Course Of Intravenous Immunoglobulin Therapy Research Articles

Idiopathic autoimmune encephalitis with a recurrent course. A case report

We presented a clinical case of idiopathic autoimmune brainstem encephalitis in a 12-year-old female patient. At the onset of the disease, which developed after a respiratory infection, the clinical picture was accompanied by oculomotor and bulbar syndromes. The diagnosis of Bickerstaff brainstem encephalitis was made based on clinical diagnostic criteria and the positive effect of the course of intravenous immunoglobulin therapy. During 3 years of follow-up, there were periods of relapse of the disease, during which symptoms not typical for Bickerstaff stem encephalitis appeared. Against the background of long-term immunosuppressive therapy, there was a long-term remission of about 2 years. The clinical picture, the presence of relapses, the data of additional methods forced to reconsider the diagnosis in favor of idiopathic autoimmune brainstem encephalitis.

28645 IgG lambda monoclonal gammopathy, scleromyxedema, and sensorimotor neuropathy

A 74-year-old gentleman presented with 8-week history of a spreading rash which affected the dorsal hands, eyebrows, chin, nasal bridge, retroauricular, and posterior neck. It was accompanied with a sensation of tightness and paraesthesia to the hands. His background medical problems included hypertension and benign prostatic hypertrophy and his medications had remained unchanged for a number of months. His blood tests were entirely normal except for a raised monoclonal IgG lambda. A skin biopsy was performed which revealed the histologic triad of mucin deposition in the upper-to-mid-dermis, increased collagen deposition and marked, irregularly arranged fibroblast proliferation in keeping with a diagnosis of scleromyxoedema. The patient was started on oral PUVA therapy due to the difficulty in obtaining funding for intravenous immunoglobulin (IVIg) therapy and this had little effect. Around 18 months later, he was admitted to the hospital with a four week history of dysarthria, dysphagia, limb weakness, and type 1 respiratory failure. Nerve conduction studies showed an axonal sensorimotor neuropathy which was confirmed on nerve biopsy. An MRI scan of the brain showed only small vessel ischamic changes with nil acute pathology. He responded well to an acute course of intravenous immunoglobulin therapy but still displayed residual neurologic symptoms. We present an unusual case of IgG lambda monoclonal gammopathy, scleromyxedema, and sensorimotor neuropathy who responded to IVIg therapy.

ACUTE CORONARY SYNDROME FOLLOWING INTRAVENOUS IMMUNOGLOBULIN THERAPY : A HIDDEN RISK

Intravenous immunoglobulin (IVIG) is one of the main line modalities of therapy for chronic inammatory demyelinating polyneuropathy (CIDP). We hereby, report an incidence of acute myocardial infarction probably induced by IVIG during the treatment of CIDP. A 76 year old female with no history suggestive of cardiovascular disease, developed an acute Non ST Segment Elevation Myocardial Infarction (NSTEMI) and severe left ventricular dysfunction after receiving three doses of IVIG. Since hypercoagulability is a concern with IVIG therapy, it was discontinued. Hence, we highlight the importance of cardiac evaluation before initiation and during the course of IVIG therapy in elderly patients as well as in patients with known risk factors for cardiovascular disease and thrombotic events.

A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease

BackgroundKawasaki disease (KD) is a systemic vasculitis which may be associated with coronary artery aneurysms. A notable risk factor for the development of coronary artery aneurysms is resistance to intravenous immunoglobulin (IVIG) therapy, which comprises standard treatment for the acute phase of KD. The cause of IVIG resistance in KD is largely unknown; however, the contribution of genetic factors, especially variants in immune-related genes, has been suspected.MethodsTo explore genetic variants related to IVIG-unresponsiveness, we designated KD patients who did not respond to both first and second courses of IVIG therapy as IVIG-unresponsive patients. Using genomic DNA from 30 IVIG-unresponsive KD patients, we performed pooled genome sequencing targeting 39 immune-related cytokine receptor genes.ResultsThe single nucleotide variant (SNV), rs563535954 (located in the IL4R locus), was concentrated in IVIG-unresponsive KD patients. Individual genotyping showed that the minor allele of rs563535954 was present in 4/33 patients with IVIG-unresponsive KD, compared with 20/1063 individuals in the Japanese genome variation database (odds ratio = 7.19, 95% confidence interval 2.43–21.47). Furthermore, the minor allele of rs563535954 was absent in 42 KD patients who responded to IVIG treatment (P = 0.0337), indicating that a low-frequency variant, rs563535954, is associated with IVIG-unresponsiveness in KD patients. Although rs563535954 is located in the 3′-untranslated region of IL4R, there was no alternation in IL4R expression associated with the mior allele of rs563535954. However, IVIG-unresponsive patients that exhibited the minor allele of rs563535954 tended to be classified into the low-risk group (based on previously reported risk scores) for prediction of IVIG-resistance. Therefore, IVIG-unresponsiveness associated with the minor allele of rs563535954 might differ from IVIG-unresponsiveness associated with previous risk factors used to evaluate IVIG-unresponsiveness in KD.ConclusionThese findings suggest that the SNV rs563535954 could serve as a predictive indicator of IVIG-unresponsiveness, thereby improving the sensitivity of risk scoring systems, and may aid in prevention of coronary artery lesions in KD patients.

