Role of fine needle aspiration cytology in nonneoplastic testicular and scrotal lesions and male infertility

OBJECTIVE: To study the role of fine needle aspiration (FNA) in male infertility and in nonneoplastic lesions of the testis and scrotum. STUDY DESIGN: In a retrospective study over a 5-year period, 164 cases of FNA of testicular and scrotal nonneoplastic lesions were retrieved. Aspiration was performed with a 23-gauge needle on a 20-mL syringe. RESULTS: Of 164 cases, 27 (16%) remained inconclusive; they were mainly from epididymal lesions. The remaining 137 cases were categorized as inflammatory lesions, 52 (31.7%); noninflammatory lesions, 42 (25.6%); and infertility cases, 43 (26.2%). Among the inflammatory lesions, 33 cases had nonspecific inflammation, 13 had granulomatous epididymoorchitis, 3 cases were of spermatic granuloma, and 3 cases revealed microfilariae. Noninflammatory lesions included 25 cases of spermatocele, 8 of hematoma/torsion, 5 of hydrocele, 3 of benign epididymal cyst and 1 of calcinosis cutis. Among the patients investigated for infertility, 23 (53%) had normal spermatogenesis, 6 (14%) had Sertoli cells only, 5 (119%) had maturation arrest, 6 (14%) showed hypospermatogenesis, and 3 (7%) showed an atrophic pattern. CONCLUSION: FNA of the testis and scrotum is a simple, quick, minimally invasive and painless outpatient procedure. The sample obtained is more representative than biopsy as several separate punctures can be made, and there is no local scarring.     

Histopathological study on inflammation in cholecystoses

At present, according to the unanimously accepted data, cholecystoses are noninflammatory, nonlithiasic, gallbladder diseases. However the authors' experience has proved that the inflammatory process is much more frequent than it is believed and often associated also with lithiasis, a fact which, in the authors' opinion, would justify a reconsideration of this group of diseases. This study, based on histopathologic examination, was carried out in 1,630 gallbladder specimens, surgically removed. Out of these, 278 (17.05 per cent) were identified as cholecystoses; 156 out of them were cholesteroloses and 122 diverticular diseases of the gallbladder. Inflammation as a well defined morphologic process was found in 104 cases (66.67 per cent) of cholesterolosis and in 119 cases (97.54 per cent) of diverticular disease, therefore 80.21 per cent of the cases of cholecystosis examined were associated with inflammation. As regards lithiasis, it was present in 131 of the cases (46.76 per cent). The inflammatory process presented a chronic aspect with no other particular morphologic characteristics. By correlating the histopathologic data with the clinical evolutive ones, it was observed that the presence of inflammation corresponded with a clinical evolution of the disease of about three years. The authors believed that the group of cholecystoses should be reconsidered bearing in mind that inflammation is present in most of the cases and in almost half of them it is associated with lithiases. Under these conditions the sphere of chronic nonlithiasic, noninflammatory gallbladder diseases becomes considerably reduced today.     

Tissue plasminogen activator-mediated fibrinolysis protects against axonal degeneration and demyelination after sciatic nerve injury

Tissue plasminogen activator (tPA) is a serine protease that converts plasminogen to plasmin and can trigger the degradation of extracellular matrix proteins. In the nervous system, under noninflammatory conditions, tPA contributes to excitotoxic neuronal death, probably through degradation of laminin. To evaluate the contribution of extracellular proteolysis in inflammatory neuronal degeneration, we performed sciatic nerve injury in mice. Proteolytic activity was increased in the nerve after injury, and this activity was primarily because of Schwann cell-produced tPA. To identify whether tPA release after nerve damage played a beneficial or deleterious role, we crushed the sciatic nerve of mice deficient for tPA. Axonal demyelination was exacerbated in the absence of tPA or plasminogen, indicating that tPA has a protective role in nerve injury, and that this protective effect is due to its proteolytic action on plasminogen. Axonal damage was correlated with increased fibrin(ogen) deposition, suggesting that this protein might play a role in neuronal injury. Consistent with this idea, the increased axonal degeneration phenotype in tPA- or plasminogen-deficient mice was ameliorated by genetic or pharmacological depletion of fibrinogen, identifying fibrin as the plasmin substrate in the nervous system under inflammatory axonal damage. This study shows that fibrin deposition exacerbates axonal injury, and that induction of an extracellular proteolytic cascade is a beneficial response of the tissue to remove fibrin. tPA/plasmin-mediated fibrinolysis may be a widespread protective mechanism in neuroinflammatory pathologies.     

