Motor polyradiculoneuropathy as an unusual presentation of neurobrucellosis: a case report and literature review.

Brucellosis, a zoonotic disease caused by Brucella species, poses a significant global health concern. Among its diverse clinical manifestations, neurobrucellosis remains an infrequent yet debilitating complication. Here, we present a rare case of neurobrucellosis with unusual presentations in a 45-year-old woman. The patient's clinical course included progressive lower extremity weakness, muscle wasting, and double vision, prompting a comprehensive diagnostic evaluation. Notable findings included polyneuropathy, elevated brucella agglutination titers in both cerebrospinal fluid and blood, abnormal EMG-NCV tests, and resolving symptoms with antibiotic therapy. The clinical presentation, diagnostic challenges, and differentiation from other neurological conditions are discussed. This case underscores the importance of considering neurobrucellosis in regions where brucellosis is prevalent and highlights this rare neurological complication's distinctive clinical and radiological features. Early recognition and appropriate treatment are crucial to mitigate the significant morbidity associated with neurobrucellosis.

Spinal fluid IgG antibodies from patients with demyelinating diseases bind multiple sclerosis-associated bacteria.

A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of patients with demyelinating diseases (DD). The anti-microbial ELISA assays follow on prior human brain tissue RNA sequencing studies that established multiple sclerosis (MS) microbial candidates. Lysates included in the ELISA panel were derived from Akkermansia muciniphila, Atopobium vaginae, Bacteroides fragilis, Lactobacillus paracasei, Odoribacter splanchnicus, Pseudomonas aeruginosa, Cutibacterium (Propionibacterium) acnes, Fusobacterium necrophorum, Porphyromonas gingivalis, and Streptococcus mutans. CSF responses from patients with demyelinating diseases (DD, N = 14) were compared to those with other neurological diseases (OND, N = 8) and controls (N = 13). Commercial positive and negative control CSF specimens were run with each assay. ELISA index values were derived for each specimen against each of the 10 bacterial lysates. CSF reactivity was significantly higher in the DD group compared to the controls against Akkermansia, Atopobium, Bacteroides, Lactobacillus, Odoribacter, and Fusobacterium. Four of the 11 tested DD group subjects had elevated antibody indexes against at least one of the 10 bacterial species, suggesting intrathecal antibody production. This CSF serological study supports the hypothesis that several of the previously identified MS candidate microbes contribute to demyelination in some patients. KEY MESSAGES: A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of patients with demyelinating diseases, including multiple sclerosis and acute disseminated encephalomyelitis. CSF reactivity was significantly higher in the demyelination group compared to the controls against the bacteria Akkermansia, Atopobium, Bacteroides, Lactobacillus, Odoribacter, and Fusobacterium. Several of the demyelination subjects had elevated antibody indexes against at least one of the 10 antigens, suggesting at least limited intrathecal production of anti-bacterial antibodies. This CSF serological study supports the hypothesis that several of the previously identified MS candidate microbes contribute to demyelination in some patients.

A bacterium lipopolysaccharide that elicits Guillain-Barré syndrome has a GM1 ganglioside-like structure.

There is a strong association between Guillain-Barré syndrome (GBS) and Penner's serotype 19 (PEN 19) of Campylobacter jejuni. Sera from patients with GBS after C. jejuni infection have autoantibodies to GM1 ganglioside in the acute phase of the illness. Our previous work has suggested that GBS results from an immune response to cross-reactive antigen between lipopolysaccharide (LPS) of the Gram-negative bacterium and membrane components of peripheral nerves. To clarify the pathogenesis of GBS, we have investigated whether GM1-oligosaccharide structure is present in the LPS of C. jejuni (PEN 19) that was isolated from a GBS patient. After extraction of the LPS, the LPS showing the binding activity of cholera toxin, that specifically recognizes the GM1-oligosaccharide was purified by a silica bead column chromatography. Gas-liquid chromatography-mass spectrometric analysis has shown that the purified LPS contained Gal, GalNAc, and NeuAc, which are sugar components of GM1 ganglioside. 1H NMR methods [Carr-Purcell-Meiboom-Gill (CPMG), total correlation spectroscopy (TOCSY), and nuclear Overhauser effect spectroscopy (NOESY)] have revealed that the oligosaccharide structure [Gal beta 1-3 GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta] protrude from the LPS core. This terminal structure [Gal beta 1-3GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta] is identical to the terminal tetrasaccharide of the GM1 ganglioside. This is the first study to demonstrate the existence of molecular mimicry between nerve tissue and the infectious agent that elicits GBS.