Clinical features of 19 children with Bickerstaff brainstem encephalitis

Objective: To summarize the clinical features of Bickerstaff brainstem encephalitis (BBE) in children. Methods: In this retrospective study, data of 19 patients with BBE (11 males and 8 females) were collected from Department of Neurology, Beijing Children's Hospital from October 2015 to January 2018. The clinical features, treatment and prognosis were analyzed. Results: The onset age of BBE ranged from 1 year and 8 months to 12 years and 11 months. There were 18 cases with preceding infection. The most common infection was upper respiratory tract infection (9 cases), followed by simple fever (5 cases). The most common initial neurological symptoms were lethargy or disturbance of consciousness (8 cases), followed by limb weakness (5 cases). There were 6 cases of simple BBE and 13 cases of BBE overlapping Guillain-Barré syndrome (GBS). Besides the characteristic triad of altered mental status, ataxia, and ophthalmoplegia, there were other symptoms including convulsion (5 cases), diplopia (3 cases), nystagmus (7 cases), facial muscular weakness (7 cases),bulbar palsy (13 cases) and autonomic nerve symptoms (9 cases). Hypo or areflexia was seen in 16 cases. Positive Babinski's signs were seen in 8 cases. Hyponatremia was present in 10 cases in whom 4 showed severe hyponatremia. Albumin-cytological dissociation of cerebrospinal fluid was seen in 10 cases. The autoimmune antibodies were examined in all 19 patients. Anti-ganglioside antibodies including anti-GM1 IgG antibody was positive in 2 patients and one of whom was also found with positive anti-GD1b IgG antibody. Anti-GQ1b IgG antibody was present in 2 patients. Electromyography was performed in 14 cases and 8 cases, who were all BBE overlapping GBS, showed neurological damage. A total of 16 cases were monitored by video electroencephalography and 8 cases showed slow waves of background. In addition to, interictal focal discharge was detected in 2 cases. T2 fluid-attenuated inversion recovery (FLAIR) sequence abnormal signals were detected in 3 of 18 cases performed brain magnetic resonance imaging (MRI), and lesions involved with brainstem, basal ganglia, thalamus, cerebellum, corpus callosum and cerebral cortex. Lesions involved cervical and thoracic spinal cord were found in 1 out of 11 cases for whom spinal cord MRI was performed. All of the 4 cases who underwent enhanced MRI of spinal had partial nerve roots enhancement. All of the 19 patients received 1 to 2 courses of intravenous immunoglobulin therapy, and 2 cases also received plasma exchange. Fifteen cases received steroid therapy. The following-up period ranged from 3 months to 2.5 years. Two cases were lost to follow-up. Twelve cases achieved a full recovery within 3 months. Three cases recovered within 6 months. One case still had slight limb weakness and ataxia after 1 year and 8 months of follow-up, and another case had left autonomic nerve symptoms in the follow-up of 2 years and 3 months. Both of them were BBE overlapping GBS. Conclusions: Children's BBE is similar to that in adults, and is frequently found overlapped with GBS. Furthermore, it is sometimes accompanied by central nervous system demyelination disease. The antiganglioside antibodies are not often detectable. Immunoglobulin therapy could usually achieve good response. The prognosis of simple BBE is good in most situations. For BBE overlapping GBS, the more severe the limb weakness during the peak of disease is, the slower the recovery would be.

Treatment and Rehabilitation of Motor Neuron Syndrome Associated with Sjögren's Syndrome: A Case Report

We report a patient with motor neuron syndrome accompanying Sjögren’s syndrome. The patient showed progressive quadriparesis and slurred speech, but neither sensory involvement nor detrusor dysfunction was noted. EMG displayed upper and lower motor neuron damage. Although sicca symptom was not too obvious, parotid gland and submandibular gland ultrasound showed diffuse lesions. The Laboratory tests also displayed markedly elevated levels of Anti-SSA and anti-Ro 52 antibody. After a course of intravenous immunoglobulin therapy and 3 weeks of comprehensive rehabilitation, the patient showed significant improvements in terms of speech, muscle strength, trunk balance, posture control and ability of daily life. We suggested that the possibility of autoimmune-mediated motor neuron damage should be considered, when patients with motor neuron syndrome accompanying Sjögren’s syndrome. And they may benefit from intravenous immunoglobulin therapy and appropriate rehabilitation.

