PubMed Health⌕ Search

Biomedical subjects

Thomas H Brannagan

Publications and source records attributed to Thomas H Brannagan.

16 recordsLinked to original sources
PubMed2026

Impact of Baseline Polyneuropathy Severity on Eplontersen Efficacy in the NEURO-TTRansform Clinical Trial.

BACKGROUND AND AIMS: In the NEURO-TTRansform clinical trial (NCT04136184), eplontersen improved neuropathy impairment and quality of life (QoL) through Week 66 versus the NEURO-TTR historical placebo in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This analysis assessed the impact of baseline ATTRv-PN severity on eplontersen response in patients from NEURO-TTRansform. METHODS: This post hoc analysis grouped patients into tertiles by baseline Neuropathy Impairment Score (NIS): T1 (least baseline impairment: 3.5 to <&#x2009;27.5; n&#x2009;=&#x2009;67), T2 (27.5 to <&#x2009;55.0; n&#x2009;=&#x2009;67), and T3 (55.0 to <&#x2009;127.8; n&#x2009;=&#x2009;66). Outcomes assessed were neuropathy impairment (modified NIS+7 [mNIS+7] and NIS, Neuropathy Symptom and Change, Polyneuropathy Disability), QoL (Norfolk QoL-Diabetic Neuropathy), physical functioning (36-Item Short-Form Health Survey Physical Component Summary), nutritional status (modified body mass index), and serum transthyretin levels; these were compared with NEURO-TTR historical placebo. Autonomic dysfunction (Composite Autonomic Symptom Score-31), disability (Rasch-built Overall Disability Scale), and walking speed (10-Meter Walk Test) were also assessed. Final assessments were carried out following 65/66 or 81/85&#x2009;weeks of treatment. RESULTS: Mean mNIS+7 composite scores were maintained over 85&#x2009;weeks with eplontersen (changes from baseline of -4.5 [T1], -1.3 [T2], and -2.6 [T3] points). Other disease parameter scores were similarly maintained or improved with eplontersen. Patients receiving placebo experienced disease worsening across outcomes. T1 mean disease scores were typically better than in T2 and T3. INTERPRETATION: Consistent, sustained benefits of eplontersen were observed regardless of baseline ATTRv-PN severity. These findings strengthen the importance of early treatment initiation for patients with ATTRv-PN across the disease spectrum.

Humans↗
PubMed2007

Chronic inflammatory demyelinating polyneuropathies: current treatment strategies.

Chronic inflammatory demyelinating polyradiculopathy (CIDP), considered an immune-mediated disease, is likely under-recognized and under-treated due to its heterogeneous presentation and the limitations of clinical, serologic, and electrophysiologic diagnostic criteria. Despite these limitations, early diagnosis and treatment is important in preventing irreversible axonal loss and improving functional recovery. Primary treatment modalities include intravenous immunoglobulin and plasmapheresis, for which there is randomized, double-blind, placebo-controlled evidence. In addition, despite less definitive published evidence of efficacy, corticosteroids are considered standard therapies because of their long history of use. Studies have failed to demonstrate a difference in efficacy among these three treatments; consequently, the choice is usually based on availability and side-effect profile. A number of chemotherapeutic and immunosuppressive agents have also shown to be effective in treating CIDP but significant evidence is lacking; therefore, these agents are primarily used in conjunction with other modalities. Regardless of the treatment choice, long-term therapy is required to maintain a response and prevent relapse.

Disease Management↗
PubMed2006

High-dose cyclophosphamide without stem cell rescue for refractory multifocal motor neuropathy.

Patients with multifocal motor neuropathy (MMN) respond to intravenous immune globulin (IVIg) and cyclophosphamide, although the benefit is not sustained. High-dose cyclophosphamide can induce a remission in patients with autoimmune diseases, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We describe a patient with refractory MMN who improved with high-dose cyclophosphamide (50 mg/kg for 4 days) without stem cell rescue. Following treatment she discontinued IVIg. At a 6-month examination, her strength had improved and she had regained the ability to write. High-dose cyclophosphamide may be a successful treatment for patients with MMN refractory to other therapies.

