Baseline Characteristics and Predictive Factors of Intravenous Immunoglobulin Response in Drug and Device Refractory Gastroparesis Symptoms.

INTRODUCTION: Intravenous immunoglobulin (IVIG) has been shown in a small pilot series to be helpful for some patients with gastroparesis that is refractory to drugs, devices, and surgical therapies. Many but not all patients have serologic neuromuscular markers. We hypothesize that those patients with serologic markers and/or longer duration of therapy would have better responses to IVIG. MATERIALS AND METHODS: We studied 47 patients with a diagnosis of gastroparesis and gastroparesis-like syndrome that had all failed previous therapies including available and investigational drugs, devices, and/or pyloric therapies. Patients had a standardized 12-week course of IVIG, dosed as 400 mg/kg per week intravenously. Symptom assessment was done with Food and Drug Administration (FDA) compliant traditional patient-reported outcomes. Success to IVIG was defined as 20% or greater reduction in average symptom scores from baseline to the latest evaluation. RESULTS: Fourteen patients (30%) had a response, and 33 (70%) had no response per our definition. Patients responding had a higher glutamic acid decarboxylase 65 positivity (64% vs. 30%, P =0.049, missing=3) and longer duration of therapy (>12 wk/continuous: 86% vs. 48%, P =0.09). CONCLUSIONS: In this moderately sized open-label series of refractory patients with gastroparesis symptoms treated with IVIG, 30% of patients responded. While serologic markers and extended therapies show a trend to greater response, neither was statistically significant, except for glutamic acid decarboxylase 65 which showed a higher positivity rate in responders. We conclude that a clinical trial of IVIG may be warranted in severely refractory patients with gastroparesis symptoms.

Cajal Cell Counts are Important Predictors of Outcomes in Drug Refractory Gastroparesis Patients With Neurostimulation.

BACKGROUND AND AIMS: Cajal cells serve as the pacemaker cells of the gastrointestinal tract and regulates peristalsis. On the baisis of that fact, it has been hypothesized that a decrease in Cajal cells can lead to gastroparesis and other motility issues. Treatment with medications has a limited efficacy and most resort to gastric electrical stimulation (GES) devices for symptomatic relief. We believe that the number of Cajal cells present is directly proportional to symptomatic relief with GES. MATERIALS AND METHODS: Twenty-three (white female) subjects were recruited from the gastric motility clinic University of Mississipi for this study with the criteria of drug refractory gastropersis. Symptoms were measured using Likert scale and gastric emptying times were measured pre-GES and post-GES. Serosal electrogram measurements were recorded during surgical placement of permanent electrical stimulator under various modes. Cajal cell count scoring via immunohistochemistry were performed during the implantaion of the GES. RESULTS: The data were grouped in 2 categories based on the Cajal cells that is ≥2.00 and <2.00. Subjects with higher Cajal cells reported a statiscially improvement in gastroperesis symptoms. Significant differences were also noted in the first hour gastric emptying study. The mean group difference is 17.5 (95% confidence interval, 1.41-33.58; P=0.035). Serosal amplitude differences were noted being significantly higher in the group with ≥2 cajal cells. CONCLUSIONS: Electrograms obtained after GES demonstrates immediate improvement in gastric electrical activity and gastroparesis symptoms in patients with relatively higher Cajal cell counts when compared with patients with extensive loss of Cajal cells.

Immunomodulation for treatment of drug and device refractory gastroparesis.