Bickerstaff brainstem encephalitis, acute transverse myelitis, and acute motor axonal neuropathy: diagnostic and treatment challenges in patients with concomitant syndromes. Clinical observation

We report a 40-year-old woman presented with consciousness disturbance, ataxia, asymmetrical limb weakness, hyperreflexia. Due to magnetic resonance imaging findings, the patient was diagnosed with Bickerstaff’s brainstem encephalitis overlapped with acute transverse myelitis. Later she developed distal muscles atrophy and the electroneuromyographic study revealed axonal motor neuropathy, therefore acute motor axonal neuropathy was diagnosed. The patient underwent one course of intravenous immunoglobulin therapy with the regression of symptoms and magnetic resonance imaging changes. Nine months after symptoms onset, the patient has completely recovered. This overlapping case of Bickerstaff’s brainstem encephalitis, acute transverse myelitis and acute motor axonal neuropathy provides further support that these conditions are part of the same spectrum.

A severe anti-NMDA-receptor encephalitis case with extensive cortical and white matter changes, cerebral atrophy and communicating hydrocephalus

A 21-year-old woman presented with a viral prodrome, abnormal behaviours, confusion and short-term memory loss, followed by status epilepticus that later evolved to orofacial dyskinesias, autonomic dysfunctions and hypoventilation requiring prolonged ventilator support and ICU admission. Cerebrospinal fluid (CSF) and serum analysis confirmed the presence of anti-NMDAR autoantibodies. A left salpingoopherectomy was performed on day 35 of admission revealing an immature ovarian teratoma. Following surgical and two courses of intravenous immunoglobulin therapy, her response remained poor. Initial brain magnetic resonance imaging (MRI) during the acute stage showed enlarged left hippocampus. Further MRI follow-up 13 weeks after admission showed unusual findings of extensive cortical and white matter changes, generalised cerebral atrophy, dilated ventricles and possible transependymal CSF seepage of communicating hydrocephalus. A ventriculo-peritoneal shunt was performed subsequently and she was discharged 6 months after admission without significant change in her clinical status. Follow-up 4 months later showed some improvement but patient remained severely disabled.

Novel FDG-PET Findings in Anti-NMDA Receptor Encephalitis

The clinical manifestation and nuclear imaging findings in a 15-year-old boy with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis are described in this case report. The previously healthy patient presented with new onset hallucinations, seizure, and within a week, his mental status rapidly deteriorated to nonverbal with oro-lingual-facial dyskinesias. An extensive laboratory work-up for encephalopathy was negative. Repeated brain magnetic resonance imaging (MRI) studies were normal. On day 26 of admission, nuclear imaging using fluorodeoxyglucose positron emission tomography (FDG-PET) showed global hypometobolism with a prominent focally intense hypermetabolic lesion in the right cerebellar cortex. Diagnosis of anti-NMDAR encephalitis was confirmed with quantitative serology. The patient showed clinical signs of improvement after 2 courses of intravenous immunoglobulin therapy over 4 weeks. On day 46, repeat brain FDG-PET showed overall improvement but in contrast to the previous, the right cerebellar cortex showed focal hypometabolism. This is the first reported case of such findings using FDG-PET in anti-NMDAR encephalitis.

An Unusual Cause of Fulminant Guillain-Barré Syndrome: Angel's Trumpet

A 5-year-old previously healthy boy presented with typical findings of Guillain-Barré syndrome and unilateral tonic pupil. He was placed on mechanical ventilation for 35 days for respiratory failure. Plasmapheresis and two courses of intravenous immunoglobulin therapy were given to the patient, and he experienced stepwise recovery from his illness. This case of acute motor axonal neuropathy type Guillain-Barré syndrome is novel in that the cause was established as ingestion of a toxic solanaceous plant, angel's trumpet (Brugmansia suaveolens; syn. Datura suaveolens). Understanding the signs and symptoms of angel's trumpet toxicity can allow for early diagnosis and proper case management.

