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.

Tabes dorsalis in the 19th century. The golden age of progressive locomotor ataxia.

Tabes dorsalis, a late neurological complication of syphilis, is nowadays almost extinct. The path to understanding this disease and its pathophysiology was long and winding, spanning multiple centuries. The 19th century was a crucial period for understanding it. In the first third of the century, German and French physicians defined the semiology of tabes dorsalis, renamed in France "ataxie locomotrice progressive [progressive locomotor ataxia]." Nevertheless, the multiplicity of ancient and recent terms and the description of sometimes unclear nosological concepts (tabes nervosa, tabes spasmodic, nervo-tabes, etc.) were a hindrance to understanding it. Tabes dorsalis was a fertile ground for the description of many clinical signs that have become classics in medicine. No real treatment was available and various unusual therapies were performed. For a long time, the etiology of this disease remained unknown. The link between syphilis and tabes dorsalis was slowly established in the second part of the 19th century from epidemiologic observations. We present an overview of the concept of tabes dorsalis in the medical context of the 19th century and discuss the medical observations of some famous patients suffering from the disease such as Édouard Manet (1832-1883) and Alphonse Daudet (1840-1897).

Classical syphilitic lesions from the museum.

Syphilis is an increasingly diagnosed venereal disease which has four distinctive stages that may last over decades if appropriate treatment is not given. Review of the files of the Pathology Museum in the Faculty of Medicine at The University of Adelaide revealed three cases with classical cardiovascular and neurological findings. Case 1: An 80-year-old man with a large syphilitic aneurysm of the ascending aorta with a smaller aneurysm of the proximal descending aorta. Case 2: A 56-year-old man with chronic syphilitic meningoencephalitis with cerebral atrophy. Case 3: A 77-year-old man with tabes dorsalis. Given the increase in cases coming to medical attention in recent years due to high-risk sexual activity, migration, travel and reduced access to medical treatment, an awareness of the classical features of syphilis is appropriate as some cases will undoubtedly require medicolegal evaluation.

DEVELOPMENT OF GANGLIONOPATHY AND TABETIC VISCERAL CRISES ON THE BACKGROUND OF POLYRADICULONEUROPATHY ASSOCIATED WITH MONOCLONAL GAMMOPATHY (CASE REPORT).

The article presents an analysis of the clinical occurrence of development of chronic polyradiculoneuropathy associated with monoclonal IgG/k (kappa) gammopathy of the undetermined significance. The peculiarity of this occurrence is the uniqueness of the development of the symptoms which are characteristic of tabes dorsalis in this pathology with episodic severe visceral crises and also with ganglionopathy. The example describes the clinical polymorphism of the course of visceral crises, the problems of their diagnosis and as a consequence of inadequate treatment with the development of severe social maladaptation. The importance of timely diagnosis and treatment of such conditions is discussed.

Jules Tinel (1879-1952): Beyond the eponym, the man and his forgotten neurological contributions.

The trauma of World War I had a lasting impact on clinician and physiologist Jules Tinel (1879-1952). His treatment of peripheral nervous system injuries led him, in 1917, to describe the eponymous sign that he linked to activity of the sympathetic nervous system. Among the sequelae of nerve injuries, he was confronted with causalgia that he attributed, here again, to the autonomic nervous system, the main focus of his laboratory research throughout his career. Tinel's sign became so well known that it eclipsed the originality of his seminal descriptions of exertional headache and of hypertensive emergency caused by pheochromocytoma, which could also have been associated with his name. He was always able to marry his clinical practice of neurology and psychiatric consultations with his anatomicopathological, physiological and pathophysiological research, which was based on his daily practice as a physician. At the same time, he directed the work of numerous assistants in his research laboratory, which has since been unjustly forgotten. Several hundreds of scientific publications, including three seminal works, bear witness to his intense activity, which he combined with a genuine talent for teaching and making his findings accessible to a wider public. Those publications alone would fully justify the historical value of extending his renown beyond the existing eponym.

Diphenyl Diselenide Protects Against Mortality, Locomotor Deficits and Oxidative Stress in Drosophila melanogaster Model of Manganese-Induced Neurotoxicity.