Antineoplastic Agents↗
PubMed2006

Diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated acquired polyneuropathy that may lead to disability. CIDP is characterized by an autoimmune attack against peripheral nervous system myelin, by cellular and humoral mechanisms. Early diagnosis and treatment may yield better functional recovery, probably by minimizing secondary axonal loss from a primary demyelinating insult. Intravenous immunoglobulin and plasmapheresis are considered standard-of-care therapy in CIDP, based on randomized, double-blinded, placebo-controlled evidence. Corticosteroids, despite less robust evidence, are also considered standard therapy for CIDP. Other nonstandard therapies may work in refractory patients. These include azathioprine, cyclophosphamide, cyclosporine A, etanercept, interferon-alpha 2a, mycophenolate mofetil, and tacrolimus. Emerging therapies include interferon-beta 1a, rituximab, and high-dose cyclophosphamide without stem-cell rescue. Because most patients will require prolonged therapy, long-term side effects are important considerations.

Journal Article↗
PubMed2005

Small-fiber neuropathy/neuronopathy associated with celiac disease: skin biopsy findings.

BACKGROUND: Celiac disease (CD) is increasingly recognized in North America and is associated with a peripheral neuropathy. OBJECTIVE: To report the clinical characteristics and skin biopsy results in patients with CD and small-fiber neuropathy symptoms. DESIGN: Case series. SETTING: Academic peripheral neuropathy clinic. PATIENTS: Eight patients with CD and neuropathy symptoms. Intervention Three-millimeter punch biopsy using the panaxonal marker protein gene product 9.5 to assess epidermal nerve fiber (ENF) density and a gluten-free diet. MAIN OUTCOME MEASURE: Clinical data and ENF density. RESULTS: All patients had asymmetric numbness and paresthesias. Three had more prominent involvement of hands than feet, and 3 had facial numbness. Celiac disease was diagnosed in 5 after their neuropathy began. The following serum antibody levels were elevated: tissue transglutaminase (n = 6), IgA gliadin (n = 4), and IgG gliadin (n = 7). Results of nerve conduction studies were normal in 7 patients. One patient had mildly reduced sural amplitudes. The ENF density was reduced in 5 patients. The ENF density was at the low limit of the normal range in 3 additional patients, 2 of whom had morphologic changes in axons. Three patients had decreased ENF density at the thigh or forearm, which was more severe than at the distal leg, compatible with a non-length-dependent process. Four reported improvement with a gluten-free diet. One had no improvement after 4 months. Symptoms developed in 2 while receiving a gluten-free diet. CONCLUSIONS: Patients with CD may have a neuropathy involving small fibers, demonstrated by results of skin biopsy. The pattern of symptoms, with frequent facial involvement and a non-length-dependent pattern on skin biopsy findings, suggests a sensory ganglionopathy or an immune-mediated neuropathy. Improvement of symptoms in some patients after initiating a gluten-free diet warrants further study.

Celiac Disease↗
PubMed2005

Rituximab treatment of an IgM monoclonal autonomic and sensory neuropathy.

Rituximab, a monoclonal antibody against B-cell membrane marker CD-20, is an effective treatment for immunoglobulin M (IgM) monoclonal anti-myelin-associated glycoprotein (MAG) neuropathies. We report a patient with an autonomic and painful sensory neuropathy associated with an IgM lambda monoclonal gammopathy, responsive to rituximab. Treatment resulted in a decline in total IgM and improvement in the patient's painful neuropathy and dysautonomia. Rituximab may be an effective and tolerable treatment for autonomic and sensory neuropathy associated with IgM monoclonal gammopathy.

Aged↗
PubMed2005

High-dose cyclophosphamide results in long-term disease remission with restoration of a normal quality of life in patients with severe refractory chronic inflammatory demyelinating polyneuropathy.

We previously reported the improvement of clinical parameters in severe, refractory chronic inflammatory demyelinating polyneuropathy (CIDP) following high-dose cyclophosphamide therapy. Here, we examine effects of this therapy on quality of life, report long-term clinical follow-up, and include new data on a fifth patient. Patients completed The Medical Outcomes Short Form 36 to assess quality of life impact. Pretherapy and post-therapy scores were compared with the Wilcoxon Signed Ranks Test. Patient's post-therapy scores were compared with the normal United States population. Functional status was assessed with the Modified Rankin score. Strength was assessed using a summated MRC strength. Nerve conduction studies were conducted using standard techniques with supramaximal stimulation. The median follow-up for the five patients is 2.9 (range: 1.6-4.8) years. The first four patients remain off all immunomodulatory medications. In six of the eight quality of life scales measured, patients enjoyed clinically significant improvement. Their overall strength increased by a median change of 10 (range: -1 to 20); their overall Modified Rankin score increased by a median of 3 (range: 0-4), and their summated compound motor action potential amplitudes increased by a mean of 3.69 mV (range: 0.156-7.83). Patient 5 has had stabilization of motor strength. High-dose cyclophosphamide can markedly improve functionality and quality of life for patients with severe refractory CIDP.

