Anticorps dans la myasthénie

In autoimmune myasthenia gravis, 75 to 80% of patients have antiacetylcholine receptor antibodies (anti-AChR abs) quantified by immunoprecipitation. Anti-AChR abs are polyclonal, directed against all AChR subunits, with a major fraction against the main immunogenic region, (alpha-subunit, aminoacids 67-76); they cause AChR loss by three mechanisms: blocking of acetylcholine binding; accelerated degradation or AChR due to bridging of two adjacent AChR molecules (antigenic modulation); lysis of postsynaptic membrane induced by complement. Neither anti-AChR ab level nor antigenic repertoire are correlated with disease severity. Studies performed on rat and human myotubes have shown that capacity of myasthenic patients's sera or immunoglobulins to induce AChR loss was correlated with anti-AChR ab titer but not with severity. Highest anti-AChR ab titers are found in young women with hyperplastic thymus, lowest in older patients and atrophic thymus. Ten to fifteen percent of babies born to myasthenic mothers suffer from a transitory neonatal myasthenic syndrome due to passive transfer of maternal anti-AChR abs. There is no correlation between clinical condition of the baby (presence and severity of neonatal myasthenia) and severity of maternal myasthenia. The risk of neonatal myasthenia is high when maternal ab titer is elevated (≥ 100 nM). Very rare and severe cases of foetal neonatal myasthenia gravis with arthrogryposis, hypomobility are due to presence in maternal serum of anti-AChR ab directed against foetal (gamma) AChR. In generalized myasthenia without anti-AChR ab, antibodies directed against MuSK, a postsynaptic molecule involved in AChR aggregation, are detected in around 40% of patients. Features of MuSK+ myasthenia are the following: strong female preponderance, severity (respiratory and bulbar) requiring immunosuppressants, facial and tongue atrophy, poor response to anticholinesterase inhibitors, atrophic thymus and poor response to thymectomy. Low-affinity anti-AChR abs have been recently reported in myasthenia gravis without anti-AChR and anti-MuSK ABS.     

Heterogeneity of immunopathological features of AChR/MuSK autoantibody-negative myasthenia gravis

We compared B cells and germinal centers in thymus from myasthenia gravis (MG) patients either with anti-acetylcholine receptor (AChR) autoantibodies or with neither anti-muscle-specific tyrosine kinase (MuSK) nor anti-AChR (seronegative MG: SN-MG). The numbers and frequencies of total and germinal center B cells varied in the SN-MG thymi, some of which were normal/atrophic. Others were clearly hyperplastic, their B cell parameters overlapping with those in AChR-positive MG, which implicates the thymus in pathogenesis. Indeed, some SN-MG patients apparently benefited from thymectomy, which should be considered a management option.     

Myasthénie séronégative et myasthénie avec anticorps anti-MuSK : une série rétrospective de 20 cas

Introduction

Despite the fact that anti-muscle specific tyrosine kinase (MuSK) antibodies have been discovered for seven years, only a few studies have, until now, focused on myasthenia without acetylcholine-receptors antibodies (ab) (formerly known as “seronegative myasthenia”), and among them, anti-MuSK-antibody-positive and -negative patients.

Method

We retrospectively studied 20 patients with “seronegative” myasthenia gravis, eight of them being anti-MuSK-ab positive, the remaining twelve being negative. We searched for clinical, neurophysiological, and therapeutic differences between the two groups (anti-MuSK-ab positive: anti-MuSK+ versus anti-MuSK-ab negative: anti-MuSK−).

Results

Anti-MuSK+ patients had more predominantly bulbar involvement and had more severe disease (these patients required referral to intensive care more frequently). There was no difference between the two groups concerning treatment efficiency and tolerance. Most of our patients were treated with acetylcholinesterase-inhibitors, and immunomodulatory or immunosuppressive drugs that could indirectly reflect greater severity. However, there was no difference in treatments for anti-MuSK+ versus anti-MuSK− patients.

Conclusion

These results both confirm and complete the preexisting data on RACh-negative myasthenia, and especially on myasthenia associated with MuSK antibodies.     

