Dental Caries Postradiotherapy in Head and Neck Cancer.

BACKGROUND: Treatment for head and neck cancer (HNC) such as radiotherapy (RT) can lead to numerous acute and chronic head and neck sequelae, including dental caries. The goal of the present study was to measure 2-y changes in dental caries after radiotherapy in patients with HNC and test risk factors for caries increment. METHODS: Cancer and dental disease characteristics, demographics, and oral health practices were documented before and 6, 12, 18, and 24 mo after the start of RT for 572 adult patients with HNC. Patients were eligible if they were age 18 y or older, diagnosed with HNC, and planned to receive RT for treatment of HNC. Caries prevalence was measured as decayed, missing, and filled surfaces (DMFS). The association between change in DMFS and risk factors was evaluated using linear mixed models. RESULTS: On average, DMFS increased from baseline to each follow-up visit: 6 mo, +1.11; 12 mo, +2.47; 18 mo, +3.43; and 24 mo, +4.29 (P < 0.0001). The increase in DMFS during follow-up was significantly smaller for the following patient characteristics: compliant with daily fluoride use (P = 0.0004) and daily oral hygiene (brushing twice daily and flossing daily; P = 0.015), dental insurance (P = 0.004), and greater than high school education (P = 0.001). DMFS change was not significantly associated with average or maximum RT dose to the parotids (P > 0.6) or salivary flow (P > 0.1). In the subset of patients who had salivary hypofunction at baseline (n = 164), lower salivary flow at follow-up visits was associated with increased DMFS. CONCLUSION: Increased caries is a complication soon after RT in HNC. Fluoride, oral hygiene, dental insurance, and education level had the strongest association with caries increment after radiotherapy to the head and neck region. Thus, intensive oral hygiene measures, including fluoride and greater accessibility of dental care, may contribute to reducing the caries burden after RT in HNC. KNOWLEDGE TRANSFER STATEMENT: The results of this study can be used by clinicians when deciding how to minimize oral complications related to cancer therapy for patients with head and neck cancer. Identification of modifiable factors (e.g., oral hygiene and prescription fluoride compliance) associated with increased caries risk can minimize radiation caries burden.

The Histopathology of Oral Cancer Pain in a Mouse Model and a Human Cohort.

Oral cancer patients often have severe, chronic, and mechanically induced pain at the site of the primary cancer. Oral cancer pain is initiated and maintained in the cancer microenvironment and attributed to release of mediators that sensitize primary sensory nerves. This study was designed to investigate the histopathology associated with painful oral cancers in a preclinical model. The relationship of pain scores with pathologic variables was also investigated in a cohort of 72 oral cancer patients. Wild-type mice were exposed to the carcinogen, 4-nitroquinoline 1-oxide (4NQO). Nociceptive (pain) behavior was measured with the dolognawmeter, an operant device and assay for measuring functional and mechanical allodynia. Lesions developed on the tongues and esophagi of the 4NQO-treated animals and included hyperkeratoses, papillomas, dysplasias, and cancers. Papillomas included lesions with benign and dysplastic pathological features. Two histologic subtypes of squamous cell carcinomas (SCCs) were identified-SCCs with exophytic and invasive components associated with papillary lesions (pSCCs) and invasive SCCs without exophytic histology (iSCCs). Only the pSCC subtype of tongue cancer was associated with nociceptive behavior. Increased tumor size was associated with greater nociceptive behavior in the mouse model and more pain experienced by oral cancer patients. In addition, depth of invasion was associated with patient-reported pain. The pSCC histology identifies 4NQO-induced tongue cancers that are expected to be enriched for expression and release of nociceptive mediators.

No longer a historical ailment: two cases of childhood scurvy with recommendations for bone health providers.