Several experimental and epidemiological reports have associated manganese exposure with induction of oxidative stress and locomotor dysfunctions. Diphenyl diselenide (DPDS) is widely reported to exhibit antioxidant, anti-inflammatory and neuroprotective effects in in vitro and in vivo studies via multiple biochemical mechanisms. The present study investigated the protective effect of DPDS on manganese-induced toxicity in Drosophila melanogaster. The flies were exposed, in a dietary regimen, to manganese alone (30 mmol per kg) or in combination with DPDS (10 and 20 µmol per kg) for 7 consecutive days. Exposure to manganese significantly (p < 0.05) increased flies mortality, whereas the survivors exhibited significant locomotor deficits with increased acetylcholinesterase (AChE) activity. However, dietary supplementation with DPDS caused a significant decrease in mortality, improvement in locomotor activity and restoration of AChE activity in manganese-exposed flies. Additionally, the significant decreases in the total thiol level, activities of catalase and glutathione-S-transferase were accompanied with significant increases in the generation of reactive oxygen and nitrogen species and thiobarbituric acid reactive substances in flies exposed to manganese alone. Dietary supplementation with DPDS significantly augmented the antioxidant status and prevented manganese-induced oxidative stress in the treated flies. Collectively, the present data highlight that DPDS may be a promising chemopreventive drug candidate against neurotoxicity resulting from acute manganese exposure.

Édouard Manet's Tabes Dorsalis: From Painful Ataxia to Phantom Limb.

Édouard Manet (1832-1883) is considered the 'father' of Impressionism and even of XXth century modern art. Manet's genius involved getting away from the classical narrative or historical topics and replacing them by the banality of daily life. Technically, he erased volumes into flat two-dimensional coloured planes, and distorted conventional perspective with often gross brushstrokes intentionally giving an 'unfinished' aspect to the work. It is little known that Manet had a very painful second part of his life, due to excruciating limb and chest pains, which developed in parallel with proprioceptive ataxia and gait imbalance. Manet always remained discreet about his private life, and we mainly know that his future wife was his family piano teacher, with whom he had a liaison already at age 17. Later, the great but platonic passion of his life was the painter Berthe Morisot (1841-1895), who got married to Manet's brother Eugène. In fact, we do not know whether he had any mistress at all, although he had several elegant 'flirts' in the mundane and artistic milieu. Thus, while Manet's progressive painful ataxia from age 40 yields little doubt on its tabetic origin, how he contracted syphilis at least 15-20 years before will probably remain a mystery. It is fascinating that Manet's daily struggle against pain and poor coordination may have led his art to become one of the most significant of modern times, opening the way to XXth century avant-gardes, along with another victim of syphilis, Paul Gauguin (1848-1903). Manet never showed any sign of General Paresis, and like his contemporary the writer Alphonse Daudet, his clinical picture remained dominated by paroxysmal pain and walking impairment. Difficult hand coordination made him quit watercolor painting, and during the last 2 years of his life, he had to focus on small format oil works, whose subject was nearly limited to modest bunches of fresh flowers, now often considered to be his maturity masterpieces. Having become bedridden, he had to be amputated of one leg, which was developing gangrene probably associated with ergot overuse. While he died shortly thereafter, we have some witness anecdotes suggesting that he experienced a phantom limb: when Claude Monet (1840-1926) visited him and sat down on his bed, Manet violently shouted at him that he was just sitting on his (absent) leg, which provoked terrible pains. With its facts and mysteries, the subtle interaction between Manet's illness and his work output remains one of the most intriguing stories in neurology of art.

A clinical study of new cases of parenchymal neurosyphilis: has tabes dorsalis disappeared or been missed?

Tabes dorsalis (TD) was documented as the most common parenchymal neurosyphilis, but its incidence dramatically declined in the antibiotic era. Syphilis has resurged on the China mainland since the 1980s. In recent years, physicians have been reporting parenchymal neurosyphilis, and the overwhelming majority was general paresis, but this was not the case in the authors' hospital. To make clear the real situation of parenchymal neurosyphilis in the authors' hospital, a retrospective review was carried out of the records of patients during 2009-2012. Overrepresented clinical new cases of tabetic and paretic parenchymal neurosyphilis were collected. Clinical characteristics, neuroimaging, laboratory data, and responses to penicillin were analyzed in two groups. The efficiency of two current criteria based on CSF antibodies tests was inspected. In the 43 cases with positive serum rapid plasma reagin (RPR) and TPPA tests, 18 patients met the criteria of this study: 11 presented with symptoms of general paresis, and seven had typical presentations of TD. There were statistical differences in serum RPR titers, CSF RPR, white blood cell count, and TP between the paretic and tabetic groups. The response to penicillin was relatively poor in TD. The efficiency of two current criteria was lower in the diagnosis of TD. TD was not uncommon in our area. Its clinical features remained typical, but underdiagnosis with CSF-based criteria and a decreased response to penicillin were prominent issues.