Clinical delineation of myasthenia gravis in the Kingdom of Bahrain

Objectives:To report demographic and clinical data on 98 myasthenia gravis (MG) patients, seen over 5 years (January 2014-December 2018).Methods:This was a retrospective, observational cohort study carried out at 3 hospitals in Bahrain. MG was classified into ocular or generalized types. We subdivided MG into early-onset (EOMG, ≤ 49 years) or late-onset (LOMG, > 49 years). Demographic and clinical data were recorded. The data was entered and analyzed using SPSS version 26.0.Results:61.2% were females. The mean age at onset was 43.8±17.7 years in males and 43.1±15.7 years in females. 72.4% had EOMG. A pure ocular presentation was most common (51%). Limb weakness was more prevalent in AChR-positive patients. The MuSK group had more severe presentation. 57.1% of patients were AChR-positive, 3.1% MuSK-positive, and 39.8% double-seronegative. Generalized disease onset was more likely with AChR. Abnormal CT chest was seen in 24/69 (35%) including thymic hyperplasia, thymoma, and thymic atrophy. Pathology findings were thymic hyperplasia (55.0%), thymoma (30%), thymolipoma (10%), and normal thymus (5%). Treatment outcomes were favorable.Conclusion:The present study revealed that MG was more common in females, with similar age at onset between males and females. The majority of patients had EOMG with ocular disease and AChR positivity. The clinical outcomes were favorable. Following a standardized protocol for MG diagnosis and workup is recommended.

Myasthenia gravis (MG) is an autoimmune disease of neuromuscular transmission, characterized by fatigable muscle weakness,¹ mediated by an antibody attack on components of the postsynaptic membrane of the neuromuscular junction, such as the acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK) and lipoprotein receptor-related protein 4 (LRP4).^2,3 This may result in various distribution of muscle weakness among different patients, including ocular and limb weakness, bulbar involvement, and sometimes respiratory failure, as well as various degrees of severity.^2,4,5 The MG is the major disorder that affects the neuromuscular junction, while other rarer syndromes include the Lambert-Eaton myasthenic syndrome and botulism, both affecting the presynaptic neuromuscular junction.⁴ The Myasthenia Gravis Foundation of America (MGFA) clinical classification (class I ocular, class II mild generalized weakness, class III moderate generalized weakness, class IV severe weakness, and class V needing intubation) is used to identify subgroups of MG patients sharing certain clinical features or disease severity, which may help predict disease prognosis and treatment outcome.⁶Based on serum antibody profile and clinical phenotypes, MG can be classified into seven subgroups: early-onset MG (EOMG), late-onset MG (LOMG), thymoma-associated MG, MuSK MG, LRP4 MG, ocular MG, and seronegative (SN) generalized MG.^4,5,7 This classification is clinically useful, as there are important differences in terms of clinical features, thymus abnormalities, treatment outcome, and drug adverse events among different phenotypes.^2,5 For example, Deymeer et al⁵ compared the clinical characteristics of 32 anti-MuSK MG, 161 anti-AChR MG and 33 SN MG patients. The MuSK MG group had more bulbar involvement and more severe disease with crises, while the SN group had a milder disease with a good outcome and lower percentage of steroid maintenance doses and use of other immunosuppressants such as azathioprine. Females predominated in all 3 groups.In general, the prognosis of MG is good, due to early diagnosis and availability of symptomatic treatment, and the use of effective immunosuppressants and other supportive measures.⁴ The aim of our study was to retrospectively gather data on the clinical characteristics of MG patients in the Kingdom of Bahrain, and compare it with regional and international data.     

Clinical comparison of anti-MuSK- vs anti-AChR-positive and seronegative myasthenia gravis

We compared 65 anti-acetylcholine receptor (AChR)-negative myasthenia gravis (MG) patients, including 32 anti-muscle-specific tyrosine kinase (MuSK)-positive (49%) and 33 anti-MuSK-negative (seronegative) (51%) patients, with 161 anti-AChR-positive MG patients. The anti-MuSK-positive group had a higher frequency of bulbar involvement and respiratory crises. The seronegative group was in between the anti-MuSK positive and the anti-AChR positive groups, being closer to the latter, with regard to the severity of the disease. At the end of follow-up, the outcome of the anti-MuSK-positive patients was not different from that of the anti-AChR-positive patients, although their maintenance corticosteroid dose was higher. The seronegative patients had better outcome than the other two groups.     

