-MCI patients displayed multiple-domain amnestic MCI. Perhaps there were extensive brain areas involved at the early stage, and a continuous neuroinflammatory process was through the different stages of neurosyphilis. Early diagnosis and treatment are very important for preventing the progression of general paresis of the insane.

Incidental finding of neurosyphilis with intracranial hemorrhage and cerebral infarction: A case report.

Syphilis has recently increased in prevalence in Japan. Neurosyphilis is a special pathological condition of syphilis well known to cause cerebral vasculitis and ischemic stroke. Neurosyphilis in the meningovascular stage rarely causes caliber irregularity of the cerebral blood vessels or cerebral hemorrhage. We describe the case of a 49-year-old Japanese man with neurosyphilis. Cerebral hemorrhage, multiple cerebral infarctions, and caliber irregularity of the cerebral blood vessels were observed, the patient underwent surgery for cerebral hemorrhage on the day of admission, all of which were suspected to be caused by syphilis. He was started on an antibacterial treatment of penicillin on the day of admission and was diagnosed with neurosyphilis the following week based on his serum and spinal fluid test results. His condition improved, and he was transferred to another hospital after 4 weeks of treatment consisting of 3 weeks of infusion treatment with benzylpenicillin followed by oral treatment with amoxicillin. To the best of our knowledge, this is a rare case of neurosyphilis in conjunction with cerebral hemorrhage and cerebral infarction. Clinicians should consider syphilis in the differential diagnosis of cerebral hemorrhage and cerebral infarction and test patients for sexually transmitted diseases, in addition to cerebrospinal fluid testing, when cerebral hemorrhage occurs with an unknown cause. This is especially pertinent when patients present with cerebral infarction or caliber irregularity of the cerebral blood vessels.

Syphilis with diplopia. / Syfilis med dobbeltsyn.

BACKGROUND: Syphilis is a sexually transmittable infectious disease caused by the spirochaete Treponema pallidum, which classically causes symptoms in three stages. CASE PRESENTATION: A previously healthy male in his thirties was admitted to our department after suffering from diplopia and unilateral ptosis for two days. Clinical examination revealed a left-sided oculomotor palsy with an ipsilateral ptosis. Supplementary cerebral computer tomography with angiography and magnetic resonance imaging was normal except for lymphadenopathy in the neck and mediastinum. As the patient was homosexual, we chose to test for HIV. The doctor on duty, being from Belarus where syphilis was recognised as endemic during her studies, also screened for syphilis. The HIV test was negative, while the syphilis test was positive. Lumbar puncture showed moderate pleocytosis and positive serology for syphilis, confirming the diagnosis of neurosyphilis. The patient recovered fully after a course of penicillin. INTERPRETATION: Even though syphilis remains uncommon in Norway, the incidence has been increasing in recent decades, especially in male homosexual communities. Patients may subsequently present with a diversity of symptoms.

Secondary syphilis with ocular involvement in a HIV-infected patient - case report.

We describe the case of a HIV-infected patient, in whom a secondary syphilis with skin lesions and ocular involvement developed. On admission papular skin rash and partial visual loss with left eye were observed. Serological tests for syphilis were positive in very high titers. Ophthalmological examination revealed ocular abnormalities indicating ocular syphilis. Cerebrospinal fluid (CSF) tests showed elevated concentration of immunoglobulin G (IgG) with normal white blood count and albumin concentration, serological treponemal tests for syphilis were positive. Intravenous therapy with Penicillinum Crystallisatum (Benzylpenicillinum kalicum) was administered, according to the neurosyphilis treatment schedule, achieving resolution of the skin lesions and partial vision improvement, a month after the end of the treatment a complete recovery of the vision was noted. Serological tests` for syphilis titers decreased fourfold. Described case confirms reasonability of examination for syphilis in patients with sudden vision disturbances, especially those HIV-infected. It also indicates that early appropriate treatment of the ocular syphilis prevents permanent loss of vision.

Diagnosis of Syphilitic Bilateral Papillitis Mimicking Papilloedema.

Syphilis produces myriad nonspecific signs and symptoms. For example, optic disk swelling might be seen in patients with syphilis as a result of cranial hypertension (papilloedema), inflammatory optic neuritis with papillitis, or optic perineuritis. We report a case involving differential diagnosis of syphilitic bilateral papillitis mimicking papilloedema.

Persistent Verrucous Plaques in an HIV-Positive Patient With Secondary and Neurosyphilis.

A 23-year-old HIV-positive woman presented with persistent yellowish verrucous plaques on both ankles, which had been present for 2 years, and blurred vision, which had persisted for 1 month. Serological tests confirmed a syphilis diagnosis. Her condition improved after systemic penicillin treatment, with no topical treatment except petrolatum ointment.

Neurosyphilis presenting with myelitis-case series and literature review.

Syphilitic myelitis is an extremely rare manifestation of neurosyphilis and often misdiagnosed. However, a small amount of literature describe its clinical manifestations and neuroimaging features, and there is no relevant data on the prognosis, especially the long follow-up prognosis. In this paper, four syphilitic myelitis patients admitted to our hospital between July 2012 and July 2017 were retrospectively reviewed. Of the four patients, two females and two males. Treatment included intravenous penicillin G, with 24 million units of penicillin G per day administered intravenously for 14 days. Three patients were also treated with corticosteroids. The prognosis were well in three cases who received early anti-syphilis treatment, but one case who received delayed treatment due to misdiagnosis had no improvement. Neurosyphilis should be considered when there is long-segment myelopathy. Anti-treponemal antibiotics and corticosteroid therapy may improve neurological prognosis.

The Devil Is in the Details: Neurological Diseases Presenting as Religious Hallucinations in Two Literary Works.

Few authors in the Western literature have acquired such a monumental reputation as Thomas Mann and Fyodor Dostoyevsky; although with different backgrounds and aesthetic peculiarities, their writings converge thematically in their frequent relationship with disease. From Dostoyevsky's struggle with epilepsy to Mann's descriptions of tuberculosis and cholera, many are the examples found in their body of work describing medical afflictions. One noteworthy similarity in their works is the presence of hallucinations with Mephistopheles-like devilish entities, possibly caused by neurological diseases: in Mann's case, concerning the main character of Doctor Faustus, caused by neurosyphilis, while for Dostoyevsky, concerning one of the titular Brothers Karamazov, by delirium tremens. In both cases, the authors leave room for ambiguity, with the characters themselves casting doubts on whether their experiences were indeed caused by their disease or by an actual supernatural being. In this, we may find an interesting intersection between neurology and the literature.