Neuropathy of gastrointestinal Chagas' disease: immune response to myelin antigens.

Most reports of autoimmune response during infection with the parasite Trypanosoma cruzi have dealt with the cardiomyopathic form of Chagas' disease, but little is known about the mechanisms of tissue damage involved in the gastrointestinal form, which was studied here. Chronically infected patients with a severe gastrointestinal form of Chagas' disease present increased antibody production and proliferative responses to peripheral myelin components, such as myelin basic protein (MBP), which is homologous to the P1 protein fraction of peripheral myelin. T lymphocytes preferentially recognize a region on the MBP molecule (1-30), which suggests that the MBP is a potential target on the peripheral nerve for autoimmune reactions in patients with gastrointestinal lesions resulting from Chagas' disease.

Neuroinvasion by Mycoplasma pneumoniae in acute disseminated encephalomyelitis.

We report the autopsy findings for a 45-year-old man with polyradiculoneuropathy and fatal acute disseminated encephalomyelitis after having Mycoplasma pneumoniae pneumonia. M. pneumoniae antigens were demonstrated by immunohistochemical analysis of brain tissue, indicating neuroinvasion as an additional pathogenetic mechanism in central neurologic complications of M. pneumoniae infection.

Investigation of the Role of Campylobacter Infection in Suspected Acute Polyradiculoneuritis in Dogs.

BACKGROUND: Acute polyradiculoneuritis (APN) is an immune-mediated peripheral nerve disorder in dogs that shares many similarities with Guillain-Barré syndrome (GBS) in humans, in which the bacterial pathogen Campylobacter spp. now is considered to be a major triggering agent. Little information is available concerning the relationship between APN and Campylobacter spp. in dogs. HYPOTHESIS/OBJECTIVES: To estimate the association between Campylobacter spp. infection and APN. Associations with additional potential risk factors also were investigated, particularly consumption of raw chicken. ANIMALS: Twenty-seven client-owned dogs suffering from suspected APN and 47 healthy dogs, client-owned or owned by staff members. METHODS: Case-control study with incidence density-based sampling. Fecal samples were collected from each enrolled animal to perform direct culture, DNA extraction, and polymerase chain reaction (PCR) for detection of Campylobacter spp. In some cases, species identification was performed by sequence analysis of the amplicon. Data were obtained from the medical records and owner questionnaires in both groups. RESULTS: In cases in which the fecal sample was collected within 7 days from onset of clinical signs, APN cases were 9.4 times more likely to be positive for Campylobacter spp compared to control dogs (P < 0.001). In addition, a significant association was detected between dogs affected by APN and the consumption of raw chicken (96% of APN cases; 26% of control dogs). The most common Campylobacter spp. identified was Campylobacter upsaliensis. CONCLUSIONS AND CLINICAL IMPORTANCE: Raw chicken consumption is a risk factor in dogs for the development of APN, which potentially is mediated by infection with Campylobacter spp.

Monoclonal antibodies raised against Guillain-Barré syndrome-associated Campylobacter jejuni lipopolysaccharides react with neuronal gangliosides and paralyze muscle-nerve preparations.

Guillain-Barré syndrome and its variant, Miller-Fisher syndrome, are acute, postinfectious, autoimmune neuropathies that frequently follow Campylobacter jejuni enteritis. The pathogenesis is believed to involve molecular mimicry between sialylated epitopes on C. jejuni LPSs and neural gangliosides. More than 90% of Miller-Fisher syndrome cases have serum anti-GQ1b and anti-GT1a ganglioside antibodies that may also react with other disialylated gangliosides including GD3 and GD1b. Structural studies on LPS from neuropathy-associated C. jejuni strains have revealed GT1a-like and GD3-like core oligosaccharides. To determine whether this structural mimicry results in pathogenic autoantibodies, we immunized mice with GT1a/GD3-like C. jejuni LPS and then cloned mAb's that reacted with both the immunizing LPS and GQ1b/GT1a/GD3 gangliosides. Immunohistology demonstrated antibody binding to ganglioside-rich sites including motor nerve terminals. In ex vivo electrophysiological studies of nerve terminal function, application of antibodies either ex vivo or in vivo via passive immunization induced massive quantal release of acetylcholine, followed by neurotransmission block. This effect was complement-dependent and associated with extensive deposits of IgM and C3c at nerve terminals. These data provide strong support for the molecular mimicry hypothesis as a mechanism for the induction of cross-reactive pathogenic anti-ganglioside/LPS antibodies in postinfectious neuropathies.

