An early-onset case of acute disseminated encephalomyelitis with bilateral thalamic lesions on MRI]

We report the case of 5-year-old girl with acute disseminated encephalomyelitis (ADEM), whose MRI showed bilateral thalamic lesions. She suffered from left optic neuritis and generalized convulsion. Examination of cerebrospinal fluid revealed elevation of mononuclear cells and myelin basic protein (MBP). MRI showed the swelling of left optic nerve and high intensity areas of bilateral thalamus. After methylprednisolone pulse therapy, her visual acuity was dramatically improved and bilateral thalamic lesions were decreased. In childhood, bilateral thalamic lesions were observed in several diseases, such as viral encephalitis. Reye syndrome, Leigh syndrome and acute necrotizing encephalopathy. Demyelinating diseases involving the grey matter were very rare, but we must consider the presence of symmetrical thalamic involvement in patients with ADEM.     

A case of acute disseminated encephalomyelitis after renal transplantation]

We report a patient of acute disseminated encephalomyelitis (ADEM) in a recipient of renal transplantation. A 43-year-old man suffered from generalized convulsion and consciousness disturbance followed by coma on day 53 of after the transplantation. He was receiving several immunosuppressants, and an increase of serum antigen for cytomegalovirus was observed one day before the ictus. T2 and diffusion-weighted image of MRI showed high intensity lesions in the bilateral cerebral white matter, basal ganglia, thalamus, midbrain, pons and cerebellum. Examination of cerebrospinal fluid revealed elevated myelin basic protein level. The patient was diagnosed as having ADEM and was treated with methylpredonisolone pulse therapy in combination with intravenous immune globulin. He gradually recovered and became capable to eat and sit on a wheel chair. White matter lesions on MRI were also diminished. ADEM may occur in recipients of organ transplantation even if they have immunosuppressive treatment.     

Acute disseminated encephalomyelitis in a 3-month-old infant

Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease showing multifocal central nervous system lesions due to an autoimmune disorder. We reported a 3-month-old girl with ADEM. One week after having a cold, she presented with somnolence, poor feeding and vomiting. When she was admitted three days after the onset, she could neither fix or follow objects with her eyes nor respond to sound. Her muscle tone was decreased. Cerebrospinal fluid examination revealed pleocytosis, elevated protein concentration and positive myelin basic protein. No oligoclonal band was detected. Diffuse monomorphic slow wave activity was noted on the electroencephalogram. Only wave I was present bilaterally on the auditory brainstem response. T2 weighted images of magnetic resonance imaging revealed multiple areas of high signal in the right posterior limb of the internal capsule, white matter of the cerebellum and brainstem. She was diagnosed as having ADEM, and underwent high dose gamma-globulin therapy. Corticosteroids were not given because of her high blood pressure. The clinical symptoms improved continuously before and after the administration. Two years after the onset, she showed normal growth and development without reoccurrence. The age at onset of childhood ADEM is usually 3 or 4 years. ADEM before one year of age is very rare. The demyelinating lesions of this case corresponded to the regions which normally become myelinated by 3 months. Although ADEM is usually treated with corticosteroids, high dose gamma 1-globulin therapy can be considered if patients are very young or have a high risk for corticosteroid, or respond poorly to corticosteroids.     

Expression of myelin basic protein mRNA and polypeptides in mouse oligodendrocytes in culture: differential regulation by genetic and epigenetic factors