New insights in heparin-induced thrombocytopenia by the use of fluid-phase assays to detect specifically platelet factor 4/heparin complex antibodies and antibody-secreting cells

Introduction

The key feature of heparin-induced thrombocytopenia (HIT) is the production of antibodies (Ab) against the platelet factor 4 (PF4)/heparin complex. These Ab are directed against neoepitopes of the PF4 tetramer, which are induced by the complex formation with heparin. To study this humoral immune response in greater detail, either in a murine immunization model or in human blood samples, reliable and specific immune assays to detect specifically Ab against the PF4/heparin complexes, but not PF4 alone are required.

Materials and Methods

We established fluid-phase enzyme-immunoassays in which the soluble biotinylated antigen, PF4/heparin, is firstly captured by specific Ab, and secondly directly detected with enzyme-conjugated streptavidin.

Results

The use of this fluid-phase principle allowed a higher specificity than the traditional solid-phase enzyme-immunoassays in terms of Ab binding to murine PF4/heparin compared to murine PF4 alone. This fluid-phase approach applied to the detection of specific murine PF4/heparin Ab-secreting cells (ASC) identified the spleen as the main lymphatic organ that contributes to the PF4/heparin Ab response in mice. IgG ASC specific for PF4/heparin are very transiently detectable in mice, which might explain why anti-PF4/heparin IgG Ab typically disappear within 100 days in humans. Furthermore, this fluid-phase approach was successfully transferred to detect human PF4/heparin-specific Ab.

Conclusion

The fluid-phase principle for the specific detection of anti-PF4/heparin IgG and IgM Ab enables new and improved assays for HIT research in men and mice. At least in mice PF4/heparin antibodies are produced by transient B cells.     

Seronegative myasthenia gravis: disease severity and prognosis

Around 10-20% of myasthenia gravis (MG) patients do not have acetylcholine receptor (AChR) antibodies (seronegative), of whom some have antibodies to a membrane-linked muscle specific kinase (MuSK). To examine MG severity and long-term prognosis in seronegative MG compared with seropositive MG, and to look specifically at anti-AChR antibody negative and anti-MuSK antibody negative patients. Seventeen consecutive seronegative non-thymomatous MG patients and 34 age and sex matched contemporary seropositive non-thymomatous MG controls were included in a retrospective follow-up study for a total period of 40 years. Clinical criteria were assessed each year, and muscle antibodies were assayed. There was no difference in MG severity between seronegative and seropositive MG. However, when thymectomized patients were excluded from the study at the year of thymectomy, seropositive MG patients had more severe course than seronegative (P < 0.001). One seropositive patient died from MG related respiratory insufficiency. The need for thymectomy in seronegative MG was lower than in seropositive MG. None of the seronegative patients had MuSK antibodies. This study shows that the presence of AChR antibodies in MG patients correlates with a more severe MG. With proper treatment, especially early thymectomy for seropositive MG, the outcome and long-term prognosis is good in patients with and without AChR antibodies.     

Generalization after ocular onset in myasthenia gravis: a case series in Germany

Background and purpose

Approximately, 50% of myasthenia gravis (MG) patients initially present with purely ocular symptoms. Of these, about 60% will develop secondary generalized MG, typically within 2 years. Risk factors for secondary generalization are still controversial. In this study, we reviewed clinical parameters, thymic pathologies and medical treatments of MG patients with purely ocular symptoms at onset to investigate risk factors for secondary generalization.

Methods

In this monocentric retrospective study, we reviewed consecutive patients who underwent robotic thymectomy between January 2003 and October 2017 in Charite Universitaetsmedizin Berlin. We used univariate and multivariate Cox proportional hazards regression models to identify factors associated with secondary generalization. Survival curves were plotted using Kaplan–Meier method and log-rank tests were performed to analyze the association between corticosteroids use and secondary generalization in subgroups defined by anti-AChR antibody status and thymic pathology.