Demonstration of T lymphocytes in human blood and cerebrospinal fluid with Helix pomatia A hemagglutinin

Peroxidase-labelled Helix pomatia A hemagglutinin (HPH) was used as a T-cell marker for neuraminidase-treated human lymphocytes from blood or cerebrospinal fluid (CSF). Lymphocytes from the blood of 22 patients with noninflammatory diseases of the central nervous system and from the CSF of 16 patients with noninfectious diseases and 29 patients suffering from meningitis or meningoencephalitis were studied. Most HPH-binding cells were found in normal CSF. The variance in the number of reactive lymphocytes was higher in the CSF from patients with inflammatory diseases than in the other types of samples.     

Inflammatory and Noninflammatory Thyroid Eye Disease: Comparison of Disease Signs,Symptoms, and Quality of Life in Patients in the United States

ObjectiveThyroid eye disease (TED) is an autoimmune, inflammatory disease resulting in retro-orbital fat and extraocular muscle expansion. TED quiets (“inactivates”) as inflammation wanes; however, signs/symptoms often persist. Signs/symptoms of the disease and the impact on quality of life (QoL) were examined in noninflammatory and inflammatory TED.MethodsData of patients with moderate-to-severe TED were collected from treating physicians. Clinical activity score (CAS, 6/7 measures available) was used to classify TED as inflammatory (CAS ≥ 3) or noninflammatory (CAS = 0 or 1). QoL impact was scored as 1 = “not at all impaired” to 7 = “extremely impaired.” Patients with noninflammatory TED were further grouped into longer (>3 years) and shorter (≤3 years) disease courses.ResultsPatients with inflammatory (N = 307) and noninflammatory (N = 281) TED had comparable age (50.0 ± 13.3 years vs 48.3 ± 13.8 years), gender (66% men vs 64% women), TED duration (4.0 ± 4.9 years vs 4.6 ± 5.5 years), and proportion of smokers (15% vs 11%). The most common signs/symptoms of noninflammatory TED included ocular dryness/grittiness (77%), proptosis (56%), excessive tearing (43%), soft tissue edema (42%), conjunctival redness (24%) decreased vision (24%), and eye muscle involvement (22%; 14% had diplopia). All signs/symptoms were less frequently reported in these patients than in those with inflammatory TED. QoL was impacted by noninflammatory TED, although to a lesser degree than the inflammatory disease (3.6 ± 1.5 vs 4.7 ± 1.4). However, mental health issues were similarly reported. Patients with noninflammatory TED with a longer disease course (9.0 ± 6.0 years) had similar QoL impact, mental health diagnoses, and TED signs/symptoms as those with a shorter disease course (1.4 ± 1.0 years).ConclusionThe signs/symptoms of TED often chronically persist long after TED has “quieted,” continuing to impact a patient’s QoL and mental health. These data suggest that moderate-to-severe TED should be thought of as a robust symptomatic chronic disease, regardless of its inflammatory status.     

Metastatic melanoma to the facial nerve

Isolated metastatic malignant melanoma to the facial nerve has never been reported. This presentation illustrates a primary melanoma of the helix of the ear that was treated by excisional biopsy and then wedge resection in 1983. The primary melanoma was Clark's level IV and 1.3 mm in thickness. In 1985, a facial paresis slowly developed. There was no gross evidence of recurrent melanoma in the ear or neck, but CT scan showed a mass in the region of the stylo mastoid foramen. A reoperation of the primary site revealed metastatic melanoma in the facial nerve, expanding it to approximately 10 times its normal size. A composite resection was done for the melanoma, and the paralyzed face was immediately rehabilitated by a masseter muscle transfer. The patient received 6000 rads to this area postoperatively and has remained free of disease to date, having returned to his profession as a dentist. A detailed study of all the specimens indicated that this represented a primary metastasis to the facial nerve.     