PURPOSE: Scurvy, due to vitamin C deficiency, is commonly referenced as a "forgotten" or "historical" disease. A growing number of case reports challenge this notion. Bone health providers are often consulted early in the presentation of scurvy to evaluate musculoskeletal complaints resulting from impaired collagen production and disrupted endochondral bone formation. In this report, we describe two cases of childhood scurvy. Our objective is to summarize the key features of scurvy for bone health providers, with the goal of raising awareness and facilitating diagnosis in future cases. CASE DESCRIPTIONS: Case one occurred in a 12-year-old non-verbal, non-ambulatory female on a ketogenic diet for refractory epilepsy. Clinical findings included hemarthrosis, transfusion dependent anemia, elevated inflammatory markers, and epiphysiolysis. Magnetic resonance imaging (MRI) revealed multi-focal bone marrow signal abnormalities and physeal irregularities. Case two occurred in a typically developing 5-year-old male presenting with limp and knee pain. Symptoms progressed despite casting and immobilization. Mild anemia, elevated inflammatory markers, and multi-focal marrow and physeal MRI abnormalities were identified. Subsequent dietary history revealed total absence of fruit or vegetable consumption. The diagnosis of scurvy was confirmed in both cases by undetectable plasma vitamin C concentrations. Treatment with vitamin C led to rapid clinical improvement. CONCLUSION: Scurvy can no longer be considered a historical diagnosis and should not be forgotten when evaluating children with musculoskeletal ailments. Early recognition of the signs, symptoms, and imaging findings of scurvy can reduce the clinical burden of this disease with the timely initiation of vitamin C therapy.

Targeted TNF-α Overexpression Drives Salivary Gland Inflammation.

Chronic inflammation of the salivary glands from pathologic conditions such as Sjögren's syndrome can result in glandular destruction and hyposalivation. To understand which molecular factors may play a role in clinical cases of salivary gland hypofunction, we developed an aquaporin 5 (AQP5) Cre mouse line to produce genetic recombination predominantly within the acinar cells of the glands. We then bred these mice with the TNF-αglo transgenic line to develop a mouse model with salivary gland-specific overexpression of TNF-α; which replicates conditions seen in sialadenitis, an inflammation of the salivary glands resulting from infection or autoimmune disorders such as Sjögren's syndrome. The resulting AQP5-Cre/TNF-αglo mice display severe inflammation in the salivary glands with acinar cell atrophy, fibrosis, and dilation of the ducts. AQP5 expression was reduced in the salivary glands, while tight junction integrity appeared to be disrupted. The immune dysregulation in the salivary gland of these mice led to hyposalivation and masticatory dysfunction.

RAF Kinase Inhibitory Protein Expression and Phosphorylation Profiles in Oral Cancers.

Raf Kinase Inhibitory Protein (RKIP) expression has been profiled for a number of unique tissue cancers. However, certain tissues have not been explored, and oral and oropharyngeal cancers stand out as high priority targets, given their relatively high incidence, high morbidity rate, and in many cases, preventable nature. The purpose of this study was to examine changes in RKIP expression and phosphorylation in tissues resected from oral cancer patients, and compare to results generated from immortalized cell lines raised from primary oral cancer tissues, including oral squamous cell carcinoma line 4 (SCC4) and human squamous cell carcinoma line 3 (HSC3). Out of 4 human samples collected from male and female patients across various ages with variable risk factors, we observed an across the board reduction in RKIP expression. Two human samples demonstrated a significant increase in phosphorylated RKIP when normalized to total RKIP, however all 4 were increased when normalized to total cellular protein. The immortalized oral cancer cell culture HSC3 revealed significant increases in phosphorylated RKIP with no change in total RKIP expression, while line SCC4 demonstrated an increase in both total and phosphorylated RKIP. Results presented here indicate that oral cancers behave similarly to other cancers in terms of changes in RKIP expression and phosphorylation, although immortalized cell line expression profiles significantly differ from human tissue biopsies.

Conditional TNF-α Overexpression in the Tooth and Alveolar Bone Results in Painful Pulpitis and Osteitis.

Tumor necrosis factor-α (TNF-α) is a proalgesic cytokine that is commonly expressed following tissue injury. TNF-α expression not only promotes inflammation but can also lead to pain hypersensitivity in nociceptors. With the established link between TNF-α and inflammatory pain, we identified its increased expression in the teeth of patients affected with caries and pulpitis. We generated a transgenic mouse model (TNF-α(glo)) that could be used to conditionally overexpress TNF-α. These mice were bred with a dentin matrix protein 1 (DMP1)-Cre line for overexpression of TNF-α in both the tooth pulp and bone to study oral pain that would result from subsequent development of pulpitis and bone loss. The resulting DMP1/TNF-α(glo) mice show inflammation in the tooth pulp that resembles pulpitis while also displaying periodontal bone loss. Inflammatory infiltrates and enlarged blood vessels were observed in the tooth pulp. Pulpitis and osteitis affected the nociceptive neurons innervating the orofacial region by causing increased expression of inflammatory cytokines within the trigeminal ganglia. With this new mouse model morphologically mimicking pulpitis and osteitis, we tested it for signs of oral pain with an oral function assay (dolognawmeter). This assay/device records the time required by a mouse to complete a discrete gnawing task. The duration of gnawing required by the DMP1/TNF-α(glo) mice to complete the task was greater than that for the controls; extended gnaw time in a dolognawmeter indicates reduced orofacial function. With the DMP1/TNF-α(glo) mice, we have shown that TNF-α expression alone can produce inflammation similar to pulpitis and osteitis and that this mouse model can be used to study dental inflammatory pain.