Results

One hundred and eighty of 572 MG patients who underwent robotic thymectomy were eligible for inclusion, of whom 110 (61.1%) developed a secondary generalized MG over a mean follow-up time of 23.6 months. The presence of a thymoma (HR 1.659, 95% CI (1.52–2.617), P?=?0.029) was the only risk factor for secondary generalization in our series. Treating with corticosteroids was associated with a lower conversion rate in ocular myasthenia patients with thymic hyperplasia (n?=?55, P?=?0.028), but not with other thymic pathologies including thymoma and normal or atrophic thymus.

Conclusions

The conversion rate in ocular myasthenia was high in our series, predicted by the presence of a thymoma. Our findings suggest that corticosteroids can prevent secondary generalization in ocular myasthenia patients with thymic hyperplasia, which requires further research.

     

The features of myasthenia gravis with autoantibodies to MuSK

OBJECTIVES: To determine if myasthenia gravis (MG) with antibodies to MuSK is a distinct subgroup of seronegative MG. METHODS: We assayed antibodies to muscle specific tyrosine kinase (MuSK) in 55 MG patients who had no antibodies to acetylcholine receptors and looked for the specific phenotype, comparing clinical features of anti-MuSK positive and anti-MuSK negative MG patients. RESULTS: MG with anti-MuSK antibodies was characterised by a striking prevalence of female patients (15 women, two men). Age at onset ranged from 22 to 52 years, with 70.6% of patients presenting at < 40 years of age. The majority of patients (82.4%) had prevalent involvement of facial and bulbar muscles. One third of them did not respond well to anticholinesterase drugs. Steroid immunosuppression was effective in eight patients (44.4%). Nine patients underwent thymectomy; six of these had no thymus pathology, while three had a hyperplastic thymus. At the end of the observation period, six (35.3%) patients were in remission, five (29.4%) improved, four (23.6%) did not change, and two (11.7%) had died. CONCLUSIONS: MG patients with antibodies to MuSK have characteristic clinical features that are different from features of the remaining seronegative MG patients. This emphasises the predictive value of anti-MuSK antibody analysis in seronegative MG patients.     

Clinical and serological study of myasthenia gravis in HuBei Province, China

Background

Ocular and childhood myasthenia gravis (MG) cases seem relatively more common in Oriental than in Caucasian populations, but there have been no comprehensive serological studies on patients from mainland China.

Methods

391 unselected patients with MG attending Tongji Hospital in WuHan (the largest hospital in the province of HuBei, China) were studied during a 15‐month period; most had already received treatment for their condition.

Results

The male to female ratio was 0.8. 50% of the patients were children (<15 years), and age at onset showed a single peak at between 5 and 10 years of age. 64% of the children and 66% of the adults were positive for acetylcholine receptor (AChR) antibodies but the antibody titres were lower than in similar Caucasian studies, although this was partly due to the high incidence of ocular MG. Of the 43 patients with generalised MG without AChR antibodies, only 1 had muscle‐specific kinase antibodies (2.5%) and 2 had voltage‐gated calcium channel antibodies indicating probable Lambert–Eaton myasthenic syndrome. 75% of the children, compared with only 28% of the adults, had ocular MG. Thymoma was evident by MRI in 1.5% of children and in 20% of adults. Despite most patients having received prednisone, very few had obtained full clinical remission.

Conclusion

This study emphasises the frequency of early childhood onset with ocular symptoms and shows that many of these patients have AChR antibodies. By contrast, patients presenting in later age seem to be very uncommon in comparison with recent studies in Caucasian populations.Myasthenia gravis (MG) is the most common primary disorder of neuromuscular transmission. Acetylcholine receptor (AChR) antibodies are present in sera from 80% to 90% of patients with generalised MG, about 50% from those with pure ocular MG and infrequently in healthy people.¹ The remaining 10–20% of generalised patients with MG are AChR antibody negative (seronegative MG, SNMG). IgG autoantibodies to the muscle‐specific kinase (MuSK) were first identified in 70% of patients with generalised SNMG.² However, subsequent reports have found a variable prevalence in different countries, with a low proportion of MuSK antibody‐positive MG in one study from Taiwan³ (reviewed in Vincent and Liete⁴).A number of studies indicate that MG in Oriental populations may be clinically different from that in Caucasians.^5,6,7,8 In particular, paediatric cases are frequent in China, Taiwan and Japan and purely ocular MG is relatively common in children. Since there are also differences in human leucocyte antigen associations between Japanese, Chinese and Caucasian populations,^9,10,11,12 these observations may provide clues to the immunopathogenesis of MG.However, there have been no comprehensive studies of AChR and MuSK antibodies in patients from mainland China. Here, we studied the histories and serology of 391 Chinese patients attending a major hospital in WuHan, China.     