Quality of life following parotidectomy for malignant and benign disease

Parotidectomy is performed for benign or malignant tumors and for selected benign inflammatory and autoimmune conditions. Possible associated complications include facial nerve paralysis, pain, loss of sensation, gustatory sweating, and facial scarring. Global quality of life in patients undergoing parotidectomy has not been reported. The implications of facial surgery with the catastrophic potential of facial nerve paralysis may severely affect quality of life. A quality-of-life study was conducted in patients undergoing parotidectomy for benign and malignant diseases to define the significance of associated morbidity and its impact on quality of life. A quality-of-life instrument was specifically created, based on the principles of the University of Washington Quality of Life questionnaire, and mailed to the patients. Questions addressed recognized complications of parotidectomy. Patient group results were compared for age above and below 45 years, sex, benign versus malignant disease, presence or absence of Frey syndrome, and presence or absence of benign pleomorphic adenoma. Forty-six percent of 125 patients meeting the study criteria fully replied to the questionnaire. The global health score was 3.5, corresponding with "good" to "very good." Except for local sensation, which had a score of 50, all other domains scored above 76. Change in appearance, gustatory sweating, and pain were reported by 70 percent, 57 percent, and 30 percent, respectively. Importance attributed to all domains except facial function was low. Pain was encountered significantly less in patients younger than 45 years of age, and scores for appearance were also highly significant in this age group. Postoperative sequelae were noted in the majority of patients. The dominant sequelae were altered sensation, change in appearance, Frey syndrome, and pain. A degree of permanent postoperative facial nerve impairment was reported by 10 patients. Nevertheless, overall, parotidectomy does not seem to severely affect quality of life.     

Estrogen receptor expression in the facial nucleus of adult hamsters: does axotomy recapitulate development?

Testosterone propionate (TP) augments hamster facial motoneuron regeneration following axonal injury by an androgen-mediated mechanism. Although many of the trophic properties of TP are androgenic, TP can be metabolized to estradiol (E). We have recently shown that E administered in supraphysiological doses can also enhance facial nerve regeneration. The mechanism by which E alters nerve regeneration is unknown. The recent discovery of transient estrogen receptor (ER) expression in the developing rat facial motor nucleus (FMN), coupled with the concept that regeneration may recapitulate development, has led to the hypothesis that facial nerve injury may transiently induce expression of ER in the adult hamster FMN or one of its chief afferents, the principal nucleus of the trigeminal nerve (Nu5). In the present study, this hypothesis was tested using steroid hormone autoradiographic procedures. The right facial nerve was injured in castrated or castrated plus TP adult hamsters. A gonadally intact, nonaxtomized group of hamsters was also included to examine constitutive expression of ER in the FMN or Nu5. The paraventricular nucleus of the hypothalamus (PVN; positive control), FMN, and Nu5, were qualitatively and quantitatively examined for the presence of ER. As expected, ER were present in the PVN-positive control in all groups. ER were neither present nor induced with facial nerve injury or TP administration in either the FMN or Nu5. Alternate mechanisms by which E enhancement of facial nerve regeneration without ER might be explained are discussed.     

Normal and abnormal pathfinding of facial nerve fibers in the chick embryo.

Development of the facial nerve was studied in normal chicken embryos and after surgical disruption of ingrowing sensory facial nerve fibers at 38-72 h of incubation. Disruption of facial nerve fibers by otocyst removal often induced a rostral deviation of the facial nerve and ganglion to the level of the trigeminal ganglion. Cell bodies of the geniculate ganglion trailed their deviating neurites and occupied an abnormal rostral position adjacent to the trigeminal ganglion. Deviating facial nerve fibers were labeled with the carbocyanine fluorescent tracer DiI in fixed tissue. Labeled fibers penetrated the cranium adjacent to the trigeminal ganglion, but they did not follow the trigeminal nerve fibers into the brain stem. Rather, after entering the cranium, they projected caudally to their usual site of entrance and proceeded towards their normal targets. This rostral deviation of the facial nerve was observed only after surgery at 48-72 h of incubation, but not in cases with early otocyst removal (38-48 h). A rostral deviation of the facial nerve was seen in cases with partial otocyst removal when the vestibular nerve was absent. The facial nerve followed its normal course when the vestibular nerve persisted. We conclude that disruption of the developing facial pathway altered the routes of navigating axons, but did not prevent pathfinding and innervation of the normal targets. Pathfinding abilities may not be restricted to pioneering axons of the facial nerve; later-developing facial nerve fibers also appeared to have positional information. Our findings are consistent with the hypothesis that navigating axons may respond to multiple guidance cues during development. These cues appear to differ as a function of position of the navigating axon.     

