Acute myelitis with hyperIgEaemia and mite antigen specific IgE: atopic myelitis

An occurrence of acute localised myelitis was recentlyseen in four adult patients with atopic dermatitis who hadhyperIgEaemia and mite antigen specific IgE. The total and mite antigenspecific IgE was therefore studied in serum samples from 19 consecutive patients with acute localised myelitis of unknown aetiology, 56patients with clinically definite multiple sclerosis, and 40 healthy controls. The total IgE concentration was significantly higher in acutelocalised myelitis (median=360 U/ml) than in multiple sclerosis(median=52 U/ml, p<0.0001) and the controls (median=85 U/ml,p=0.0002). The specific IgE to Dermatophagoidespteronyssinus was found more often in patients with acutelocalised myelitis (95%) than in patients with multiple sclerosis(34%, p<0.0001) and the controls (35%, p<0.0001) and the specificIgE to Dermatophagoides farinae was similar (acutelocalised myelitis 79%, multiple sclerosis 29% (p<0.0001), controls30%, (p=0.0003). Atopic dermatitis coexisted more commonly in patientswith acute localised myelitis (37%) than in patients with multiplesclerosis (0%, p<0.0001) and the controls (7.5%, p=0.0089).Therefore, acute localised myelitis with hyperIgEaemia, in which atopyto mite antigens seems to exist, may be a distinct subtype of allergicmyelitis—that is, atopic myelitis.

     

DPB 1 *0501-associated opticomyelitis and atopic myelitis: novel disease entities]

To clarify the relationship between Th 1/Th 2 balance and clinical features, we studied the intracellular IFN gamma-positive versus IL-4-positive cell ratio in peripheral blood CD 4 T cells by flow cytometry and measured total and allergen-specific IgE by ELISA in 227 patients with various neurologic diseases including multiple sclerosis (MS), myelitis and HAM/TSP, and 42 healthy hospital subjects. The intracellular IFN gamma/IL-4 ratio in the patients with acute myelitis was significantly decreased, and the total serum IgE level and frequency of mite antigen-specific IgE were significantly elevated as compared with the controls. Patients with HAM/TSP, however, had a significantly higher intracellular IFN gamma/IL-4 ratio, lower total IgE level, and lower frequency of cedar pollen-specific IgE than did the controls. The patients with recurrent opticomyelitis (ROM) had a significantly higher frequency of relapse, higher EDSS score, and lower number of brain MRI lesions than the patients with conventional MS, and only those with ROM showed a significant association with the HLA-DPB 1 *0501 allele. The ROM patients had a significantly higher intracellular IFN gamma/IL-4 ratio and IL-4-/IFN-gamma + cell percentages than the controls. These findings suggest that the Th 2 cell response predominates in acute myelitis with hyperIgEaemia (atopic myelitis), whereas the Th 1 cell response predominates in ROM and HAM/TSP.     

Acute transverse myelitis with normal brain MRI

Objective To investigate the long-term risk of developing MS in patients presenting with acute transverse myelitis (ATM) and normal brain MRI scans at onset. Methods We studied 58 ATM patients with normal brain MRI at presentation for up to 5 years with serial neurologic and imaging studies. All patients underwent CSF analysis at onset which was defined positive if two or more IgG oligoclonal bands and/or elevated IgG index were present. Brain and spinal cord MRI scans were obtained every 6 months for the first 2 years, and annually thereafter unless the patient experienced a second neurologic attack different from the initial episode to confirm CDMS or there was demonstration of MRI lesions confirming dissemination in time and space to fulfill McDonald imaging criteria to diagnose MS. Results Seventeen of 58 (29%) patients developed MS of which 7 (41%) patients developed CDMS and 10 (59%) developed MS using McDonald Imaging Criteria. Mean time to CDMS by a second clinical attack was 11. 1 months compared to 19. 2 months by MRI lesions (P = 0. 03). None of the patients developed MS after 24 months of onset. All 17 patients who developed MS had positive CSF although 15 patients who had positive CSF did not develop MS during the 5 years of follow-up. Conclusions The majority of patients with ATM and normal brain MRI do not develop MS after 5 years of follow-up confirming the relatively low risk compared to patients with abnormal brain MRI scans. CSF is helpful in distinguishing patients more likely to develop MS. Compared to clinical attacks, serial imaging may not lead to an earlier diagnosis in ATM patients with normal brain MRI.     