We have analyzed the effects of genetic and epigenetic factors on the steady-state levels of myelin basic protein mRNA and polypeptides during development of mouse oligodendrocytes in culture. Oligodendrocytes were characterized by immunofluorescent staining with antibodies for the following markers: galactocerebroside, myelin basic protein, proteolipid protein, myelin-associated glycoprotein and 2',3'-cyclic nucleotide phosphohydrolase. Oligodendrocytes expressing one or more of these markers first appeared at 3 days in culture and increased to a maximum of 1.5 X 10(5) per brain around 6 days, after which the number remained constant up to 31 days. In medium containing fetal calf serum, accumulation of myelin basic protein polypeptides was delayed relative to in vivo in cultures derived from C57BL/6J, BALB/cJ and DBA/2J inbred mice, but not in cultures derived from C3H/HeJ and AKR/J inbred mice. In medium containing serum from other species or in serum substitute, the temporal expression of myelin basic protein polypeptides in cultures from all the inbred strains was contemporaneous with that in brain. Northern hybridization analysis indicated that the steady-state level of myelin basic protein-specific mRNA in all cultures was regulated similarly to in vivo suggesting that the delayed expression of myelin basic protein polypeptides in some cultures was due to translational and/or post-translational regulation. Analysis of myelin basic protein expression in cultures from informative hybrid and recombinant inbred strains indicated that translational or post-translational expression of myelin basic protein requires trans-acting factors, the inducibility of which is controlled by multiple genetic determinants which segregate independently and are expressed additively.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of ADEM with atypical MRI findings of a centrally-located long spinal cord lesion

The patient was a 14-year-old male diagnosed with acute disseminated encephalomyelitis (ADEM) with acute onset of multifocal central nervous system symptoms. He showed increased cerebrospinal fluid cell counts and high myelin basic protein levels, which responded well to steroid pulse therapy. Spinal MRI showed a centrally-located long spinal cord lesion (LCL) involving 17 vertebral bodies from C2 to T11 that later expanded into the white matter, and lesions on the ventral side of the medulla. The cause of LCL has been reported to be heterogeneous. In this case, LCL is considered to be associated with ADEM, an acute autoimmune response to myelin, and vascular inflammation of the gray matter of the spinal cord.     

Callosal disconnection syndrome due to acute disseminated enchephalomyelitis]

We have reported a very rare case of a patient with callosal disconnection syndrome due to acute disseminated enchephalomyelitis (ADEM). A 54-year-old right-handed woman developed sudden consciousness disturbance and fever after 2 weeks when she had common cold. She did not have a history of stuttering. On admission, the neurological finding showed consciousness disturbance, and exaggerated muscle stretch reflex in four extremities without meningeal irritation. The cerebrospinal fluid examination revealed the cell counts of 273/mm3, the protein of 348 mg/dl and the myelin basic protein 18.3 pg/ml. The brain MRI demonstrated a focal high signal intensity in the right cerebellar peduncle, right temporal lobe, left occipital lobe and corpus callosum on the T2-weighted and FLAIR images. The lesion of corpus callosum was the trunk and splenium, sparing the dorsal side of splenium. Her diagnosis was ADEM. The steroid pulse therapy (metylpredinisolone 1 g/day for 3 days) improved the consciousness disturbance. After 6 weeks from the onset, the neuropsycological examination was performed. The remarkable findings included pure alexia without color naming defects, the acquired stuttering and one-way disturbance of somesthetic transfer from the left hand to the right. This patient may contribute to the study of functional localization of the corpus callosum.     

Serial changes of magnetic resonance imagings in acute disseminated encephalomyelitis]

We reported serial changes of MRIs in a case of acute disseminated encephalomyelitis (ADEM). On November 1, 1990, a previously healthy 73-year-old man had a grand mal seizure following myoclonic jerks of the right arm for six days. On admission, he was drowsy and presented with right facial palsy and incomplete tetraparesis. He became coma on the next day of admission. There was moderate leukocytosis. A spinal tap showed a normal opening pressure, 2 white blood cells/mm3, a total protein of 84 mg/dl, glucose of 89 mg/dl. CSF IgG (6.2 mg/dl) and myelin basic protein (6.7 ng/dl) were slightly increased. Serological examinations for virus titer were all negative. A CT scan on the 2nd day showed no abnormal findings, but MRI revealed small high intensity areas in the left thalamus, left prefrontal gyrus and right corona radiata, internal capsule on both the T2-weighted and proton density sequences. An MRI on the 14th day showed high intensity signals in the white matter of the bilateral frontal lobes, left operculum and right corona radiata. In contrast, the left thalamic lesion became smaller and less conspicuous than on the initial scans, but was enhanced with Gd on the T1-weighted sequences. Our findings indicate that MRIs are valuable in detecting pathophysiological changes of ADEM from the acute to chronic phases.     