Cytomegalovirus infection in the normal host.

CMV mononucleosis often resembles EBV infectious mononucleosis; however, certain features of the history and physical may help to distinguish CMV from EBV. While CMV mononucleosis is usually self-limited, certain laboratory abnormalities may persist for months or years after the patient has recovered. Previous reports on CMV in the non-immunocompromised host have rarely described systemic complications. We have reviewed 10 cases of CMV with systemic manifestations at one institution over a 15-year period. These patients had prolonged fevers (often greater than three weeks) and the diagnosis was often unsuspected during the early part of the illness. While two patients required mechanical ventilation, all patients had self-limiting disease and survived. When CMV is suspected and diagnosed early in the course, numerous diagnostic (and potentially dangerous) tests can be avoided in a viral illness in which prolonged fever is common.

Serologic evidence of Campylobacter jejuni/coli enteritis in patients with Guillain-Barré syndrome.

We performed serologic testing for Campylobacter jejuni in 17 consecutive patients with acute Guillain-Barré syndrome from the Boston, Mass area to compare the frequency of this preceding infection with the high rates reported from other areas of the world. The rate of seropositivity, 18%, was considerable, but it was lower than that reported in Australia. Moreover, all of our patients with definite serologic evidence of infection had severe enteritis before Guillain-Barré syndrome, usually with the organism cultured from stool samples. Campylobacter enteritis is an important antecedent illness for Guillain-Barré syndrome but did not precipitate the disease without enteritis.

Campylobacter diarrhea and Guillain-Barré syndrome.

Four of 106 consecutive patients with acute Guillain-Barré syndrome had preceding bacterial enteritis caused by Campylobacter jejuni. One had a severe illness with axonal damage and poor outcome; three had typical courses with good recovery. Preceding illnesses in the other 102 patients were the following: diarrhea in nine (with negative stool cultures in five), upper respiratory tract infections in 46, hepatitis in six, other infectious illnesses in eight, and none in 33. Eight patients previously reported with Campylobacter associated with Guillain-Barré syndrome, and the serologic and clinical diagnosis of Campylobacter enteritis in this context, are reviewed.

The spectrum of antecedent infections in Guillain-Barré syndrome: a case-control study.

OBJECTIVE: To determine which antecedent infections are specifically associated with the Guillain-Barré syndrome (GBS). BACKGROUND: Infections with many agents have been reported preceding GBS. Some infections are related to specific clinical and immunologic subgroups in GBS. Most agents were reported in case reports and uncontrolled small series of GBS patients only, and their relation to GBS and its subgroups remains unclear. METHOD: A serologic study for 16 infectious agents in 154 GBS patients and 154 sex- and age-matched controls with other neurologic diseases. Acute phase, pretreatment samples were used from clinically well-defined GBS patients. The seasonal distribution of serum sampling in the GBS and control group was the same. RESULTS: Multivariate analysis showed that in GBS patients, infections with Campylobacter jejuni (32%), cytomegalovirus (13%), and Epstein-Barr virus (10%) were significantly more frequent than in controls. Mycoplasma pneumoniae infections occurred more often in GBS patients (5%) than in controls in univariate analysis. Infections with Haemophilus influenzae (1%), parainfluenza 1 virus (1%), influenza A virus (1%), influenza B virus (1%), adenovirus (1%), herpes simplex virus (1%), and varicella zoster virus (1%) were also demonstrated in GBS patients, but not more frequently than in controls. C. jejuni infections were associated with antibodies to the gangliosides GM1 and GD1b and with a severe pure motor form of GBS. Cytomegalovirus infections were associated with antibodies to the ganglioside GM2 and with severe motor sensory deficits. Other infections were not related to specific antiganglioside antibodies and neurologic patterns. CONCLUSIONS: Recent infections with C. jejuni, cytomegalovirus, Epstein-Barr virus, and M. pneumoniae are specifically related to GBS. The variety of infections may contribute to the clinical and immunologic heterogeneity of GBS.

Guillain-Barré and Fisher's syndromes subsequent to Campylobacter jejuni enteritis are associated with HLA-B54 and Cw1 independent of anti-ganglioside antibodies.