Normal and abnormal pathfinding of facial nerve fibers in the chick embryo

Development of the facial nerve was studied in normal chicken embryos and after surgical disruption of ingrowing sensory facial nerve fibers at 38–72 h of incubation. Disruption of facial nerve fibers by otocyst removal often induced a rostral deviation of the facial nerve and ganglion to the level of the trigeminal ganglion. Cell bodies of the geniculate ganglion trailed their deviating neurites and occupied an abnormal rostral position adjacent to the trigeminal ganglion. Deviating facial nerve fibers were labeled with the carbocyanine fluorescent tracer Dil in fixed tissue. Labeled fibers penetrated the cranium adjacent to the trigeminal ganglion, but they did not follow the trigeminal nerve fibers into the brain stem. Rather, after entering the cranium, they projected caudally to their usual site of entrance and proceeded towards their normal targets. This rostral deviation of the facial nerve was observed only after surgery at 48–72 h of incubation, but not in cases with early otocyst removal (38–48 h). A rostral deviation of the facial nerve was seen in cases with partial otocyst removal when the vestibular nerve was absent. The facial nerve followed its normal course when the vestibular nerve persisted. We conclude that disruption of the devloping facial pathway altered the routes of navigating axons, but did not prevent pathfinding and innervation of the normal targets. Pathfinding abilities may not be restricted to pioneering axons of the facial nerve; later-developing facial nerve fibers also appeared to have positional information. Our findings are consistent with the hypothesis that navigating axons may respond to multiple guidance cues during development. These cues appear to differ as a function of position of the navigating axon. © 1992 John Wiley & Sons, Inc.     

Surgical management of parotid hemangioma

Hemangiomas represent one of the most common childhood neoplasms. They are often managed conservatively, requiring numerous years for spontaneous involution. No effective medical treatment has been reported for children with large, deforming hemangiomas of the parotid gland and overlying cheek. The authors retrospectively studied 17 children who underwent surgical resection of parotid hemangiomas at Childrens Hospital Los Angeles from 1997 to 2003. All 17 patients had improvements in facial asymmetry and deformity. There were no major complications. Minor complications included hematoma (11.8 percent), transient facial nerve palsy (11.8 percent), and blood transfusion (5.9 percent). All operations were performed on an outpatient basis. Surgical resection of parotid hemangiomas provides an aesthetic benefit to young children with low associated morbidity. Early resection by an experienced surgeon should be considered as a treatment option for these disfiguring lesions.     

Fibronectin gene expression in polymorphonuclear leukocytes. Accumulation of mRNA in inflammatory cells

Using a fibronectin cDNA probe, we have studied the accumulation of fibronectin mRNA in polymorphonuclear leukocytes (PMN) in response to inflammation. Nonactivated PMN from human peripheral blood were used as a source of noninflammatory cells and PMN from inflamed knee joints of patients with chronic inflammatory joint disorders (rheumatoid and psoriatic arthritis) were used as a source of inflammatory cells. By dot blot and Northern hybridization analysis, we have found the presence of fibronectin mRNA in these cells. Its size was estimated at approximately equal to 8.7-8.8 kilobases. When noninflammatory PMN were compared to inflammatory PMN in terms of fibronectin mRNA accumulation, a marked increase was found in inflammatory cells (2- to 12.7-fold stimulation). It was also observed that the increased mRNA levels in inflammatory PMN lead to increased synthesis of the protein. These findings establish that PMN are part of the fibronectin-producing cells and that the level of mRNA in these cells is influenced by the inflammatory process.     

Interpreting crosstalk between TNF-alpha and NGF: potential implications for disease

Tumour necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine, whereas nerve growth factor (NGF) is a neurotrophin that can promote neural cell survival, differentiation and maturation. However, recent papers indicate that TNF-alpha has a pivotal role in fate decisions of neural cells in normal noninflammatory conditions, whereas NGF contributes to maintenance of inflammation. Although these observations suggest a close relationship between NGF and TNF-alpha signalling, crosstalk between these factors is not fully understood. In this Opinion article, we review recent reports regarding possible crosstalk between NGF and TNF-alpha and we propose a positive-feedback loop of their expression. We discuss the possible mechanisms by which disturbance of the crosstalk could contribute to diseases such as cancer and Alzheimer's disease.     