Autoantibodies in childhood post-varicella acute cerebellar ataxia

BACKGROUND: Anti-Purkinje cell antibodies have been reported in cerebellar ataxia following Epstein-Barr virus (EBV) infection. We investigated autoantibody responses, including anti-Purkinje cell antibodies, and the clinical course in eight children who developed post-varicella ataxia, five of their siblings with uncomplicated varicella, one child with post-EBV ataxia, two children with acute disseminated encephalomyelitis (ADEM) and one with neuroblastoma associated ataxia, and in age and gender matched controls. METHODS: Autoantibodies were tested by indirect immunofluorescence (IIF) on cryopreserved cerebrum and cerebellum sections. Other autoantibodies were measured by conventional IIF protocols using HEp-2 cells as a substrate. Antibodies to myelin associated glycoprotein (MAG), asialo-GM1, beta2 glycoprotein 1, cardiolipin and myelin basic protein (MBP) were measured by ELISA. RESULTS: Three of eight children with acute post-varicella ataxia, one child with post-EBV ataxia, one child with ADEM and one child with uncomplicated varicella, had high titer autoantibodies (>1/160) that reacted with cerebrum and cerebellar tissue. This reactivity was not seen in one child with ADEM, in one with neuroblastoma and ataxia, in the remainder of the children with uncomplicated varicella or age and gender matched controls. Autoantibodies were not seen in CSF from two children with post-varicella ataxia. The punctate staining seen on cerebrum and cerebellum sections co-localized with rabbit antibodies to the centrosome protein pericentrin. All patients with strong reactivity with cerebrum and cerebellar tissue by IIF had elevated levels of anti-MAG that was not confirmed by absorption assay. No reactivity was seen with asialo-GM1, MBP, beta2 glycoprotein 1 or cardiolipin. None of the sera had autoantibodies directed against endosomes, the Golgi complex, or the paraneoplastic autoantigens Hu and Yo. CONCLUSION: Some children with post-viral ataxia develop antibodies that have strong reactivity with cerebral and cerebellar tissue. Some of the antigenic reactivity co-localized with the centrosome protein pericentrin.     

Fetal alcohol delays the developmental expression of myelin basic protein and transferrin in rat primary oligodendrocyte cultures.

This study has examined the development of immunoreactive myelin basic protein and transferrin in primary glial cell cultures. Cultures were initiated from control and experimental Sprague-Dawley rats 1-2 days postnatally. Experimental treatment involved exposure to 5% (w/v) ethanol in a liquid diet during the last two weeks of gestation. Prenatal alcohol administration delayed the expression of myelin basic protein and transferrin during the first three weeks postnatally. Other oligodendroglial and astroglial markers were little affected, if at all, by fetal alcohol exposure.     

COST-BENEFIT RATIO OF INTRAVENOUS IMMUNOGLOBULIN TREATMENT IN CHRONIC INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY

Intravenous immunoglobulin (IVIG) is considered an efficacious but expensive treatment in dysimmune polyneuropathies. Nevertheless, to date, no studies have been conducted on the cost of this therapy. We retrospectively studied 21 patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (idiopathic-CIDP and CIDP-MGUS), comparing the clinical response and costs of IVIG therapy with those of plasma exchange (PE). Patients were treated either with IVIG (400 mg/Kg/die for five days) or PE (6 exchanges in 3 weeks). Responders continued the same therapy, which was progressively tapered down to one IVIG infusion or one PE monthly. IVIG nonresponders received PE and vice versa. Patients were followed for a period ranging from 3 to 67 months (median: 29 months). The modified Rankin disability scale was used to determine functional impairment at baseline and during treatment.
Eleven of 21 patients (52%) improved with the first choice of treatment. Of the remaining 10 patients, 3 benefited from the alternative treatment; 2 patients who did not respond to the alternative treatment were again treated with the first choice therapy and subsequently improved; 2 patients on IVIG abandoned the therapy. One nonresponder to IVIG is currently receiving PE. The overall response rate to the two therapies was similar. The mean cost per patient was 1,128,000 lire/session for PE therapy (excluding equipment and medical staff costs) and 1,204,000 lire/dose for IVIG therapy. However, the responders to PE required a longer treatment than responders to IVIG.     