The frequencies of human leukocyte antigens (HLA)-class I (A, B and Cw) were determined serologically and those of HLA-class II (DRB1 and DQB1) at the genomic level in 35 Japanese patients with Guillain-Barré syndrome (GBS), 58 with Fisher's syndrome (FS), and 112 healthy controls. HLA-B54 and -Cw1 antigens were found in GBS and FS patients from whom Campylobacter jejuni had been isolated more often than found in the healthy controls. No HLA types were related to GBS or FS as a whole, except for the B54 antigen which often was significant in the entire GBS group. This relation, however, may depend on the high population of C. jejuni-isolate patients in our GBS group. There were no relationships between the frequencies of HLA types and the presence of serum IgG antibodies to GM1, GQ1b, GD1a, or GalNAc-GD1a. Our findings suggest that HLA types are associated with the onset of GBS and FS after C. jejuni enteritis and that the HLA types in distinct GBS and FS subgroups of a single etiological origin need to be examined.

HLA-class II alleles in Guillain-Barré syndrome and Miller Fisher syndrome and their association with preceding Campylobacter jejuni infection.

HLA typing for class II alleles was performed on 97 patients with Guillain-Barré syndrome or Miller Fisher syndrome and compared with 100 controls. There was a significant association between HLA-DQB1*03 and preceding Campylobacter jejuni infection (Pc = 0.05).

Reactivity of serum IgG anti-GM1 ganglioside antibodies with the lipopolysaccharide fractions of Campylobacter jejuni isolates from patients with Guillain-Barre syndrome (GBS).

Campylobacter jejuni (Cj) enteritis is the most frequently recognised infection preceding Guillain-Barre syndrome (GBS) and this combination is commonly associated with anti-GM1 ganglioside (anti-GM1) antibodies. We have examined the hypothesis that the anti-GM1 antibodies represent an immune response against the Cj lipopolysaccharide (LPS). We prepared the LPS fraction from 8 isolates of Cj, 3 from GBS patients with acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 3 from patients with Miller Fisher syndrome (MFS) and 2 from enteritis patients without neurological disease. We looked for IgG antibodies against LPS and GM1 in the serum of 10 GBS and 10 MFS patients, including the patients from whom the Cj had been isolated, and 11 normal control subjects. The highest levels of IgG binding to LPS fractions were found in the GBS patient sera and were with one of the LPS fractions extracted from the C. jejuni isolated from a GBS patient, one from a MFS patient and two Cj isolates from enteritis patients without neurological disease. The level of IgG binding to these LPS fractions was related to the level of IgG anti-GM1 antibody in the serum. Affinity-purified anti-GM1 antibodies showed the same pattern of differential binding to the LPS fractions as the serum from which they were derived. Cholera toxin bound to the same LPS fractions as GBS patients' IgG, the binding of which was blocked by the toxin indicating specific antibody reactivity with a GM1 hapten. The presence of serum anti-GM1 antibodies did not coincide with the presence of the GM1 hapten on the LPS of the infecting strain of Campylobacter indicating that anti-GM1 antibodies do not necessarily arise as part of a simple immune response against the LPS. The IgG antibodies binding to LPS were predominantly of the IgG2 isotype but patients with anti-GM1 IgG had mainly antibodies of IgG1 subclass against both LPS and GM1, implying their production by a T-cell dependent mechanism.

Guillain-Barré syndrome after varicella-zoster infection. Report of two cases.

Two patients developed Guillain-Barré syndrome after varicella-zoster infection; a 4-year-old boy after chickenpox and a 74-year-old man after shingles. Both had decreased CD8-positive lymphocytes in the blood during the course of their illness. These cases and others reported in the literature suggest that varicella-zoster infection is a significant but rare trigger factor of Guillain-Barré syndrome. An alteration in the balance of helper and suppressor lymphocytes may be an important pathogenetic mechanism.

A theory of virus-induced demyelination in the Landry-Guillain-Barré syndrome.

The Landry-Guillain-Barré syndrome (LGBS) is a demyelinating disorder of the peripheral nervous system frequently preceded by infection with common viruses. Most prevalent among these agents are herpesviruses, particularly Epstein-Barr virus (EBV) and cytomegalovirus (CMV). The specific role played by antecedent viral infection in the pathogenesis of the LGBS remains obscure. In this regard, recent studies of Marek's disease (MD) neuropathy, an avian herpesvirus-induced experimental model for the LGBS, may provide insight. The autoimmune pattern of demyelination seen in MD neuropathy is histopathologically indistinguishable from that seen in the LGBS. In this paper, a comprehensive theory is discussed regarding the pathogenetic mechanisms that may be operative in the LGBS.

Prognosis of facial palsy in Borrelia burgdorferi meningopolyradiculoneuritis.