Historical review: suspension therapy for the treatment of tabes dorsalis.

BACKGROUND: Suspension therapy was developed by a Russian doctor, A. Motschutkovsky and at the end of the 19th century it was a popular treatment for tabes dorsalis. It was endorsed by Jean-Martin Charcot in France and Weir Mitchell in the United States; but after 10 years, it was abandoned because it proved to be useless and some patients developed paralysis. SUMMARY: The effect of suspension upon a spinal cord affected by tabes dorsalis and a healthy spinal cord has been analyzed in the light of current knowledge. The benefits of suspension were thought to be due to an improvement in the blood supply to the spinal cord and due to the suggestibility or the placebo effect. Key Message: Analysis of the contemporary literature in the light of current research shows that suspension therapy was a powerful weapon that could cause impairment to the conductivity of the spinal cord and this has important implications for current therapy such as the use of Harrington rods.

A patient with multifocal tabetic arthropathy: a case report and review of literature.

A 55-year-old man presented with a painless destruction of multiple joints and neurologic deficits. He was admitted with a painless pyogenic arthritis of the right ankle. Four years earlier, he had experienced instability of the right knee after an inexplicable, progressive but painless destruction of the joint. Radiographs showed erosive changes at the smaller joints of both hands and the left foot, as well as deformation and destruction of the right foot. Results from both treponemal and nontreponemal serologic test were positive in blood. The Treponema pallidum particle agglutination index was positive in the cerebrospinal fluid. Tabetic arthropathy was diagnosed.Tabetic arthropathy is a manifestation of neurosyphilis. Because syphilis is known as "the great imitator" and tertiary syphilis is rare, recognizing the disease is the biggest challenge for health care providers. Symptoms may mimic any other disease, and many different medical specialists may be faced with these patients, or as Sir William Osler put it: "He who knows syphilis, knows medicine." Initial diagnosis is usually made on serum and cerebrospinal fluid examination. Penicillin is an effective treatment for neurosyphilis to stop progression of neurologic damage, but it does not cure the previously developed tabetic arthropathy. This case is reported to raise awareness of this uncommon but important manifestation of tertiary syphilis. Unfamiliarity with the clinical presentation of tabetic arthropathy may lead to considerable delay in diagnosis.

Clinical spectrum of neurosyphilis among HIV-negative patients in the modern era.

BACKGROUND: The clinical spectrum of neurosyphilis (NS) has changed over time. OBJECTIVE: To describe the clinical spectrum and characteristics of NS in HIV-negative patients. METHODS: A retrospective chart review was performed for 149 in patients with NS. RESULT: All patients were >25 years old, including 16.8% asymptomatic for NS, 15.4% with syphilitic meningitis, 24.2% with meningovascular NS, 38.9% with general paresis, 4.0% with tabes dorsalis and 0.7% with gummatous NS. The original misdiagnosis rate was 84.6%. All 149 patients had positive serum Treponema pallidum particle agglutination (TPPA) and rapid plasma reagin (RPR). The overall positive rates of cerebrospinal fluid RPR (CSF-RPR) and CSF-TPPA were 57.0 and 89.9%, respectively. CSF pleocytosis and elevated CSF protein were found in 40.3% of patients. Nonspecific abnormal brain magnetic resonance imaging and electroencephalography findings were present in 60.4 and 54.8% of NS patients, respectively. CONCLUSIONS: NS has various clinical manifestations, laboratory findings and magnetic resonance imaging and electroencephalography findings, but all studies lack specificity. Every patient with neurological or psychiatric symptoms that are without unambiguous causes should have blood tests for syphilis. When serology proves positive, patients should undergo CSF examination.

John Goodsir (1814-1867) and his neurological illness.

John Goodsir, conservator and professor of anatomy at the University of Edinburgh, suffered an unidentified illness described by experts after his death as tabes. The features that led to this diagnosis, the understanding of tabes at that time and its relationship in some cases to syphilis, are discussed. It is concluded that the most likely diagnoses are subacute combined degeneration of the cord as a result of malnutrition or tabes dorsalis resulting from earlier syphilis. The presence of 'lightning pains' leans towards the latter diagnosis but evidence for a means of acquisition of syphilis is lacking. The disadvantages of retrospective diagnosis are discussed.