Review of preclinical studies on treatment of mucositis and associated pain.

Oral mucositis is a significant problem in cancer patients treated with radiation or chemotherapy, often hindering definitive cancer treatment. For patients with oral mucositis, pain is the most distressing symptom, leading to loss of orofacial function and poor quality of life. While oral mucositis has been well-described, its pathophysiology is poorly understood. Oral health professionals treating patients with mucositis have almost no effective therapies to treat or prevent oral mucositis. The purpose of this review is to (1) describe the current preclinical models of oral mucositis and their contribution to the understanding of mucositis pathophysiology, (2) explore preclinical studies on therapies targeting mucositis and discuss the clinical trials that have resulted from these preclinical studies, and (3) describe the proposed pathophysiology of oral mucositis pain and preclinical modeling of oral mucositis pain.

Metastatic epithelioid angiosarcoma to the mandible: report of a case and review of the literature.

Angiosarcoma and its epithelioid variant are vascular malignancies that rarely affect the facial skeleton. Epithelioid angiosarcoma resembles carcinoma and can be difficult to diagnose. A case is presented of metastatic epithelioid angiosarcoma to the mandible from an angiosarcomatoid portion of renal carcinoma. The diagnostic challenge is outlined and the literature is reviewed.

Biologic mechanisms of oral cancer pain and implications for clinical therapy.

Cancer pain is an ever-present public health concern. With innovations in treatment, cancer patients are surviving longer, but uncontrollable pain creates a poor quality of life for these patients. Oral cancer is unique in that it causes intense pain at the primary site and significantly impairs speech, swallowing, and masticatory functions. We propose that oral cancer pain has underlying biologic mechanisms that are generated within the cancer microenvironment. A comprehensive understanding of key mediators that control cross-talk between the cancer and peripheral nervous system, and possible interventions, underlies effective cancer pain management. The purpose of this review is to explore the current studies on oral cancer pain and their implications in clinical management for cancer pain in general. Furthermore, we will explore the endogenous opioid systems and novel cancer pain therapeutics that target these systems, which could solve the issue of opiate tolerance and improve quality of life in oral cancer patients.

Gauze padding: a simple technique to delineate small oral cavity tumors.

BACKGROUND AND PURPOSE: Small oral cavity tumors are an imaging challenge. Intimate apposition of vestibular oral mucosa to the alveolar mucosa makes tumor assessment difficult. In CT imaging, the "puffed cheek" method has been used to separate surfaces, though this is not feasible with long MR imaging sequences. We implemented placement of 2 × 2 inch (6.45 cm) gauze into the oral vestibule before the MR imaging examination, to determine whether this might improve tumor visualization. MATERIALS AND METHODS: MR imaging examinations of all T1 oral malignant tumors treated at University of California, San Francisco, by the Oral and Maxillofacial Department were reviewed by 2 neuroradiologists. Nine patients were included in the final analysis. Six patients were imaged by using a standard protocol. Three patients were imaged with gauze placement. The radiologists evaluated the MR images, assessing whether they could see the tumor and then fully delineate it and its thickness. RESULTS: Fisher exact analysis was performed on questions 1, 2, and 4 with the following results: P value = .048, Can you see the tumor? P value = .012, Can you fully delineate? P value of .012, How confident are you? MR imaging examinations with gauze clearly delineated the tumor with the tumor thickness measurable. MR imaging examinations without gauze did not clearly show the tumor or its thickness. Confidence of interpretation of the findings was also increased when gauze was used. CONCLUSIONS: A 2 × 2 inch (6.45 cm) rolled gauze in the oral vestibule significantly improved tumor localization and delineation at MR imaging. This technique is simple and provides superior preoperative imaging evaluation and treatment planning of small oral cavity tumors.

Serine proteases and protease-activated receptor 2-dependent allodynia: a novel cancer pain pathway.