Out of 72 patients treated for Borrelia burgdorferi meningopolyradiculoneuritis facial palsies occurred in 22 (12 unilateral, 10 bilateral). Eleven of the 32 pareses were initially complete. By the follow-up examination patients had recovered well with slight sequelae in 22% without cosmetically disfiguring pareses or synkinesias. Electrophysiological studies revealed axonal damage of the nerve as the underlying mechanism.

Characterization of Campylobacter jejuni isolates from patients with Guillain-Barré syndrome.

Campylobacter jejuni is a major pathogen preceding Guillain-Barré syndrome (GBS), and most C. jejuni isolates from GBS patients belong to Penner serotype 19 (heat-stable; HS-19). We analyzed sixteen independent clinical isolates from GBS patients, twelve of which belonged to HS-19, three to HS-2, and one to HS-4, using PCR-based RFLP analysis of a flagellin-A (flaA) gene. Two isolates from patients with Miller Fisher syndrome (MFS), and 27 from patients with uncomplicated enteritis were also examined. All HS-19 isolates, regardless of GBS, showed an identical pattern (Cj-1) by RFLP typing and were distinguishable from those of the other Penner serogroups. In contrast, HS-2 and HS-4 isolates were divided into several different RFLP groups, suggesting HS-19 strains are genetically distinctive among C. jejuni isolates. A DNA fingerprinting method also failed to detect any specific band pattern for GBS-related C. jejuni isolates. We examined relationships among anti-GM1 antibody titres in the sera of GBS patients, clinical forms of GBS, serotype of C. jejuni, and the presence of GM1-like structures in lipopolysaccharide (LPS) components from C. jejuni isolates by immunoblotting. HS-19 related GBS was significantly associated with elevated anti-GM1 antibody titers in the sera of the patients, but not associated with any clinical pattern of GBS. No significant correlations were found between anti-GM1 antibody and the pattern of disease, or between GBS-related C. jejuni strains and the presence of GM1-like structures. HS-19 strains seem to be unique among C. jejuni isolates, and HS-19-related GBS may provide an excellent model for clarification of the pathogenesis of GBS.

Are Campylobacter curvus and Campylobacter upsaliensis antecedent infectious agents in Guillain-Barré and Fisher's syndromes?

Campylobacter curvus and Campylobacter upsaliensis were isolated from stools of patients with Guillain-Barré (GBS) or Fisher's (FS) syndromes. Whether these microorganisms are pathogens of antecedent diarrhea in GBS and FS is not clear, therefore, we made a serological examination. There were no differences in antibody titer to these organisms among the patients with GBS, FS, and the controls. Some patients had elevated antibodies to the bacteria, but most also had serological evidence of C. jejuni infection. Moreover, the patients from whom C. curvus had been isolated did not have antibodies to the bacterium, indicative that they were healthy carriers of C. curvus or that the isolates were the product of contamination. We conclude that neither C. curvus nor C. upsaliensis is the major agent of antecedent diarrhea in GBS and FS.

Inflammatory sensory polyradiculopathy and reactivated peripheral nervous system infection in a genital herpes model.

To study effects of herpesvirus reactivation on the nervous system, mice with latent genital herpes simplex virus type 2 (HSV-2) infections were immunosuppressed. Reactivated infection was detected by virus isolation or by antigen screening in histological sections of spines that contained cords, roots, and dorsal root ganglia. In ganglia, viral antigen was restricted to 2 distinct groups at T9-L2, and L6-S2 levels. In some ganglia, antigen was found in up to 4% of non-contiguous neurons, in their axons, and in endoneurial and satellite cells. Nerve roots distal to ganglia contained a few antigen-positive endoneurial cells and axons, but convincing antigen was not seen in proximal roots. Rare foci of anterior horn cells in the lower cord were the only central sites found to contain antigen. Comparison of antigen-containing ganglionic neuron counts to vaginal culture data indicate that peripheral virus shedding may depend on the number of neurons with reactivated infection. In non-immunosuppressed, latently infected mice, virus recovery was restricted to ganglionic explants from lower thoracic and lumbosacral regions; these ganglia contained no infectious virus in homogenates and no detectable antigen. These mice had an inflammatory polyradiculopathy in a similar distribution to virus found in latent and reactivated infection. The data show that genital HSV-2 infection can result in more extensive ganglionic latency and peripheral nervous system disease than has previously been recognized. Immunosuppression leads to reactivation and widespread, anatomically restricted antigen expression in many ganglia, consistent with the innervation of the genitourinary tract. Decalcified spine preparations provide a sensitive and simple way to detect virus reactivations and disease in these neural tissues.