Repetitive nerve stimulation of facial muscles in MuSK antibody-positive myasthenia gravis

To better define electrophysiological abnormalities in myasthenia gravis (MG) patients with muscle-specific tyrosine kinase (MuSK) antibodies (Ab), we compared electrophysiological features of 14 MuSK Ab-positive, 73 acetylcholine receptor antibody (AChR Ab)-positive, and 22 MuSK and AChR Ab-negative (seronegative) patients with generalized disease. Repetitive nerve stimulation (RNS) abnormalities were observed in 86% of MuSK Ab-positive and 82% of AChR Ab-positive patients but in only 55% of seronegative patients. RNS decrements in the orbicularis oculi were more common and severe in the MuSK Ab-positive patients than the other two groups. Single-fiber electromyography (SFEMG) of the extensor digitorum communis was abnormal in 90% of MuSK Ab-positive patients. The high frequency of RNS abnormalities in facial muscles in the MuSK Ab-positive population reflects the propensity for facial muscle involvement in this form of MG and emphasizes the importance of including facial muscles in RNS protocols when evaluating these patients.     

Is excitation–contraction coupling impaired in myasthenia gravis?

OBJECTIVE: To investigate whether excitation-contraction (E-C) coupling of muscle is impaired in patients with myasthenia gravis (MG). METHODS: In 51 patients with generalized MG and 35 normal subjects, compound muscle action potentials (CMAPs) of the abductor pollicis brevis, and movement-related potentials using an accelerometer placed at the thumb tip were simultaneously recorded after median nerve stimulation at the wrist. The E-C coupling time (ECCT) was estimated by a latency difference between CMAP and movement-related potential. Antibodies against acetylcholine receptor (AChR), ryanodine receptor (RyR), and muscle specific receptor tyrosine kinase (MuSK) were measured by immunoassays. RESULTS: The mean ECCT was significantly longer in patients with MG (mean+/-SEM; 2.79+/-0.1 ms; p=0.002) than in normal controls (2.52+/-0.1 ms). Among MG patients, the mean ECCT was longer for patients with thymoma than for those without it (P=0.04), and was shorter for patients treated with FK506 (an immunosuppressant and also an enhancer of RyR related Ca(2+) release) than for those not receiving this treatment (p=0.04). ECCT had no significant correlation with anti-AChR, anti-RyR, or anti-MuSK antibodies. CONCLUSIONS: In MG, E-C coupling appears to be impaired, particularly in patients with thymoma, and FK506 possibly facilitates E-C coupling. SIGNIFICANCE: The functional implication of impaired E-C coupling is not established, but it may contribute to muscle weakness in patients with MG.     

Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts

Introduction: Myasthenia gravis (MG) patients with autoantibodies to muscle‐specific tyrosine kinase (MuSK) represent a distinct subset of those with this disease. Treatment and outcomes data in these patients are limited and conflicting. Methods: We reviewed 110 MuSK‐MG patients from two large clinics in Italy and the USA. Results: Thirty‐nine to 49% of patients with generalized, acetylcholine receptor antibody (AChR‐Ab)–negative MG had MuSK‐MG. Eighty‐five percent were female, with disease onset typically in the fourth decade. Ocular and/or bulbar symptoms were present at onset in 79% of those studied. Eighty‐five percent were MGFA class III or greater, and crisis occurred in 28%. Plasma exchange (PLEX) produced improvement in 93%, whereas only 61% improved after intravenous immunoglobulin. Long‐term outcomes were comparable to those of patients with AChR‐Ab–positive MG. Conclusions: MuSK‐MG has a marked female predominance with frequent oculobulbar weakness and crises. Many patients deteriorate rapidly early in the disease, and PLEX is usually the preferred treatment. Long‐term outcomes are similar to those of patients with AChR‐Ab⁺ MG. Muscle Nerve 44: 36–40, 2011     