Is atopic dermatitis a risk factor for intervertebral disc degeneration? A preliminary clinical and MRI study

Atopic dermatitis (AD) is a common allergic disease that has recently been reported to be complicated with acute myelitis. To clinically evaluate the occurrence of myelitis in AD, 65 consecutive AD patients were neurologically examined. Of these, 37 underwent cervical MRI scans. Unexpectedly, the neurologic and MRI findings did not suggest myelitis, but rather, in most cases, cervical spondylosis. Therefore, we assessed the relationship between AD and cervical spondylosis. In addition, cervical MRI findings in 26 patients with multiple sclerosis (MS) and in 12 normal controls were also evaluated. The neurologic examinations in the AD patients frequently showed hyperreflexia in the legs, and sensory and motor disturbances were often present in the limbs. Cervical MRI findings suggestive of spondylosis, such as intervertebral disc degeneration and bulging/protrusion, were found more frequently in AD patients than in MS patients, with statistical significance. Posterior spondylolisthesis was observed with higher frequency in AD and MS patients than in normal controls. We concluded that AD might be a risk factor for intervertebral disc degeneration. As far as we know, this is the first paper describing the potential association between disc degeneration and AD.     

Case of atopic myelitis with acute onset and atypical distribution of spinal cord lesions]

A 23-year-old woman was admitted to our department because of gait disturbance, sensory impairment in the lower limbs, and sphincter disturbance, all of which had been developing within 24 hours before admission. Neurological examination disclosed symmetric muscle weakness, sensory impairment, and diminished tendon reflexes in the lower limbs. The urinary bladder was hypoactive, and the anal tone was reduced. The spinal cord MRI performed on the day of admission revealed swelling of the epiconus. The CSF findings were not remarkable, except for the elevated levels of IgE (8 IU/ml) and MBP (7.8 ng/ml). Besides, there was a marked increase in the serum mite-specific IgE titers. Collectively, we made a diagnosis of atopic myelitis. She was treated with steroid pulse therapy and plasma exchange, which led to a significant amelioration of her neurological manifestations. The repeat MRI carried out on the 21st day of her admission displayed several foci scattered in the lumbar and sacral spinal cord segments, which exhibited high intensity signals on the T2-weighted images. The values of IgE and albumin in the CSF and serum raised the possibility of intrathecal IgE synthesis. We measured her CSF IgE levels at several time points during admission. The temporal profile of her CSF IgE levels was not correlated with that of her neurological disabilities.     

HLA-DPB1*0201 is associated with susceptibility to atopic myelitis in Japanese

To determine the relationship between susceptibility to atopic myelitis (AM) and polymorphisms of the human leukocyte antigen (HLA)-DPB1 and -DRB1 alleles, we compared each phenotype frequency between 55 AM patients and 367 unrelated healthy controls in Japan. The HLA-DPB1*0201 allele was significantly more frequent in AM patients than in healthy controls (54.5% vs. 31.9%, corrected P value=0.0150, odds ratio=2.564, 95% confidence interval=1.444-4.554). Our result suggests that the immunogenetic background of AM differs from that of other CNS autoimmune diseases, such as multiple sclerosis and neuromyelitis optica, which show distinct HLA class II associations.     

Spinal cord lesions of myelitis with hyperIgEemia and mite antigen specific IgE (atopic myelitis) manifest eosinophilic inflammation

We report the neuropathological findings of spinal cord specimens obtained from two patients who had localized myelitis with hyperIgEemia and mite antigen specific IgE (atopic myelitis). Both cases showed mild spinal cord dysfunction, and the gadolinium-enhanced area of the isolated spinal cord lesion observed on MRI was biopsied, respectively. Neuropathologically, both cases showed many perivascular lymphocyte cuffings associated with disrupted vessels, and the infiltration of eosinophils in the spinal cord lesions. Both myelin and axons were lost in the lesions, which were associated with astrogliosis. These findings suggest that an allergic mechanism may play a role in this condition.     