Encephalomyelitis-associated antimyelin autoreactivity induced by streptococcal exotoxins

OBJECTIVE: After implicating Streptococcus pyogenes as causing acute disseminated encephalomyelitis (ADEM) in a child, we wanted to prove that in vivo activation of autoreactive T lymphocytes by superantigens of this Streptococcus contributed to the dramatic demyelination. BACKGROUND: ADEM is a demyelinating disorder of the CNS sharing many similarities with MS. Demyelination in MS is considered to be the result of an autoimmune process mediated by autoreactive T lymphocytes with specificity for myelin antigens. METHODS: Phenotypic analysis and proliferation assays on blood monocytes, as well as isolation of myelin basic protein (MBP)-reactive T-cell lines/clones; and TCR repertorium analysis by PCR-ELISA and cytokine production. RESULTS: 1) The blood T-cell receptor (TCR) repertoire was compatible with in vivo expansion induced by S. pyogenes exotoxins. 2) TCR expression analysis indicated clonal expansion of CD8+ MBP-reactive T cells, suggesting in vivo activation. MBP-reactive T cells showed crossreactivity to S. pyogenes supernatant and exotoxins. 3) Cytokine mRNA quantification of the mononuclear cells revealed a Th2-biased profile. CONCLUSION: In vivo exposure to S. pyogenes may have induced activation of pathogenic myelin reactive T cells, contributing to the dramatic inflammatory demyelination.     

Tau protein concentrations in the cerebrospinal fluid of children with acute disseminated encephalomyelitis

Background: Acute disseminated encephalomyelitis (ADEM) is clinically characterized by the acute onset of neurological symptoms after a viral infection or immunization, and is thought to represent an autoimmune disease directed against myelin. Tau protein is a phosphorylated microtubule-associated protein, primarily located in neuronal axons. Increased levels of tau protein in cerebrospinal fluid (CSF) are found in various pathological conditions. Methods: We used tau protein as a marker of axonal damage and examined its concentration in the CSF of 27 children with ADEM. Results: CSF tau protein concentration in children with ADEM was significantly higher than that in the CSF of control subjects (P = 0.008). There were no significant differences in CSF tau protein concentrations in the ADEM patients with and without encephalopathy. The CSF tau protein concentration in patients with partial lesion resolution in follow-up brain MRI was significantly higher than in patients with complete lesion resolution (P = 0.014). Conclusions: In conclusion, we demonstrated that CSF tau protein concentration was significantly increased in ADEM patients. Our findings suggest that axonal damage may occur in addition to demyelination in children with ADEM.     

The head MRI by fluid attenuated inversion recovery (FLAIR) was useful for diagnosis in the patient with post influenza vaccinal acute disseminated encephalomyelitis (ADEM)

A 6-year-old, previously healthy boy developed ataxia and muscle weakness, 16 days after influenza vaccination. The CSF showed an elevated level of myelin basic protein, pleocytosis and negative influenza virus isolation. The head MRI revealed an extensive high intensity area in the deep white matter, which was more clearly defined on FLAIR images. The diagnosis of post influenza vaccinal ADEM was made, and he was successfully treated by steroid pulse therapy with a monophasic course and favorable outcome.     