Epidemiological and immunological profile of muscle-specific kinase myasthenia gravis in Greece

Objectives:  The purposes of this study were to determine the epidemiological characteristics of muscle-specific kinase-myasthenia gravis (MuSK-MG) in Greece and the IgG subclass of the anti-MuSK antibodies.
Methods:  This population-based study was performed on MuSK-MG patients in Greece between 1 January 1986 and 30 June 2006. Epidemiological and clinical data for 33 patients were collected. In addition, the distribution of anti-MuSK IgG autoantibody subclasses in the sera of 14 patients was determined by immunoprecipitation.
Results:  The average annual incidence was 0.32 patients/million population/year. On 1st July 2006, there were 33 prevalent cases, giving a point prevalence rate of 2.92/million (women 4.56 and men 1.25). In females, onset of MuSK-MG occurred after the age of 30, whilst, in males, the disease appears in any decade. The female:male incidence ratio was 3.33:1, whilst the prevalence ratio was 3.65:1. Most patients presented with involvement of the facial and bulbar muscles. Amongst about 800 MG patients seropositive for antibodies against either the AChR or MuSK, one patient was found to be seropositive for anti-MuSK antibodies and ambiguous for anti-acetylcholine receptor (anti-AChR) antibodies. The vast majority of anti-MuSK antibodies were IgG4, whilst total IgG4 levels in these patients were similar to those in two healthy controls.
Conclusions:  The incidence and prevalence of MuSK-MG in Greece are amongst the highest reported previously for other countries. MuSK-MG in Greece affects both sexes, but mainly females. The main epidemiological indices were calculated. The vast majority of anti-MuSK antibodies were IgG4.     

AChR myasthenia gravis switching to MuSK or double antibody positive myasthenia gravis in two children and literature review

Muscle–specific tyrosine kinase antibody (MuSK–Ab) and acetylcholine receptor antibody (AChR–Ab) coexistence in myasthenia gravis (MG) is very rare. In this report, two children with AChR–Ab switching to double antibody positive MG (DP–MG) or MuSK–Ab positive MG (MuSK–MG) are described. Six similar cases were found in the literature via online database search. Therefore, this study describes eight patients in total, six female and two male. The average age of onset was 7.25 ± 5.95 years. Four AChR–MG patients switched to DP–MG with no known precipitating factor and four switched after thymectomy (two to MuSK–MG and two to DP–MG). After the serological switch, the patients transitioned to the phenotype of MuSK–MG and responded poorly to cholinesterase inhibitors and well to corticosteroids and plasma exchange.     

Comparison of the histological and immunohistochemical features of the thymus in young- and elderly-onset myasthenia gravis without thymoma.

We performed histological and immunohistochemical analyses of the removed thymuses from 20 elderly (onset age > 60 years) and 23 young (onset age < 40 years) patients with myasthenia gravis (MG) who tested positive for serum anti-acetylcholine receptor (AChR) antibodies, but who did not have associated thymoma. In the elderly group, nine (45%) patients had accumulations of lymphocytes, indicating an atrophied thymus with loss of the basic structure. The elderly MG patients with atrophied thymic tissues had higher titres of anti-AChR antibody (59.6+/-81.0 nmol/L) than those with adipose infiltration of the thymus alone (20.1+/-20.9 nmol/L). In immunohistochemical studies using image analysis, both young patients and elderly patients with atrophied thymic tissues were found to have significantly higher levels of CD20 than age-matched controls (p < 0.005). Atrophied thymic tissues, often seen immunohistochemically in young MG patients, may also be found in elderly patients, particularly in those with high titres of the anti-AChR antibody, even though adipose infiltration is marked in these patients.     