Neurovascular free-muscle transfer for the treatment of established facial paralysis following ablative surgery in the parotid region

Neurovascular free-muscle transfer for facial reanimation was performed as a secondary reconstructive procedure for 45 patients with facial paralysis resulting from ablative surgery in the parotid region. This intervention differs from neurovascular free-muscle transfer for treatment of established facial paralysis resulting from conditions such as congenital dysfunction, unresolved Bell palsy, Hunt syndrome, or intracranial morbidity, with difficulties including selection of recipient vessels and nerves, and requirements for soft-tissue augmentation. This article describes the authors' operative procedure for neurovascular free-muscle transfer after ablative surgery in the parotid region. Gracilis muscle (n = 24) or latissimus dorsi muscle (n = 21) was used for transfer. With gracilis transfer, recipient vessels comprised the superficial temporal vessels in 12 patients and the facial vessels in 12. For latissimus dorsi transfer, recipient vessels comprised the facial vessels in 16 patients and the superior thyroid artery and superior thyroid or internal jugular vein in four. Facial vessels on the contralateral side were used with interpositional graft of radial vessels in the remaining patient with latissimus dorsi transfer. Cross-face nerve grafting was performed before muscle transfer in 22 patients undergoing gracilis transfer. In the remaining two gracilis patients, the ipsilateral facial nerve stump was used as the primary recipient nerve. Dermal fat flap overlying the gracilis muscle was used for cheek augmentation in one patient. In the other 23 patients, only the gracilis muscle was used. With latissimus dorsi transfer, the ipsilateral facial nerve stump was used as the recipient nerve in three patients, and a cross-face nerve graft was selected as the recipient nerve in six. The contralateral facial nerve was selected as the recipient nerve in 12 patients, and a thoracodorsal nerve from the latissimus dorsi muscle segment was crossed through the upper lip to the primary recipient branches. A soft-tissue flap was transferred simultaneously with the latissimus muscle segment in three patients. Contraction of grafted muscle was not observed in two patients with gracilis transfer and in three patients with latissimus dorsi transfer. In one patient with gracilis transfer and one patient with latissimus dorsi transfer, acquired muscle contraction was excessive, resulting in unnatural smile animation. The recipient nerves for both of these patients were the ipsilateral facial nerve stumps, which were dissected by opening the facial nerve canal in the mastoid process. From the standpoint of operative technique, the one-stage transfer for latissimus dorsi muscle appears superior. Namely, a combined soft-tissue flap can provide sufficient augmentation for depression of the parotid region following wide resection. A long vascular stalk of thoracodorsal vessels is also useful for anastomosis, with recipient vessels available after extensive ablation and neck dissection.     

Selective myectomy for postparetic facial synkinesis

Synkinetic movements are secondary to facial palsy because they appear like a late sequela to spontaneously healing facial nerve injury. They are produced by an involuntary contraction of a muscle group simultaneous with contraction of other homologous muscle groups. The disorderly regeneration of severed axons is responsible for these movements. According to the Lippschitz theory, the regenerating nerve fibers sprout into the wrong peripheral branches. Between 1975 and 1986, 71 patients with facial paralysis were evaluated. Spontaneous recovery from the facial paralysis occurred in 28 of these patients; 14 (50 percent) developed synkinetic movements, and surgical treatment was sought by only 6 patients. In all patients, the lesion of the facial nerve was in the trunk, proximal to the principal ramification. The most frequent clinical finding was simultaneous activation between the orbicularis oculi and the elevators of the corner of the mouth (12 patients) or the elevators of the upper lip (2 patients). In 8 patients, in whom the slight synkinesis was not noticed by the patients, surgical correction was not necessary, but in the other 6 patients with severe aesthetic disturbances, surgical treatment for "disconnection" of the wrong impulses was realized. I obtained this "disconnection" through resection of the involved perioral muscle groups instead of paralysis of the orbicularis oculi. Follow-up of the 6 patients operated with the surgical treatment proposed herein for between 4 and 8 years has shown good aesthetic results without functional or aesthetic sequelae.     

Prostaglandin activity in human cutaneous inflammation: Detection by radioimmunoassay

A prostaglandin-specific radioimmunoassay capable of detecting 10 pg of PGE₂ is described. Using this assay we were able to demonstrate prostaglandin activity in dermal perfusates from five of eight patients with contact dermatitis and in blister fluid from four volunteers with contact dermatitis and four volunteers with cantharidin blisters. The prostaglandin activity had a definite time relationship to inflammatory activity of the skin. Dermal perfusates from normal skin or psoriatic skin and blister fluid from noninflammatory (suction) blisters were without activity. The data suggest that prostaglandins may be a common denominator in cutaneous inflammation.     