Intravenous immunoglobulin monotherapy in long-term treatment of myasthenia gravis

OBJECTIVE: To investigate effectiveness of long-term treatment of myasthenia gravis (MG) with intravenous immunoglobulin (IVIG). BACKGROUND: There are no definitive studies showing effectiveness of IVIG therapy in long-term treatment of MG. Most studies have investigated the acute treatment of MG with IVIG. We describe our experience with long-term treatment of MG with IVIG in six patients. METHODS: Acute treatment of MG by IVIG therapy has been well established in the literature. We describe six patients who were treated on a long-term basis with IVIG therapy. All of these patients had positive acetylcholine receptor antibody titers. They all received initial infusion for 5 days of IVIG at a dose of 400 mg/kg/day followed by maintenance therapy of 400 mg/kg for 1 day every 3-4 months. These patients were followed for 2 years. All other medications, including prednisone and cholingeric drugs such as Mestinon, were gradually weaned. For the last years, each of these patients maintained better than functional class 2 on an average of 1.5-2.2+/-0.5 grades on the University of Virginia modification of Ossermann's classification scale for MG. They were solely treated with IVIG infusion every 3-4 months without any other concomitant medications. Three of the patients had previously undergone thymectomies. None of the patients noticed any worsening in their scores on the University of Virginia modification of Ossermann's classification worse than Grade II in the last 2 years. There were no complications related to IVIG therapy, and all patients tolerated a single infusion of IVIG every 3-4 months at 400 mg/kg for 1 day. RESULTS: Our study demonstrates that IVIG maintenance is effective treatment of MG in selected patients and it is well tolerated. CONCLUSIONS: IVIG therapy is a convenient, effective therapy when used selectively for treatment of MG on a long-term basis without any significant side effects.     

Acute disseminated encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is an uncommon inflammatory demyelinating disease of the central nervous system. The true incidence of the disease in India is undetermined and is likely to be more frequent than reported, as the common antecedent events, exanthematous fevers and Semple antirabies vaccination, which predispose to ADEM, are still prevalent. The existing evidence suggests that ADEM results from a transient autoimmune response towards myelin or other self-antigens, possibly via molecular mimicry, or by non-specific activation of auto-reactive T cell clones. ADEM is a monophasic illness with favourable long-term outcome. Involvement of neuroaxis is variable and can be diffuse or multifocal and site restricted. Magnetic resonance imaging (MRI) is highly sensitive in detecting white matter lesions and the lesions described are rather extensive and subcortical in location. Involvement of the deep gray matter, particularly basal ganglia, is more frequent. Oligoclonal bands in CSF are usually absent. No therapy has been established by controlled trials in ADEM. Use of high-dose methylprednisolone, plasma exchange, and IVIG are based on the analogy of the pathogenesis of ADEM with that of multiple sclerosis (MS). Differentiation of ADEM from the first attack of MS is important from prognostic as well as therapeutic point of view. However, in the absence of biological marker, at times differentiation of ADEM from the initial presentation of MS may not be possible even by combination of clinical, CSF analysis, and MRI. This differentiation is more relevant to India where the incidence of MS is low.     

Acute disseminated encephalomyelitis after bee sting

Acute disseminated encephalomyelitis (ADEM) usually follows a viral infection or an immunization and is thought to be an immunomediated disease. We describe a patient with ADEM after multiple yellow jacket bee stings. The patient recovered after treatment with a high dose of methylprednisolone. Although the pathologic mechanism exact remains unclear, potential cross-reactivity between bee toxins and the central nervous system myelin could induce demyelination. ADEM should be considered a rare complication of bee stings. Received: 15 April 2002 / Accepted in revised form: 5 December 2002 Correspondence to C. Boz     

Single dose immunoglobulin therapy for childhood Guillain-Barrésyndrome

To establish the efficacy of intravenous immunoglobulins (IVIG) in the treatment of acute Guillain-Barrésyndrome (GBS), we treated nine consecutive pediatric cases (age 2.5–13.5 years) fulfilling the criteria for GBS with a single dose of IVIG (Sandoglobulin; 2 g/kg/BW). None of the patients experienced any IVIG related side-effects. The mean time required to improve by at least one grade on the functional GBS scale after IVIG treatment was 3.5 days, while the mean period to regain ambulation was 11.2 days. Full mobilization without evidence of relapse in the follow-up period (mean 14.5 months) was noted in all but one patient who relapsed after 5 months. We conclude that the early use of a single IVIG dose may prevent further progression of the disease, thus shortening the clinical course of childhood GBS. The mose beneficial IVIG dose regimen remains to be determined by controlled trials.     