Adult↗
PubMed2004

Characterization of neuropathies associated with elevated IgM serum levels.

BACKGROUND: In contrast to the IgM monoclonal gammopathies the neuropathy associated with polyclonal IgM gammopathy has not been well characterized. OBJECTIVE: To characterize the neuropathy in patients with elevated serum IgM. DESIGN: Retrospective review. SETTING: Academically based neuropathy center. PATIENTS: 45 patients with elevated quantitative immunoglobulin M were identified. MAIN OUTCOME MEASURES: Patients are described with regard to clinical phenotype, electrodiagnostic features of demyelination or focality, presence of IgM monoclonal gammopathy, and presence of autoantibody activity. RESULTS: Elevated IgM levels occurred in 45 (11.5%) of 391 patients. Of these, 24 (53%) had polyclonal gammopathy and 21 (47%) had an IgM monoclonal gammopathy. Anti-nerve antibodies occurred in 14/21 (67%) of patients with monoclonal gammopathy, as compared to 1/24 (4%) with polyclonal gammopathy. Clinically, most patients in all groups had a predominantly large fiber sensory neuropathy. Thirty patients underwent electrodiagnostic testing. Of these, 22/30 (73%) fulfilled at least one published criteria for CIDP, including 92% of the monoclonal gammopathy patients and 59% of the polyclonal gammopathy patients. Fifteen of the 30 patients had evidence of focality or multifocality, with 14 of these 15 showing evidence of demyelination. CONCLUSIONS: Monoclonal and polyclonal IgM patients have similar distributions of neuropathy phenotypes. Neuropathy in association with elevated serum IgM, with or without monoclonal gammopathy or autoantibody activity, is more likely to be demyelinating or multifocal. Serum quantitative IgM level and immunofixation in neuropathy patients may aid in identification of an immune mediated or a demyelinating component.

Antibodies, Monoclonal↗
PubMed2004

Gene expression profiling in chronic inflammatory demyelinating polyneuropathy.

Gene expression in archived frozen sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) was compared to that in vasculitic nerve biopsies (VAS) and to normal nerve (NN) by DNA microarray technology. Hierarchical clustering analysis demonstrated distinct gene expression patterns distinguishing these disease groups. Of particular interest were: (1) Tachykinin precursor 1, which may be involved in pain mediation; (2) Stearoyl-CoA-desaturase, which may be a marker for remyelination and (3) the Allograft Inflammatory Factor 1 (AIF-1), a modulator of immune response during macrophage activation. Differential gene expression may help distinguish between CIDP, VAS and NN in sural nerve biopsies and identify genes that may be involved in disease pathogenesis.

Adult↗
PubMed2004

Sensory CIDP presenting as cryptogenic sensory polyneuropathy.

The objective of this study was to report that patients with chronic inflammatory demyelinating polyneuropathy (CIDP) can present with a clinical picture of cryptogenic sensory neuropathy. Patients with distal sensory neuropathy and electrodiagnostic studies that are minimally abnormal or consistent with an axonal pathology are usually diagnosed as having cryptogenic sensory neuropathy if no cause for neuropathy can be found. Some of these patients, however, may have sensory CIDP. We reviewed the records of eight patients with CIDP, diagnosed by sural nerve biopsy, who presented with sensory neuropathy and electrodiagnostic studies that were minimally abnormal or revealed changes consistent with axonal neuropathy. All patients reported distal numbness and paresthesias and, on examination, had predominantly large fiber distal sensory loss and normal muscle strength. In most patients, deep tendon reflexes were reduced or absent. Sural nerve biopsies in all patients were consistent with chronic myelinopathy, with quantitative teased fiber analysis revealing segmental remyelination in 13-40% of the fibers. The four patients who received IVIg therapy had improved sensation and gait. Of the remaining four patients, one is being followed, one had spontaneous remission, one was lost to follow-up, and one, with contraindications to therapy, reported disease progression. Sensory CIDP may present as cryptogenic sensory polyneuropathy with normal or axonal electrophysiologic features. Sural nerve biopsy should be considered in patients with progressive, predominantly large fiber sensory neuropathy of otherwise unknown etiology, as they may have sensory CIDP that responds to therapy.

Adult↗
PubMed2004

Neuropathy and cognitive impairment following vaccination with the OspA protein of Borrelia burgdorferi.