Chronic flaccid quadriparesis from tract specific myelopathy in neurosyphilis.

INTRODUCTION: Tract-specific myelopathies with distinctive imaging features are uncommon and typically occur with metabolic or paraneoplastic syndromes. We report a unique case of tract-specific myelopathy with neurosyphilis. CASE PRESENTATION: A 53-year-old male presented with a four-month history of flaccid quadriparesis, sensory loss, and bladder dysfunction. His MRIs revealed striking symmetric T2-weighted hyperintensities in the lateral corticospinal tracts and dorsal columns of the cervical spinal cord that extended rostrally into the pyramidal decussation and medial lemnisci of the medulla oblongata. Nerve conduction and needle electromyography studies excluded axonal or demyelinating lower motor neuron disorders. The patient reported previous untreated primary syphilis and was seropositive on the T.pallidum hemagglutination assay. Penicillin therapy resulted in substantial clinical improvement. DISCUSSION: Although syphilitic meningomyelitis is well-reported, our patient was unique because of the persistent flaccidity (possibly suggesting prolonged spinal shock) and striking tract-specific MRI patterns. These features are novel in syphilitic myelitis and suggest unknown mechanisms of tract-specific tropism and neuronal injury. CONCLUSIONS: "Tract-specific" complete transverse myelopathy with persistent flaccid weakness and areflexia is a novel presentation of neurosyphilis. Early recognition and crystalline penicillin therapy can alleviate morbidity. Our report describes this patient's findings and discusses the differential diagnoses of tract-specific myelopathies.

Syringomyelia associated with syphilitic spinal meningitis: real complication or possible association?

STUDY DESIGN: The study has been designed as a case report. OBJECTIVE: The objective of this study was to report a rare case of syringomyelia in a patient with syphilitic spinal meningitis. SETTING: The Neurology Department, University Hospital Mohamed VI Marrakesh, Morocco. CASE REPORT: A 40-year-old Moroccan male presented with the complaints of weakness of the lower extremities. Neurological examinations confirmed the motor dysfunction of the lower extremities and revealed a sensory loss to the T2-T4 dermatome. The magnetic resonance imaging (MRI) scan detected a hypointense signals on the T1 sequences and hyperintense signals on T2 in the cord extending from C7 to T4. The condition was diagnosed as dorsal syringmyelia. Blood and cerebrospinal fluid were positive for Venereal Disease Research Laboratory and Treponema pallidum hemagglutination tests. The patient was treated with intravenous penicillin therapy with a significant improvement in motor deficit. After 2 years, his neurological deficit was limited to a mild weakness of the distal right leg. CONCLUSION: A case of syphilitic spinal meningitis presenting with syringomyelia, and effectively treated with penicillin has been described.

Magnetic resonance imaging of the spinal cord in a man with tabes dorsalis.

BACKGROUND: Tabes dorsalis is a late manifestation of untreated syphilis that is characterized by ataxia, lancinating pains, and urinary incontinence. A form of tertiary syphilis or neurosyphilis, it is the result of slow, progressive degeneration of the nerve cells in the spinal cord. METHOD: Case report. FINDINGS: A 39-year-old man presented with tingling paresthesia in the lower limbs, difficulty in walking, and loss of vision. Magnetic resonance imaging (MRI) of the dorsal spine showed intramedullary hyperintensity and cord atrophy, similar to changes seen in subacute combined degeneration. MRI features of tabes dorsalis have not been described previously to the best of our knowledge. CONCLUSION: MRI findings in this patient with tabes dorsalis were similar to those seen in subacute combined degeneration, which is characterized predominantly by cord atrophy and intramedullary hyperintensities.

[MRI features of neurosyphilis]. / Aspect IRM de la neuropsyphillis.

INTRODUCTION: Neurosyphilis is rare today. It arises on average 20 years after poorly treated or untreated primary syphilis. Considering the decline in the incidence of syphilitic meningo encephalitis and the little known MRI aspects, we report the case of a patient affected by neurosyphilis occurring after primary syphilis untreated for 25 years. CASE REPORT: A 65-year-old man presented typical clinical features including general paresis with psychiatric disorders, maniac access, and frontal syndrome as well as tabes dorsalis and Argyll-Robertson pupil. Brain MRI showed bilateral high intensity signals on the T2 weighted sequence located in mesiotemporal, insular, frontal regions. CONCLUSIONS: Very few cases of neurosyphilis with detailed brain MRI aspects have been reported. The interest of this case report is first to recall the importance of syphilitic serology in patients with subacute psychiatric disorders and secondly to present rarely reported aspects of the brain MRI.