Mediators involved in the generation of pain in patients with cancer are poorly understood. Using a combined molecular, pharmacologic, behavioral, and genetic approach, we have identified a novel mechanism of cancer-dependent allodynia induced by protease-activated receptor 2 (PAR2). Here we show that human head and neck carcinoma cells have increased levels of proteolytic activity compared to normal human cell controls. Supernatant from human carcinoma cells, but not controls, caused marked and prolonged mechanical allodynia in mice, when administered into the hindpaw. This nociceptive effect was abolished by serine protease inhibition, diminished by mast cell depletion and absent in PAR2-deficient mice. In addition, non-contact co-culture of trigeminal ganglion neurons with human head and neck carcinoma cells increased the proportion of neurons that exhibited PAR2-immunoreactivity. Our results point to a direct role for serine proteases and their receptor in the pathogenesis of cancer pain. This previously unrecognized cancer pain pathway has important therapeutic implications wherein serine protease inhibitors and PAR2 antagonists may be useful for the treatment of cancer pain.

Stromal control of oncogenic traits expressed in response to the overexpression of GLI2, a pleiotropic oncogene.

Hedgehog signaling is often activated in tumors, yet it remains unclear how GLI2, a transcription factor activated by this pathway, acts as an oncogene. We show that GLI2 is a pleiotropic oncogene. The overexpression induces genomic instability and blocks differentiation, likely mediated in part by enhanced expression of the stem cell gene SOX2. GLI2 also induces transforming growth factor (TGF)B1-dependent transdifferentiation of foreskin and tongue, but not gingival fibroblasts into myofibroblasts, creating an environment permissive for invasion by keratinocytes, which are in various stages of differentiation having downregulated GLI2. Thus, upregulated GLI2 expression is sufficient to induce a number of the acquired characteristics of tumor cells; however, the stroma, in a tissue-specific manner, determines whether certain GLI2 oncogenic traits are expressed.

Lingual nerve damage due to inferior alveolar nerve blocks: a possible explanation.

BACKGROUND: An explanation for the predominance of injuries to lingual nerves over those to inferior alveolar nerves as a result of inferior alveolar nerve blocks may be due to the nerves' fascicular pattern. A unifascicular nerve may be injured more easily than a multifascicular nerve. METHODS: The authors unilaterally dissected lingual and inferior alveolar nerves from 12 cadavers. They cut the specimens 2 millimeters above the lingula for both the lingual nerve and inferior alveolar nerve and opposite the site of the middle of the third molar for the lingual nerve, and they counted the number of fascicles at each site. RESULTS: For the lingual nerve at the lingula, the mean number of fascicles was three (range, one to eight). Four of the 12 nerves (33 percent) were unifascicular at this point. Opposite the third molar, the lingual nerve had a mean of 20 fascicles (range, six to 39). In every case, there were more fascicles in the third molar region than above the lingula in the same nerve. At the lingula, the inferior alveolar nerve had a mean of 7.2 fascicles (range, three to 14). CONCLUSION: This study may explain the observation that when an inferior alveolar nerve block causes permanent nerve impairment, the lingual nerve is affected about 70 percent of the time and the inferior alveolar nerve is affected only 30 percent of the time. In 33 percent of cases, the lingual nerve had only one fascicle at the lingula; a unifascicular nerve may be injured more easily than a multifascicular one. CLINICAL IMPLICATIONS: There is no known way to avoid the remote possibility of nerve damage resulting from an inferior alveolar nerve block. The lingual nerve may be predominantly affected because of its fascicular pattern.

Importance of sample preparation for molecular diagnosis of lyme borreliosis from urine.

Urine PCR has been used for the diagnosis of Borrelia burgdorferi infection in recent years but has been abandoned because of its low sensitivity and the irreproducibility of the results. Our study aimed to analyze technical details related to sample preparation and detection methods. Crucial for a successful urine PCR were (i) avoidance of the first morning urine sample; (ii) centrifugation at 36,000 x g; and (iii) the extraction method, with only DNAzol of the seven different extraction methods used yielding positive results with patient urine specimens. Furthermore, storage of frozen urine samples at -80 degrees C reduced the sensitivity of a positive urine PCR result obtained with samples from 72 untreated erythema migrans (EM) patients from 85% in the first 3 months to <30% after more than 3 months. Bands were detected at 276 bp on ethidium bromide-stained agarose gels after amplification by a nested PCR. The specificity of bands for 32 of 33 samples was proven by hybridization with a GEN-ETI-K-DEIA kit and for a 10 further positive amplicons by sequencing. By using all of these steps to optimize the urine PCR technique, B. burgdorferi infection could be diagnosed by using urine samples from EM patients with a sensitivity (85%) substantially better than that of serological methods (50%). This improved method could be of future importance as an additional laboratory technique for the diagnosis of unclear, unrecognized borrelia infections and diseases possibly related to Lyme borreliosis.