Guillain-Barré Syndrome Variant: Presenting with Myalgias and Acute Facial Diplegia

A patient with no significant medical history presented with myalgias, lower extremity weakness, and facial diplegia. Upon review of systems, the patient denied any other problems. Physical examination results were remarkable for weakness in the right leg and bilateral facial diplegia. Radiological and laboratory studies were unremarkable. Lumbar puncture revealed albuminocytological dissociation. The combined history, physical examination, and lumbar puncture results established a presumptive diagnosis of Guillain-Barré syndrome. The patient began a 5-day course of intravenous immunoglobulin therapy. At the end of the 5-day course, the patient had recovered 85% of her facial muscle function and experienced complete relief of her myalgias. Upon discharge, the patient was referred to physical therapy for improvement of her facial muscle impairment.

Upper Motor Neuron Syndrome Associated with Subclinical Sjoegren's Syndrome

We present two patients with primary lateral sclerosis-like upper motor neuron disease accompanying subclinical Sjögren's syndrome. Both patients showed progressive spastic quadriparesis, but neither sensory involvement nor detrusor dysfunction was noted. Lower motor neuron signs were detected only in their late follow-up period. Although sicca symptom was nearly absent, salivary labial gland biopsy revealed marked sialoadenitis in both patients. They also displayed a constellation of findings that suggested an autoimmune etiology closely related to Sjögren's syndrome, including germinal center formation in one patient, and markedly elevated levels of anti-nuclear antibody with abnormal sialography in the other. Both patients showed significant neurological improvement after the initial course of intravenous immunoglobulin therapy. We suggest that the evidence for subclinical Sjögren's syndrome should be sought in patients presenting with selective upper motor neuron involvement.

Acute Renal Failure, Translocational Hyponatremia and Hyperkalemia following Intravenous Immunoglobulin Therapy

Background/Aims: Intravenous immunoglobulin (IVIG) therapy has been associated with renal adverse effects and electrolyte disturbances. Methods: We retrospectively evaluated a cohort of 66 unselected patients with idiopathic thrombocytopenic purpura, who received 140 courses of IVIG therapy. Acute renal failure (ARF), hyponatremia and hyperkalemia, as potential complications of IVIG therapy, were assessed from 100 IVIG courses with sufficient data for analysis. Results: Thirteen out of 100 (13%) IVIG courses in 10 (15%) patients were complicated with ARF. Risk factors included advanced age, pre-existing renal impairment, use of diuretics and the presence of diabetes mellitus. All patients recovered renal function 1–2 weeks after IVIG infusion. Serum sodium (sNa) fell by 5.7 and 2.7 mmol/l (p < 0.01) in patients with and without ARF, respectively. Correspondingly, serum potassium increased by 0.7 and 0.23 mmol/l (p < 0.01). There was a strong inverse correlation (r = –0.308; p < 0.01) between changes in sNa and creatinine. Changes in serum potassium could be independently predicted by changes in both sNa and creatinine (R² = 0.11; p < 0.01). These data suggested that both hyponatremia and hyperkalemia were (a) due to the translocational effect of the osmotic load of sucrose, and (b) largely depended on the extent of IVIG nephropathy. Conclusion: In our series, ARF attributable to IVIG therapy, although not rare, was usually mild and fully reversible. High-risk patients were more susceptible to IVIG-related renal complications. Translocational hyponatremia and hyperkalemia following IVIG therapy, although unimportant in patients with normal renal function, may be of clinical significance in patients with severely compromised renal function, resulting in impaired sucrose excretion.

“Man-in-the-barrel” syndrome as delayed manifestation of extrapontine and central pontine myelinolysis: Beneficial effect of intravenous immunoglobulin

“Man-in-the-barrel” syndrome has been rarely described following osmotic myelinolysis. We report a case of a 45-year-old woman admitted with septicemia and severe hyponatremia. She presented with a “man-in-the-barrel” syndrome which developed more than 10 days after rapid correction of the hyponatremia. There was radiological evidence of central pontine and extrapontine myelinolysis. Three days after completing a course of intravenous immunoglobulin therapy (0.4 g/kg body weight/day for 5 days) there was considerable improvement (Expanded Disability Status Scale score improved 30%). This case, reported for its peculiar mode of development, unusual presentation and challenging therapeutic response to intravenous immunoglobulin, highlights the enigmatic and unpredictable aspects of osmotic myelinolysis.