Neutropenia as a complication of high-dose intravenous immunoglobulin therapy in adult patients with neuroimmunologic disorders

To investigate clinical aspects of the neutropenia induced by high-dose intravenous immunoglobulin therapy (IVIG) we performed serial hematology, including differentiation of white blood cells (WBC), before and after 22 instances of IVIG in 16 patients with neuroimmunologic disorders. WBC and neutrophils showed a significant decrease with a nadir 2 days after IVIG, but returned to previous values by 14 days with no treatment except in 2 cases. No patient showed any infectious complication. Both WBC and neutrophils were significantly decreased in cases without corticosteroid therapy but not in those with medication. In nine instances (4 with and 5 without corticosteroid treatment), CD11b and CD16 on neutrophils were investigated using flow cytometry. In 3 of 5 instances without corticosteroid treatment the expression of CD11b was decreased after IVIG, while no change was detected in CD16. There was no difference in either CD11b or CD16 between before and after IVIG in instances with corticosteroid therapy. Neutropenia commonly and transiently develops just after IVIG, and can be prevented by corticosteroid pretreatment. Circulating neutrophils might bind to the vascular wall mainly with the involvement of CD11b and migrate into a storage pool, resulting in an apparent neutropenia after IVIG.     

Clinical time course of pediatric acute disseminated encephalomyelitis

The detailed clinical time course in acute disseminated encephalomyelitis (ADEM) from initial symptoms, through exacerbation, to remission has not been widely reported. Hence, this study aimed to investigate the clinical time course of pediatric ADEM. This was a multicenter retrospective study based on registry data from medical chart reviews. The study included children who met the international consensus diagnostic criteria for ADEM. The patients comprised 18 boys and 6 girls, with a mean age of 5.5?±?3.3?years at onset. From onset, the time until peak neurological symptoms, time until initial improvement, and time until full recovery was 3.1?±?3.7?days, 6.0?±?4.5?days, and 26?±?34?days, respectively. Twenty-three (96%) patients were treated with high-dose methylprednisolone (mPSL) with a mean duration of 4.1?±?4.0?days from onset. The condition of 15 patients (65%) improved within 3?days of high-dose mPSL initiation, whereas, that of four patients began to improve after >5?days of high-dose mPSL initiation. Only one patient (4%) did not achieve full recovery despite treatment with high-dose mPSL, intravenous immunoglobulin, and plasma exchange. This study presents the detailed clinical time course in pediatric ADEM in Japan. Progression of neurologic deficits typically lasts a few days, with initial improvement in 1?week leading to full recovery within 1?month.     

The differentiation of synthesis from incorporation of basic protein in quaking mutant mouse myelin

The incorporation of radioactive label into the myelin basic protein isolated from whole brain and from purified myelin of Quaking mice and normal littermates was compared. Four Quaking mice (32 days) and 4 littermate controls were injected intracranially with 150 μCi [2-²H]glycine and 25 μCi of [2-¹⁴C]glycine, respectively. One hour later, the 8 mice were sacrificed and their brains combined for common homogenization. The ³H/¹⁴C ratios of the small and large basic proteins in whole brain were 3.44 and 2.48 respectively, while the ³H/¹⁴C ratios for these proteins in myelin were 0.79 and 1.00, respectively. In the same experiment, the microsomal fraction had a ³H/¹⁴C ratio of 2.98 which is the expected ratio for normal incorporation. The results indicate that the synthesis of basic protein in whole brain of Quaking mouse proceeds at a normal rate, but specifically, the incorporation of basic protein into myelin is depressed suggesting a defect at the step of assembly of myelin components into a final membrane product.