Nicotine withdrawal hyperalgesia and opioid-mediated analgesia depend on nicotine receptors in nucleus accumbens.

The nucleus accumbens, as part of the mesolimbic dopaminergic reward pathway, mediates both addiction to and withdrawal from substances of abuse. In addition, activity of substances of abuse such as opioids in the nucleus accumbens has been implicated in pain modulation. Because nucleus accumbens nicotinic receptors are important in nicotine addiction and because nicotinic activity can interact with opioid action, we investigated the contribution of nucleus accumbens nicotinic receptors to opioid-mediated analgesia/antinociception. The response of the nociceptive jaw-opening reflex to opioids was studied in the rat, both before and during chronic nicotine exposure. In nicotine-naive rats, intra-accumbens injection of the nicotinic receptor antagonist mecamylamine blocked antinociception produced by either systemic morphine, intra-accumbens co-administration of a mu- and a delta-opioid receptor agonist, or noxious stimulation (i.e., subdermal capsaicin in the hindpaw); intra-accumbens mecamylamine alone had no effect. The antinociceptive effect of either morphine or noxious stimulation was unchanged during nicotine tolerance; however, intra-accumbens mecamylamine lost its ability to block antinociception produced by either treatment. Intra-accumbens mecamylamine by itself precipitated significant hyperalgesia in nicotine-tolerant rats which could be suppressed by noxious stimulation as well as by morphine. These results indicate that nucleus accumbens nicotinic receptors play an important role in both opioid- and noxious stimulus-induced antinociception in nicotine-naive rats. This role was attenuated in the nicotine-dependent state. The suppression of withdrawal hyperalgesia by noxious stimulation suggests that pain can ameliorate the symptoms of withdrawal, thus suggesting a possible mechanism for pain-seeking behavior.

The use of enucleation and liquid nitrogen cryotherapy in the management of odontogenic keratocysts.

PURPOSE: This study evaluated the use of enucleation and cryosurgery in the management of odontogenic keratocysts. PATIENTS AND METHODS: This study involved a retrospective review of 26 patients. All of the patients received a combination of enucleation and cryosurgery. Postoperative follow-up consisted of clinical and radiographic examinations. RESULTS: Before enucleation and cryotherapy, 22 of the 26 patients had received previous treatment consisting of enucleation alone. The average time from initial treatment to recurrence was 6.2 years. Twenty-three cases occurred in the mandible, 22 in the posterior (proximal to the canine), and 1 in the anterior mandible. Three cases involved the maxilla. Three of the 26 patients (11.5%) developed a recurrence after treatment. The average time from treatment to recurrence in these 3 patients was 1.6 years (range, 1.2 to 1.9 years). The remaining 23 patients (88.5%) had no evidence of clinical or radiographic recurrence. The average time of follow-up was 3.5 years (range, 2.0 to 10.0 years). CONCLUSIONS: Based on these results, the combination of enucleation and liquid nitrogen cryotherapy may offer patients improved therapy in the management of odontogenic keratocysts.

The course of the temporal branch of the facial nerve in the periorbital region.

PURPOSE: This study identified the terminal temporal and zygomatic branches of the facial nerve as they enter the orbicularis oculi muscle and related these branches to identifiable surface markings. MATERIALS AND METHODS: The temporal and zygomatic branches of the facial nerve were dissected from 5 preserved cadavers (10 sides). The most superior temporal branch entering the orbicularis oculi muscle was identified and related to the lateral canthus of the eye. A vertical line was passed through this point so that the line was equidistant from the nasal tip and chin point. A line perpendicular to the vertical line through the lateral canthus served as the horizontal scale. Vertical and horizontal lines through the lateral canthus were used to establish the anatomic relationship between the lateral canthus and the branch of the temporal nerve entering the orbicularis oculi muscle. RESULTS: The temporal branch was an average of 2.85 +/- 0.69 cm superior to the lateral canthus and an average of 2.54 +/- 0.43 cm lateral to the lateral canthus as it courses into the orbicularis oculi muscle. At the lateral border of the orbicularis oculi muscle, where the temporal and zygomatic nerves insert into the muscle, the mean vertical distance between the temporal and zygomatic nerves was 1.72 +/- 0.62 cm. CONCLUSION: Incisions superior or inferior and parallel to the course of the facial nerve, can provide access to the fronto zygomatic suture and the superior and lateral orbit without damaging its branches.