Neurological syndromes that follow vaccination or infection are often attributed to autoimmune mechanisms. We report six patients who developed neuropathy or cognitive impairment, within several days to 2 months, following vaccination with the OspA antigen of Borrelia burgdorferi. Two of the patients developed cognitive impairment, one chronic inflammatory demyelinating polyneuropathy (CIDP), one multifocal motor neuropathy, one both cognitive impairment and CIDP, and one cognitive impairment and sensory axonal neuropathy. The patients with cognitive impairment had T2 hyperintense white matter lesions on magnetic resonance imaging. The similarity between the neurological sequelae observed in the OspA-vaccinated patients and those with chronic Lyme disease suggests a possible role for immune mechanisms in some of the manifestations of chronic Lyme disease that are resistant to antibiotic treatment.

Adult↗
PubMed2003

HIV-associated Guillain-Barré syndrome.

Human immunodeficiency virus-associated Guillain-Barré syndrome (HIV-GBS) has been reported since 1985. Based on previous reports, this neuropathy typically occurs early in HIV infection, even at seroconversion, prior to developing acquired immunodeficiency syndrome (AIDS). Patients with GBS and CD4 counts of <50 have been proposed to have cytomegalovirus (CMV) infection and empiric gancyclovir is recommended. We reviewed medical records of 10 patients with HIV-GBS at five hospitals from 1986 to 1999. The mean CD4 count was 367/mm(3) (range 55-800). GBS was the first symptom of HIV infection in three patients. Four patients had AIDS with CD4 counts ranging from 55 to 190. CSF white blood cell (WBC) was 0 wbc/mm(3) in four patients, 2-10 wbc/mm(3) in three and 11-17 wbc/mm(3) in two. Three had recurrent weakness from 9 weeks to 4 years after the onset of symptoms, which persisted. HIV-GBS occurs in early and late stages of HIV infection, and may follow the onset of AIDS. No patients were seen with severe immunosuppression (CD4<50). A mild cerebrospinal fluid (CSF) pleocytosis in GBS suggests HIV infection, but is frequently absent. Compared to HIV-negative people, HIV-GBS may be associated with more frequent recurrent episodes or the development of CIDP.

Adult↗
PubMed2003

Comparison of electrodiagnostic abnormalities and criteria in a cohort of patients with chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: Current electrodiagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) are research oriented favoring specificity over sensitivity. Application of such criteria in clinical practice may miss the diagnosis in potentially treatable patients. OBJECTIVES: To analyze the electrophysiologic abnormalities in a cohort of patients with clinically defined CIDP, to compare these data with published electrodiagnostic criteria, and to identify a set of abnormalities that is shared by all patients with CIDP. DESIGN: Retrospective medical record review. SETTING: Academically based neuromuscular clinic. Patients Fifteen patients with clinically diagnosed relapsing sensorimotor CIDP. INTERVENTIONS: Administration of intravenous immunoglobulin or prednisone. MAIN OUTCOME MEASURES: Electrodiagnostic studies. RESULTS: All patients had electrodiagnostic abnormalities in at least 3 nerves with possible partial conduction block or demyelinating range abnormalities in at least 1 nerve. The diagnostic sensitivities of 5 published CIDP criteria were as follows: the Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force (40%), Saperstein et al (47%), Nicolas et al (53%), Hughes et al for the Inflammatory Neuropathy Cause and Treatment Group (60%), and Thaisetthawatkul et al (70%). CONCLUSIONS: Current electrodiagnostic criteria for CIDP are insensitive and may fail to diagnose the condition in a substantial number of patients. More inclusive criteria that allow identification of patients in routine clinical practice are needed.

Action Potentials↗
PubMed2002

Intravenous gammaglobulin (IVIg) for treatment of CIDP and related immune-mediated neuropathies.

Intravenous immune globulin (IVIg) is considered an effective and safe treatment for autoimmune neuropathies, especially in comparison to the alternative treatments such as corticosteroids, chemotherapy, and plasmapheresis. Patients are frequently given a standard induction dose of 2 g/kg, which may be followed by maintenance therapy as needed. Mild infusion-related reactions are frequent but these can often be controlled by slowing the infusion rate or by symptomatic medications. Serious adverse effects are rare and can include thromboembolic events, renal failure, anaphylaxis, or septic meningitis. Patients with IgA deficiency are at risk for anaphylaxis. Immobility, increased serum viscosity, and preexisting vascular disease can increase the risk for thromboembolic events. Preexisting renal insufficiency or the use of sucrose-containing IVIg preparations can increase the risk for renal failure, and patients with migraine are at risk for development of aseptic meningitis. Screening patients for risk factors that predispose to development of adverse events may reduce the incidence of complications.

Drug Administration Schedule↗