Anti-acetylcholinesterase antibodies associate with ocular myasthenia gravis

In MG, anti-AChR or anti-MuSK abs impair neuromuscular transmission. Partial inhibition of AChE can ameliorate symptoms, while a complete block causes a cholinergic blockade. We found anti-AChE abs in 115/240 MG patients, with no correlation with sex, age at onset, thymus pathology, presence of anti-AChR or anti-MuSK antibodies. We found a correlation with the ocular form of the disease, and with milder forms of MG not requiring immunosuppressants; moreover, when we considered only those patients who were off AChEI therapy, we found that ocular patients were positive for anti-AChE abs, while generalized patients were negative. According to an experimental model, we hypothesize that anti-AChE abs could contribute to ptosis through an inhibition of the sympathetic innervation of the tarsal muscle.     

Neurological complications of miliary tuberculosis

Introduction

The symptomatic central nervous system involvement is often seen in patients with miliary tuberculosis.

Materials and methods

In this study, we evaluated 60 consecutive miliary tuberculosis patients, who presented with some neurological manifestations. Evaluation included neurological examination, a battery of blood tests, HIV serology, sputum examination, cerebrospinal fluid (CSF) examination along with imaging of the brain and spinal cord. The patients were followed up after completion of 6 months of antituberculous treatment.

Results

Patients ranged between 14 and 53 years in age. Three patients tested HIV positive. Forty-eight (80%) patients had tuberculous meningitis. In 12 (20%) patients, the CSF examination was normal. In 27 patients with tuberculous meningitis, neuroimaging revealed intracerebral tuberculoma. Fourteen patients showed multiple tuberculomas, while 7 had a solitary tuberculoma. In six patients, the tuberculomas were small and numerous. In two patients, neuroimaging revealed a spinal tuberculoma. For three patients with tuberculous brain masses, the CSF was normal. Nine (15%) patients presented with myelopathy. Three patients exhibited Pott's paraplegia. Three patients had transverse myelitis (with normal neuroimaging). In three patients, the spinal MRI revealed an intramedullary tuberculoma. On follow-up, 15 (25%) patients expired. Thirty-one (52%) patients showed significant improvement. Eight patients (13%) showed nil or partial recovery. Six of the patients with no improvement developed vision loss. Six (10%) patients were lost to follow up.

Conclusion

A variety of neurological complications were noted in military tuberculosis patients, tuberculous meningitis and cerebral tuberculomas being the most frequent complications. However, a majority of patients improved following antituberculous treatment.     

Anti-neuroblastoma antibodies in myasthenia gravis: clinical and immunological correlations

Forty-four of 109 myasthenia gravis (MG) patients (40%) had serum antibodies against human neuroblastoma cells (NBL). Anti-NBL antibodies were most frequent in the sera of MG patients who had either a hyperplastic thymus or a thymoma, clinically mild to moderately severe generalized MG, and a long disease duration (greater than or equal to 11 years). No correlation between individual anti-NBL antibody and anti-acetylcholine receptor (AChR) antibody titers was observed. Seven of the 19 patients negative for anti-AChR antibodies (37%) had anti-NBL antibodies in their sera. These findings provide further evidence for immunological heterogeneity in MG. In addition to the typical autoantibodies to the AChR, autoimmunization against neural antigens can frequently be detected in these patients.     

Elevated titers of anti-thyroperoxidase antibodies in patients with multiple system atrophy: A pilot study

Objectives

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by progressive neuronal loss and alpha-synuclein deposition in oligodendroglial cells in the central nervous system. The cause of MSA remains essentially unknown. A cerebellar syndrome was associated with autoimmune thyroid disease in some cases, apparently not related to MSA and was partially responsive to immunomodulatory therapy.

Patients and methods

28 euthyroid patients who fulfilled the diagnostic criteria for probable MSA, 11 with MSA-cerebellar type (MSA-C), 17 with MSA-parkinsonian type (MSA-P), 28 patients with Parkinson's disease (PD) and 26 normal euthyroid controls were tested the for serum levels of anti-thyroperoxidase antibodies (anti-TPO) and anti-thyroglobulin (Anti-TG) antibodies (Ab).

Results

The laboratory results were statistically similar in all three groups, but 3 MSA-C patients had highly elevated anti-TPO Ab titers.

Conclusion

We identified the presence of elevated anti-TPO levels in a small subgroup of MSA-C patients but neither in MSA-P or PD patients nor in healthy controls. These findings may suggest an autoimmune etiology in some cases of MSA-C.