Magnetic resonance imaging findings in 22 cases of myelitis: comparison between patients with and without multiple sclerosis

We reviewed the magnetic resonance imaging (MRI) database of the Dent Neurologic Institute to study the abnormal findings in myelitis. We identified 22 patients, and compared non-MS-related acute transverse myelitis (ATM, n = 9), to myelitis associated with multiple sclerosis (MS-myelitis, n = 13). The ATM patients were significantly older than MS patients at the time of the myelitis diagnosis (mean age 46 vs 35, p < 0.05). ATM appeared as a "longitudinal myelitis", with fusiform cord expansion on T ₁-weighted images and intramedullary increased signal on T ₂-weighted images, each involving multiple spinal levels (mean = 7–8). However, MS-myelitis lesions appeared focal, involving significantly fewer spinal levels (mean = 1–2, p < 0.001), although the lesions were equally likely to expand the cord. Four (42%) of the ATM lesions showed abnormal, variable enhancement, whereas none of the MS myelitis lesions enhanced. Cranial MRI was more likely to be normal in ATM (78%) than in MS-myelitis patients (15%, p < 0.001). Although readily distinguishable from lesions due to MS, the various etiologies for ATM, including post-infectious ( n = 2), post-vaccination ( n = 3), and idiopathic ( n = 4) were indistinguishable on MRI. The MRI findings of an extensively lesioned, swollen cord, suspicious for an intramedullary tumor and providing a temptation for a biopsy, may reflect a non-neoplastic inflammatory disorder.     

血清抗核抗体、可提取性核抗原、抗中性粒细胞胞质抗体对视神经脊髓炎临床特点及急性复发期脑脊液特征的影响

目的 探讨血清抗核抗体(ANA+dsDNA)、可提取性核抗原(ENA)、抗中性粒细胞胞质抗体(ANCA)对视神经脊髓炎(NMO)临床特点及急性复发期脑脊液特征的影响.方法 回顾分析1985-2009年北京协和医院收治的临床诊断为NMO的41例患者,均进行血清ANA+dsDNA、ENA和ANCA检查,比较其中14例自身抗体阳性的NMO患者与27例自身抗体阴性的患者的临床特征及急性复发期脑脊液检查结果.结果 14例(34.1%)NMO患者自身抗体阳性,与自身抗体阴性的NM0患者相比,缓解期最高的视力评分(M50,自身抗体阳性组5分,自身抗体阴性组2分)及最差视力低于眼前数指的比例(分别为42.9%和16.0%)有升高的趋势,但差异无统计学意义;自身抗体阳性组缓解期扩展神经功能缺失状况评分(EDSS,4.5)较自身抗体阴性组(2.5)明显增高(U=92.5,P=0.008),并且容易出现脊髓横断性损害(分别为3/14、0/27,x2=6.736,P=0.009),而性别、起病年龄、病程、年复发率、首发部位在2组间差异无统计学意义.2组患者急性复发期脑脊液检查结果比较,自身抗体阳性患者脑脊液白细胞数(2.0)明显升高(U=68.0,P=0.007),24 h IgG合成率有减低的趋势(分别为-8.663、0.163),但差异无统计学意义(U=30.0,P=0.053),而脑脊液蛋白、髓鞘碱性蛋白、寡克隆区带差异无统计学意义.结论合并ANA、ENA、ANCA阳性NMO患者鞘内免疫炎性反应严重,神经功能缺失较重,可能需要强化免疫治疗.     

Comparison of acute flaccid myelitis and transverse myelitis in children and evaluation of diagnostic criteria

Background and purpose

Acute flaccid myelitis (AFM) and transverse myelitis (TM) are serious conditions that may be difficult to differentiate, especially at onset of disease. In this study, we compared clinical features of pediatric AFM and TM and evaluated current diagnostic criteria, aiming to improve early and accurate diagnosis.

Methods

Two cohorts of children with enterovirus D68-associated AFM and clinically diagnosed TM were compared regarding presenting clinical features, additional investigations, and outcome. Current diagnostic criteria for AFM and TM were applied to evaluate their specificity.