Syphilitic meningomyelitis misdiagnosed as spinal cord tumor: Case and review.

Context: Syphilitic meningomyelitis is a rare manifestation of neurosyphilis, not well described in the literature.Methods: We reported a rare case of a 29-year-old female with syphilitic meningomyelitis. Her clinical manifestations and imaging findings were discussed with the related literatures reviewed.Results: The patient presented with progressive bilateral lower extremities numbness and weakness for months. Laboratory tests revealed positive serum Treponema pallidum Hemagglutinin Test (TPHA) and rapid plasma reagin test (RPR). The cerebral spinal fluid (CSF) was positive with TPHA but negative for RPR with lymphocytic pleocytosis and elevated protein. Spinal MRI showed swelling and high-signal intensity of thoracic spinal cord except T6-7 level with associated gadolinium enhancement ("flip-flop sign") and peripheral strip-like enhancement on T1WI ("candle guttering appearance"). She was initially diagnosed as spinal cord tumor due to the chronic clinical onset and cord swelling with central enhancement found on thoracic MRI. After dramatic clinical and radiographic improvement with dexamethosone and serological tests of syphilis, she was diagnosed as probable syphilitic meningomyelitis. Till now, there are 12 cases of syphilitic myelitis reported with spinal cord MR images. Thoracic cord is the predominant involved segment (10/12), "candle guttering appearance" is the most common enhancing characteristics of the lesion (7/12), "flip-flop sign" may be seen in the stage with significant inflammation (3/12).Conclusion: Syphilitic meningomyelitis can occur at early or late stage of syphilis, the onset may be acute, subacute or chronic. The imaging findings suggested focal inflammation of the spinal cord. Prognosis is relatively good after proper treatment.

Case report: Neuropathic arthropathy of the hip as a sequela of undiagnosed tertiary syphilis.

BACKGROUND: Neuropathic arthropathy is characterized by rapidly progressive bone destruction in the setting of impaired nociceptive and proprioceptive innervation to the involved joint. It is seen most commonly in the foot and ankle, secondary to peripheral neuropathy in patients with diabetes mellitus. Other less common sites of involvement may include the knee, hip, shoulder, and spine, depending on the underlying etiology. Neuropathic arthropathy can be associated with tabes dorsalis, a unique manifestation of late, tertiary neurosyphilis that may arise in individuals with untreated syphilis many years after initial infection, and usually involves the knee, or less commonly, the hip. CASE REPORT: We report the case of a 73-year-old man with neuropathic arthropathy of the hip and tabes dorsalis attributable to previously undiagnosed tertiary syphilis. There was considerable delay in the diagnosis and unnecessary diagnostic testing owing to failure to consider syphilis as the cause. LITERATURE REVIEW: With the advent of effective antimicrobial therapy and public health campaigns, the relationship between untreated syphilis and neuropathic arthropathy has been primarily a historic point of interest. However, current epidemiologic research suggests a resurgence of syphilis in the United States, with an increased incidence of patients presenting with manifestations of tertiary syphilis from unidentified and untreated primary infections. Treatment options for neuropathic arthropathy of the hip are limited. Arthrodesis has had poor success and treatment with THA has had high complication rates. CONCLUSIONS: Syphilis is not merely a historic cause of neuropathic arthropathy. Neurosyphilis and tabes dorsalis should be considered in the differential diagnosis for patients presenting with rapid joint destruction consistent with Charcot arthropathy and no other apparent cause.

[Juvenile tabes arthropathy: a report of three cases]. / Arthropathie tabétique juvénile: à propos de trois observations.

The authors report three cases revealed by tabes arthropathy in patients younger than 45 years. The age of patients was respectively 42, 40, 42. The clinical symptoms consisted of a painless knee strain, isolated in one case, associated with radiculocordonal posterior syndrome in two cases. The radiological lesions showed bone destruction. The biological assessment was for a venereal disease. The outcome was disappointing, despite a well conducted treatment. The observation of such cases should suggest a syphilitic origin ahead any advanced painless arthropathy even in young patients.