Electron-microscopic analysis of the mouse facial nerve near the geniculate ganglion

An electron-microscopic analysis of the mouse facial nerve near the geniculate ganglion shows that there are, on the everage, 603 more nerve fibers in the portion of the nerve distal to the geniculate ganglion than there are in the part proximal to the ganglion. The average distal increase in the number of unmyelinated fibers is 444 and that in the myelinated fibers is 165. The somatic motor nerve fibers and the parasympathetic fibers in the mouse facial nerve may not contribute to the distal excess. It is possible that the increase in the number of unmyelinated fibers distal to the geniculate ganglion is mainly due to the presence of postganglionic sympathetic fibers in the facial trunk distal to the geniculate ganglion and the greater petrosal nerve. The distal increase in the number of myelinated fibers may be mainly contributed by the sensory fibers.     

Mandibular herpes zoster; with report on the use of cortisone in a case with geniculate ganglion symptoms

Herpes zoster, an acute specific viral infection, occurs more commonly than is generally supposed. It should be differentiated from other diseases involving the ear and skin; it must be considered as a possible etiologic agent in some palsies of the facial, glossopharyngeal or vagal nerves. The type of cephalic herpes zoster should be carefully differentiated; cases involving the "geniculate zone" may be other than "Ramsay Hunt's syndrome." This syndrome is now defined as a herpes zoster eruption of the external ear at the "geniculate zone" with involvement of the seventh or seventh and eighth nerves. The "topognostic" method is the best for determining the level at which the facial nerve has been affected. It is questioned whether there is a single outstanding therapeutic agent for this disease. Cortisone had no apparent therapeutic effect in a case reported herein.     

Annexin A1: a central player in the anti-inflammatory and neuroprotective role of microglia

The brain microenvironment is continuously monitored by microglia with the detection of apoptotic cells or pathogens being rapidly followed by their phagocytosis to prevent inflammatory responses. The protein annexin A1 (ANXA1) is key to the phagocytosis of apoptotic leukocytes during peripheral inflammatory resolution, but the pathophysiological significance of its expression in the CNS that is restricted almost exclusively to microglia is unclear. In this study, we test the hypothesis that ANXA1 is important in the microglial clearance of apoptotic neurons in both noninflammatory and inflammatory conditions. We have identified ANXA1 to be sparingly expressed in microglia of normally aged human brains and to be more strongly expressed in Alzheimer's disease. Using an in vitro model comprising microglial and neuronal cell lines, as well as primary microglia from wild-type and ANXA1 null mice, we have identified two distinct roles for microglial ANXA1: 1) controlling the noninflammatory phagocytosis of apoptotic neurons and 2) promoting resolution of inflammatory microglial activation. In particular, we showed that microglial-derived ANXA1 targets apoptotic neurons, serving as both an "eat me" signal and a bridge between phosphatidylserine on the dying cell and formyl peptide receptor 2 on the phagocytosing microglia. Moreover, inflammatory activation of microglia impairs their ability to discriminate between apoptotic and nonapoptotic cells, an ability restored by exogenous ANXA1. We thus show that ANXA1 is fundamental for brain homeostasis, and we suggest that ANXA1 and its peptidomimetics can be novel therapeutic targets in neuroinflammation.     

Triosephosphate isomerase- and glyceraldehyde-3-phosphate dehydrogenase-reactive autoantibodies in the cerebrospinal fluid of patients with multiple sclerosis

Our previous results revealed that Igs in lesions and single chain variable fragment Abs (scFv-Abs) generated from clonal B cells in the cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) bind to axons in MS brains. To study the axonal Ags involved in MS, we identified the glycolytic enzymes, triosephosphate isomerase (TPI) and GAPDH, using Igs from the CSF and scFv-Abs generated from clonal B cells in the CSF and in lesions from MS patients. Elevated levels of CSF-Abs to TPI were observed in patients with MS (46%), clinically isolated syndrome (CIS) suggestive of MS (40%), other inflammatory neurological diseases (OIND; 29%), and other noninflammatory neurological diseases (ONIND; 31%). Levels of GAPDH-reactive Abs were elevated in MS patients (60%), in patients with CIS (10%), OIND (14%), and ONIND (8%). The coexistence of both autoantibodies was detected in 10 MS patients (29%), and 1 CIS patient (3%), but not in patients with OIND/ONIND. Two scFv-Abs generated from the CSF and from lesions of a MS brain showed immunoreactivity to TPI and GAPDH, respectively. The findings suggest that TPI and GAPDH may be candidate Ags for an autoimmune response to neurons and axons in MS.