Results

Children with AFM (n = 21) compared to those with TM (n = 36) were younger (median 3 vs. 10 years), more often had a prodromal illness (100% vs. 39%), predominant proximal weakness (69% vs. 17%), and hyporeflexia (100% vs. 44%), and less often had sensory deficits (0% vs. 81%), bowel and/or bladder dysfunction (12% vs. 69%), and hyperreflexia (0% vs. 44%). On magnetic resonance imaging, brainstem involvement was more common in AFM (74% vs. 21%), whereas supratentorial abnormalities were only seen in TM (0% vs. 40%). When omitting the criterion of a sensory level, 11 of 15 (73%) children with AFM fulfilled the diagnostic criteria for TM. Of children with TM, four of 33 (12%) fulfilled the diagnostic criteria for probable/definite AFM.

Conclusions

Although there is considerable overlap between AFM and TM in children, we found important early differentiating clinical and diagnostic features. Meeting diagnostic criteria for AFM in children with TM and vice versa underlines the importance of thorough clinical examination and early and accurate diagnostic studies.     

Eosinophilic Myelitis in the Cervical Cord Mimicking Intramedullary Cord Tumor

Eosinophilic myelitis (EM) or atopic myelitis is a rare disease characterized by a myelitic condition in the spinal cord combined with allergic process. This disease has specific features of elevated serum IgE level, active reaction to mite specific antigen and stepwise progression of mostly the sensory symptoms. Toxocariasis can be related with a form of EM. This report describes two cases of cervical eosinophilic myelitis initially considered as intramedullary tumors. When a differential diagnosis of the intramedullary spinal cord lesion is in doubt, evaluation for eosinophilic myelitis and toxocariasis would be beneficial.     

Clinical features of myelitis in patients with atopic symptoms]

It is rare to see atopic symptoms in patients with multiple sclerosis(MS). However, it has been reported that in atopic patients, particularly in patients with atopic dermatitis, a benign myelitis occasionally occurs. In the present report, three atopic patients with myelitis were studied clinically and neuroradiologically. All the patients were adult men(Case 1, 2, and 3 were 41-year-old, 31-year-old, and 34-year-old, respectively), and all of them had bronchial asthma without histories of atopic dermatitis. Their manifestations were not severe and were only numbness of upper and/or lower extremities. There was no motor weakness, ataxia, or urinary incontinence. MRI studies revealed a T2-high intensity lesion in the high cervical spinal cord in the two patients(Case 2 and 3) and a T2-high intensity lesion in the lumber spinal cord in the remaining patient(Case 1). Their clinical courses were essentially all benign and well responsive to steroid therapy. Although myelitis of these patients may be a first attack of MS, their findings appear to support a recently emerging concept of the atopic myelitis.     

Etiologic spectrum and functional outcome of the acute inflammatory myelitis

Clinical, neuroimaging, and laboratory features are not specific enough to establish the etiological diagnosis of the acute inflammatory myelitis (AIM). Longitudinally extensive transverse myelitis (LETM) seen on magnetic resonance imaging (MRI) has been associated with a poor functional prognosis. The aim of this study was to assess the functional outcomes of a first AIM event comparing patients with LETM vs. no LETM on MRI and to report the differential diagnosis. Clinical, radiological, biochemical aspects were collected, and Winner–Hughes Functional Disability Scale (WHFDS) was performed after 3 and 6 months. Centromedullary lesions were associated with LETM, lateral lesions with partial lesion (PL), and brain MRI lesions with multiple sclerosis and acute encephalomyelitis disseminated. LETM patients were associated with a worse functional outcome as the need of a wheelchair after 3 and 6 months (OR = 7.61 p = 0.01; OR 4.8 p = 0.04, respectively), a walker or cane (OR = 11.0 p = 0.002, OR = 4.3 p = 0.03, respectively). In addition, we found a correlation between LETM and acute complete transverse myelitis and PL with acute partial transverse myelitis (83.3 and 90.9%, respectively; p < 0.0001). In conclusion, AIM is a heterogeneous syndrome from an etiological point of view and LETM patients had worse functional prognosis compared with PL after 3 and 6 months.     