Linear IgA bullous disease limited to the eye: a diagnostic dilemma : Response to Intravenous Immunoglobulin therapy

Purpose To report on a diagnostic dilemma and treatment challenge in a patient with chronic cicatrizing conjunctivitis without involvement of skin and other mucous membranes persisting for 6 years and not responding to topical and systemic steroids. Design Interventional case report. Methods We performed direct immunofluorescence of the conjunctiva with fluorescein-conjugated rabbit antihuman antibodies against immunoglobulin A, G, and M, complement 3 component, and fibrinogen. To investigate the presence of circulating antibodies in patient’s serum, indirect immunofluorescence using normal human conjunctiva, normal human skin, and monkey esophagus as substrate was done. In addition, we did immunoblot analysis using normal human epidermis as substrate to determine the molecular weight of an antigen. The patient was treated with intravenous immunoglobulin (IVIg). The correlation between the titer of circulating antibodies and the activity of conjunctival inflammation at various intervals during the course of IVIg therapy was demonstrated by immunoblot assay with serial dilutions of the patient’s serum. The highest dilution at which the binding was visible was considered the titer. Results Direct immunofluorescence of the conjunctiva and indirect immunofluorescence with both salt split skin and conjunctiva as substrate disclosed linear deposition of immunoglobulin A (IgA) at the epithelial basement membrane. Immunoblot analysis demonstrated the presence of IgA circulating antibodies in patient’s serum directed against a 97kDa protein in human epidermis. A continuous decrease in the titer of these antibodies correlating to improvement of clinical symptoms was observed during IVIg therapy. Conclusions Use of a nonconventional diagnostic tool (immunoblot analysis), in addition to conventional immunohistologic studies, might be helpful in establishing the diagnosis of patients with chronic cicatrizing conjunctivitis. On the basis of results of these laboratory tests and clinical presentation, we believe that this patient has linear IgA bullous disease limited to the eye. IVIg therapy decreased the titer of circulating antibodies and induced a remission in this patient.

Influence of intravenous immunoglobulin therapy on serum levels of anti-ß4 antibodies in ocular cicatricial pemphigoid: A correlation with disease activity

Purpose. To determine any correlation between activity of ocular cicatricial pemphigoid and titer of anti-ß4 antibodies, and any effect of intravenous immunoglobulin (IVIg) therapy on serum levels of anti-ß4 antibodies followed over a 12 month period, using the specific immunoblot assay (IBA). Patients and methods. Eight patients diagnosed with OCP and treated with IVIg as monotherapy were included in the study. Each patient was treated with at least two immunosuppressive agents prior to the institution of IVIg. The presence of anti-ß4 antibodies in the patients’ sera was detected by IBA using bovine gingival lysate (BGL) or tumor cell line lysate (TCL) as substrates. The activity of OCP was graded based on the conjunctival injection using a scale of zero to four in increments of 0.5 at monthly intervals. To determine the correlation between serum levels of circulating autoantibody and the patients’ conjunctival disease activity, the titer of anti-ß4 antibodies was determined at monthly intervals during the course of IVIg therapy. Blood samples were drawn prior to administration of IVIg infusion. The titer was determined by IBA, using serial dilutions of the patients’ sera. The highest dilution at which the binding was visible was considered the titer. The dose of IVIg administered was approximately 2–3 g/kg/cycle. The infusion cycles were initially given at monthly intervals, approximately 70 grams daily over four hours for three consecutive days. As clinical improvement was observed, the interval between the cycles was increased, but the dose of IVIg remained the same for each cycle. To study whether the IVIg has an effect on other antibodies, monthly serum levels of antibodies to tetanus toxoid were measured by ELISA. Results. We observed a continuous decrease in mean monthly titer of circulating anti-ß4 antibodies in the patients’ sera during IVIg therapy. A decrease in conjunctival inflammation during the course of IVIg was documented by monthly examination in every patient and paralleled the decrease in titer of anti-ß4 antibodies. Since the fifth month of IVIg therapy, the mean conjunctival inflammation remained less than 0.5, suggesting a clinical remission of OCP. Titers of antibodies to tetanus toxoid remained unchanged during the study period. Conclusions. This preliminary study demonstrates a correlation between serum titers of anti-ß4 antibodies and clinical disease activity in patients with OCP. In addition, the study shows that the use of IVIg is associated with a decrease in the serum titer of anti-ß4 antibodies.

Primary immunodeficiency diseases in children treated in the Children's Memorial Hospital, Poland.

One hundred and three cases of primary immunodeficiency diseases were diagnosed among children suffering mainly from chronic and severe infections in the period 1980-1987. Predominantly antibody defects were recognized in 48 patients (46.6%), combined immunodeficiencies in 36 patients (35%), phagocytic disorders in 12 patients (11.6%), complement defects in 6 patients (5.8%), and cell-mediated disease (Di George syndrome) in 1 patient. Allergic complications were observed in 25 patients (24.2%) and malignancy-in 3 patients (2.9%). More detailed immunological studies were performed in children with X-linked agammaglobulinemia in the course of intravenous immunoglobulin therapy and in children with ataxia telangiectasia.