OBJECTIVE: Patients with generalized autoimmune dysautonomia may also present with gastroparesis. Immune dysfunction in such patients can be evaluated using antibodies to glutamic acid decarboxylase (GAD) and full thickness biopsy of stomach. In this study, we utilize immunotherapy for treatment of drug and Gastric Electrical Stimulation (GES) resistant gastroparetic patients with evidence of neuroinflammation on full thickness gastric biopsy and had positive GAD65 autoantibodies. MATERIAL AND METHODS: We conducted a retrospective chart review of 11 female patients with drug and device resistant gastroparesis. Patients were treated for a total of 8-12 weeks with either intravenous immunoglobulin (IVIg), or combined mycophenolate mofetil (MM) and methylprednisolone, or only MM. Patients were excluded if they had previous side effects from steroid therapy, low scores on dual-energy X-ray absorptiometry (DEXA) scan results, immune-compromised conditions with infections like tuberculosis and zoster. Symptoms of nausea, vomiting, abdominal pain, early satiety/anorexia, bloating and total symptom score (TSS) as reported by the patients were recorded before and after the treatment at a follow up visit 2 to 16 weeks after initiation of therapy. RESULTS: Maximum symptom improvement was seen in patients treated with IVIg (67%). 6 patients (55%) had improvement in vomiting, whereas 5 patients (45%) had improvements in nausea, abdominal pain and bloating. CONCLUSIONS: Immunomodulatory therapy shows positive outcomes in improving vomiting symptom in some gastroparetic patients who have coexisting positive autoimmune profiles. This preliminary data suggests the need for further investigations in immunotherapy targeted to patients with gastroparetic symptoms refractory to approved drug and device therapies.

Congenital bilateral vocal fold paralysis and Charcot-Marie-Tooth disease.

We present the case of a patient with Charcot-Marie-Tooth disease (CMT) type 1 with congenital bilateral vocal fold paralysis in order to emphasize the treatment options and long-term outcome. The case is reviewed with regard to presentation, differential diagnosis, and treatment. We also reviewed the literature to determine the frequency of congenital and childhood presentations of bilateral vocal fold paralysis associated with CMT, most specifically CMT type 1. We found only 14 children reported to have bilateral vocal fold paralysis associated with CMT, and only 1 of these cases was associated with CMT type 1. None of these patients had congenital vocal fold paralysis. Because of the degenerative nature of the disease, our patient underwent endoscopic cordotomy to avoid tracheotomy. We conclude that CMT should be included in the differential diagnosis in evaluating neonates with bilateral vocal fold paralysis. If CMT is definitively diagnosed, it could alter the course of treatment.

An uncommon illness with a rare presentation: neurosurgical management of ADEM with tumefactive demyelination in children.

PURPOSE: This study determined the statewide incidence and prevalence of acute disseminated encephalomyelitis (ADEM) and examined the course of three pediatric patients treated for tumefactive demyelination (TD) at the Blair E. Batson Children's Hospital. METHODS: Analyses of ICD-9-CM code hospital records and clinical database were conducted. RESULTS: From 2001 through 2007 the incidence in pediatric patients under 20 years was 0.4/100,000/year, with a prevalence of 8.6/100,000 during 2008. Three patients presented with TD. Case 1 had a 3-week history of ataxia and diplopia; case 2 presented with a sudden onset of coma, while the third child had a 4-month history of increasing lethargy and clumsiness in all extremities. Cerebrospinal fluid examinations were nondiagnostic. MRI examinations revealed asymmetric T2/fluid-attenuated inversion recovery hyperintensity within the pons (case 1), a large heterogenously enhancing temporal lobe mass, with extensive edema (case 2), and multiple small brain lesions with occasional ring enhancement (case 3). In case 1, intralesional MR spectroscopy demonstrated changes consistent with ADEM. Case 2 required intracranial monitoring, and medical treatment to control elevated ICP. Cases 2 and 3 underwent cortical biopsies that revealed ADEM. All three patients improved with corticosteroid therapy. At a minimum of 15 months follow-up, cases 1 and 2 showed resolution of deficits and MRI lesions, while the third patient demonstrated additional MRI lesions and increasing paraparesis. CONCLUSIONS: These cases demonstrate that appropriate neuroradiological evaluation, treatment of acutely elevated ICP, and brain biopsy can play critical roles in the management of children with undiagnosed ADEM and TD.