Atopic myelitis with focal amyotrophy: a possible link to Hopkins syndrome

Among 22 consecutive patients with myelitis, of unknown etiology, and atopic diathesis (atopic myelitis) who from April 2002 to March 2006 had been studied in our clinic, 5 (23%) showed focal amyotrophy in one or two limbs. These 5 patients were subjected to combined clinical, electrophysiological, neuroimaging and immunological studies. Ages were 18 to 58-years-old (average 39). Four showed amyotrophy of unilateral or bilateral upper limbs while one showed amyotrophy in both thighs. All patients showed on-going denervation potentials in the affected muscles, while motor conduction study including F wave was normal except for in one patient who showed prolonged F wave latency in one nerve. Two had localized high signal intensity lesions involving anterior horns on spinal cord MRI and three showed abnormalities suggesting pyramidal tract involvement on motor evoked potentials. All had a present and/or past history of atopic disorders and specific IgE against common environmental allergens, such as mite antigens and cedar pollens, and four showed mild eosinophilia, all of which were compatible with atopic myelitis. When clinical and laboratory findings were compared between atopic myelitis with (n = 5) or without focal amyotrophy (n = 17), the former showed a significantly higher frequency of present and past history of asthma (80% vs. 24%, p = 0.0393) and tended to have higher EDSS scores (3.8 ± 1.6 vs. 3.1 ± 1.4). Two patients showed mild to moderate improvements after immunotherapies such as methylprednisolone pulse therapy or plasma exchange, while two recovered with low dose corticosteroids and one without treatment had a gradually progressive course.

Although atopic myelitis preferentially involves the posterior column of the cervical spinal cord, it is possible that anterior horn cells are affected in some cases of atopic myelitis, especially in patients with asthma. This suggests a possible link between atopic myelitis and Hopkins syndrome (asthmatic amyotrophy).     

A case of atopic myelitis]

A 35-year old woman was admitted to our hospital because of slowly increased numbness of lower truncus and the legs for 10 months. She showed atopic dermatitis on her nape and bilateral popliteal fossa, and signs and symptoms of anorexia nervosa, such as asitia, emaciation, and menopause. Neurologic examination revealed Lhermitte's sign, muscle weakness of bilateral hands, deep and superficial sensory disturbance below the Th 4 level of thoracic spinal cord, and increased tendon reflexes of four limbs. Laboratory data showed hyperIgEemia and high titer of mite antigen specific IgE in sera. Cervical MRI demonstrated abnormal intensity area located at the C6 to C7 segments (i.e. low intensity in T1 weighted images and high in T2). She also showed hypercalcemia and swelling of the parathyroid gland, and had been diagnosed primary hyperparathyroidism by scintigram of the parathyroid gland. We concluded that this case is thought to be atopic myelitis, which has been recently reported as acute myelitis associated with hyperIgEemia and atopic dermatitis proposed by Kira et al. (1997). The patient also had anorexia nervosa and primary hyperparathyroidism.     

A case of atopic myelitis in the area other than Kyushu Island]

A case of acute myelitis associated with atopic dermatitis, hyperIgEemia and mite antigen specific IgE was reported. A 22-year old woman with a history of atopic dermatitis since her childhood began to have numbness in her legs, which extended upward to her upper part of chest in four days. Neurological examination revealed Lhermitte's sign, moderate disturbance of superficial and deep sensation below the Th4 level, and sensory ataxia. She also showed exaggerated deep tendon reflexes in the upper extremities and urinary difficulty. MRI studies revealed an intramedullary T1-low, T2-high lesions without Gd-DTPA contrast enhancement in the posterior part of the cervical spinal cord at C3 level. The laboratory examination revealed normal CSF, and the elevated level of serum IgE and mite-antigen-specific IgE in sera. We conclude that this case is thought to be atopic myelitis, which was reported as acute myelitis associated with hyperIgEemia and atopic dermatitis proposed by Kira et al. This is the first report of a case outside of Kyushu area in Japan.     