A financial analysis of maxillomandibular fixation versus rigid internal fixation for treatment of mandibular fractures.

PURPOSE: The aim of this study was to compare the cost-effectiveness of mandibular fracture treatment by closed reduction with maxillomandibular fixation (CRF) with open reduction and rigid internal fixation (ORIF). PATIENTS AND METHODS: This was a retrospective study of 85 patients admitted to the Oral and Maxillofacial Surgery Service at San Francisco General Hospital and treated for mandibular fractures from January 1 to December 31, 1993. The patients were divided into 2 groups: 1) those treated with CRF and 2) those treated with ORIF. The outcome variables were length of hospital stay, duration of anesthesia, and time in operating room. The charge for primary fracture treatment included the fees for the operation and hospitalization without any complications. Within the group of 85 patients treated for mandibular fractures in 1993, 10 patients treated with CRF and 10 patients treated with ORIF were randomly selected, and hospital billing statements were used to estimate the average charge of primary treatment. The average charge to manage a major postoperative infection also was estimated based on the billing statements of 10 randomly selected patients treated in 1992 (5 treated with CRF, 5 with ORIF) who required hospital admission for the management of a complication. The average total charge was computed by using the average charge for primary treatment plus the incidence of postoperative infection multiplied by the average charge for management of that complication. RESULTS: Eighty-five patients were included in the study. The average charge for primary treatment was $10,100 for the CRF group and $28,362 for the ORIF group. The average charge for the inpatient management of a major postoperative infection was $26,671 for the CRF group and $39,213 for the ORIF group. The average total charge for management of a mandible fracture with CRF was $10,927; the total charge for the ORIF group was $34,636. CONCLUSION: The results of this retrospective study suggest that the use of CRF in the management of mandibular fractures at our institution provides considerable savings over treatment by using ORIF. The use of ORIF should be reserved for patients and fracture types with specific indications.

Significance of laboratory findings for the diagnosis of neurosyphilis.

Our objective is to assess the specificity and sensitivity, and thus elaborate the relevance, of different laboratory findings for the diagnosis of neurosyphilis. One hundred and fourteen HIV-negative pairs of serum and cerebrospinal fluid (CSF) samples were examined by the Venereal Disease Research Laboratory (VDRL) test, a fluorescent treponemal antibody-absorption (FTA-ABS) test, microhaemagglutination assay with Treponema pallidum antigen (MHA-TP) test (serum) and Treponema pallidum haemagglutination assay (TPHA) test (CSF); further, albumin, total protein, and total IgG were determined and, in the CSF, cell count was performed. The donors were 60 patients with active neurosyphilis and 54 healthy persons with a former history of syphilis and with persisting positive results in the T. pallidum haemagglutination tests (serum: MHA-TP, CSF: TPHA), who supplied specimens for control. Albumin quotient, IgG index, TPHA index, modified TPHA index, Intrathecally produced T. pallidum Antigen (ITpA) index, its 2 modifications and, in 12 samples, the adenovirus group antibody (AVGA)/TPHA index were ascertained. The specificity and sensitivity of the TPHA index were 100% and 98.3%, of the modified TPHA index 50.0% and 96.7%, of the ITpA index 42.6% and 90.0%, of the modified ITpA indices 51.8% and 68.3% (first modification) and 53.7% and 63.3% (second modification). The AVGA/TPHA index yielded a specificity of 91.7% (11/12). The CSF VDRL test was positive in 55/60 (91.7%) of samples from patients with neurosyphilis and in none of the controls (0/54). A CSF-TPHA titre greater than 1:320 was observed in 59/60 (98.3%) of the neurosyphilis specimens and in none of the controls (0/54). A TPHA index above an outcome of 70, a positive CSF-TPHA test at a titre greater than 1:320 and, with lower sensitivity, the criteria of the Centers for Disease Control (CDC) guidelines yield the most reliable results for laboratory support to a diagnosis of neurosyphilis. The modified TPHA index, the ITpA index, and its 2 modifications produce results of minor sensitivity and poor specificity. Observations on the AVGA/THPA index are too limited yet for judgement. The diagnostic significance of a CSF-TPHA titre above 320 needs further confirmation on a greater number of observations made by different laboratories.