Effect of immunotherapy in myelitis with atopic diathesis

OBJECTIVE: A recent nationwide survey of myelitis with atopic diathesis in Japan disclosed that the disease frequently shows a chronic persistent course. A neuropathological study of the spinal cord also revealed chronic active inflammation. Since the effects of various immunotherapies have not been studied extensively in this condition, we evaluated the efficacies of various immunotherapies in patients with myelitis with atopic diathesis. PATIENTS AND METHODS: Forty-two treatments in 26 patients with myelitis with atopic diathesis were retrospectively analyzed. One of the following therapies was administered: (1) corticosteroids (CS) (pulse therapy followed by oral administration with gradual tapering); (2) intravenous immunoglobulin (IVIG) (400 mg/kg/day for 5 consecutive days); (3) plasma exchanges (PE); or (4) PE followed by IVIG or CS (PE+IVIG/CS). The therapeutic efficacies were evaluated by thorough neurological examination and laboratory tests including MRI, somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs). RESULTS: Objective neurological findings improved in 89% of the PE group and 90% of the PE+IVIG/CS group, compared with only 72% of the CS and 60% of the IVIG groups. Improvement determined by laboratory tests was seen in 57% of the PE and 57% of the PE+IVIG/CS groups, compared with only 15% of the CS and none of the IVIG groups. Thus, the improvement rate determined by laboratory tests was significantly greater for therapies including PE than for those without PE (p=0.0187). CONCLUSIONS: These data suggest that immunotherapy is effective in myelitis with atopic diathesis despite a chronic persistent course, and that PE is the most beneficial immunotherapy.     

Can electromyography predict the prognosis of transverse myelitis?

The role of clinical and magnetic resonance imaging (MRI) features on the prognosis of acute transverse myelitis has been studied, but the role of electromyography (EMG) changes, although reported, has not been investigated. Seventeen patients with acute transverse myelitis were subjected to clinical evaluation, MRI scanning and concentric needle EMG. The outcome was defined on the basis of a 3-month Barthel Index (BI) score as good or poor. The EMG changes in these groups were compared. All of the patients had complete paraplegia (power grade 0), except 1 who had grade III power. Mild upper limb weakness was present in 6 patients. Joint position and vibration sense were impaired in the lower limbs, and a horizontal limit to sensory loss to pinprick was present in all of the patients. Spinal MRI was abnormal in 12 of 14 patients. EMG of the lower limb muscles in the acute stage (within 15–30 days of onset) revealed fibrillations or sharp waves or both in 11 patients. At 3-month follow-up, the lower limb power had improved in 8 and upper limbs in all 6 patients. The EMG changes also improved in 6 patients; fibrillations either disappeared or were markedly reduced. The motor unit potentials (MUPs) were of long duration, polyphasic with reduced recruitment. In 5 patients, however, no MUPs could be recorded and fibrillations persisted. Lower limb hypotonia and fibrillations on EMG were significantly related to the 3-month outcome. EMG evidence of denervation in the lower limb muscles in acute transverse myelitis suggests a poor outcome as assessed by 3-month Barthel index score. Received: 16 December 1998 Received in revised form: 3 April 1998 Accepted: 5 April 1998     

Atypical transverse myelitis due to cytomegalovirus in an immunocompetent patient

Abstract Cytomegalovirus (CMV)-associated transverse myelitis is rare in immunocompetent patients. We report a 73-year-old man with no evidence of immune compromise, who developed acute transverse myelitis. Cerebrospinal fluid pleocytosis indicated central nervous system inflammation, and spinal MRI showed weak signal hypointensity in T1, hyperintensity in T2 and DP between C7 and T2, but no contrast enhancement. High CSF anti- CMV IgG index with normal CSF IgG index indicated intact blood-brain barrier, and supported the diagnosis of CMV-induced myelitis in an immunocompetent patient.     

Parainfectious myelitis: three distinct clinico-imagiological patterns with prognostic implications

Seventeen parainfectious myelitis patients were studied for site, extent and severity of lesions. Three patterns were observed each having distinct clinical, electrophysiological and MRI features: 1) focal segmentai myelitis – focal cord lesion with long tract signs and good prognosis; 2) ascending myelitis – continuous lesion from conus to mid-cord with upper and lower motor neuron signs (not necessarily spinal shock), dysautonomia and poor outcome; 3) disseminated myelitis - discrete lesions scattered throughout the cord with subtle signs in spinal segmentai distribution, above and below the transverse level and moderate outcome. Severe autonomic dysfunction, denervation of paraspinal muscles, "dense" lesion on imaging and often (but not always) the absent somatosensory evoked potentials carried poor outcome. In conclusion "parainfectious myelitis" is a better term to describe transverse myelitis, as the lesion extends to a large vertical extent. Further classification into 3 subgroups may improve understanding of anatomical and physiological dysfunction and prediction of outcome.