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David R Cornblath

Publications and source records attributed to David R Cornblath.

10 recordsLinked to original sources
PubMed2006

Recent advances in HIV neuropathy.

PURPOSE OF REVIEW: To describe recent advances in HIV neuropathy. RECENT FINDINGS: Epidemiologic studies since highly active antiretroviral therapy was introduced have shown that the incidence of HIV-associated distal sensory polyneuropathy is reduced. Studies have also shown the relationship between distal sensory polyneuropathy and the use of neurotoxic antiretroviral drugs. Skin punch biopsy for assessment of epidermal nerve fiber density is valuable both for diagnosis of distal sensory polyneuropathy and as a predictor of the condition occurring in the future. An in-vitro model of antiretroviral toxic neuropathy showed that dideoxynucleoside analogues that cause neuropathy exert direct mitochondrial toxicity that is not mediated indirectly through the inhibition of DNA polymerase-gamma. HIV envelope protein gp120 exerts axonal toxicity directly or indirectly via perineuronal Schwann cells. A feline model of HIV, infection of neonatal cats with the feline immunodeficiency virus, showed development of peripheral neuropathy characterized by loss of epidermal innervation. SUMMARY: While epidemiological studies of HIV-associated peripheral neuropathy continue to provide useful information, pathogenic studies are moving forward. Animal models of the disease will allow researchers to 'manipulate' the system. It is hoped that these types of studies will translate to an improved understanding of the pathogenesis of HIV-associated neuropathies leading to better treatments.

Antiretroviral Therapy, Highly Active↗
PubMed2005

Guillain-Barré syndrome.

Guillain-Barré syndrome consists of at least four subtypes of acute peripheral neuropathy. Major advances have been made in understanding the mechanisms of some of the subtypes. The histological appearance of the acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype resembles experimental autoimmune neuritis, which is predominantly caused by T cells directed against peptides from the myelin proteins P0, P2, and PMP22. The role of T-cell-mediated immunity in AIDP remains unclear and there is evidence for the involvement of antibodies and complement. Strong evidence now exists that axonal subtypes of Guillain-Barré syndrome, acute motor axonal neuropathy (AMAN), and acute motor and sensory axonal neuropathy (AMSAN), are caused by antibodies to gangliosides on the axolemma that target macrophages to invade the axon at the node of Ranvier. About a quarter of patients with Guillain-Barré syndrome have had a recent Campylobacter jejuni infection, and axonal forms of the disease are especially common in these people. The lipo-oligosaccharide from the C jejuni bacterial wall contains ganglioside-like structures and its injection into rabbits induces a neuropathy that resembles acute motor axonal neuropathy. Antibodies to GM1, GM1b, GD1a, and GalNac-GD1a are in particular implicated in acute motor axonal neuropathy and, with the exception of GalNacGD1a, in acute motor and sensory axonal neuropathy. The Fisher's syndrome subtype is especially associated with antibodies to GQ1b, and similar cross-reactivity with ganglioside structures in the wall of C jejuni has been discovered. Anti-GQ1b antibodies have been shown to damage the motor nerve terminal in vitro by a complement-mediated mechanism. Results of international randomised trials have shown equivalent efficacy of both plasma exchange and intravenous immunoglobulin, but not corticosteroids, in hastening recovery from Guillain-Barré syndrome. Further research is needed to discover treatments to prevent 20% of patients from being left with persistent and significant disability.

Adult↗
PubMed2005

Supportive care for patients with Guillain-Barré syndrome.

A multidisciplinary consensus group searched MEDLINE from 1966 to May 2003, extracted relevant references, and prepared recommendations on supportive care for Guillain-Barré syndrome. In the absence of randomized controlled trials, we agreed on recommendations by consensus based on observational studies and expert opinion. In the acute phase in bed-bound adult patients, the group recommended the use of heparin and graduated pressure stockings to prevent deep vein thrombosis, monitoring for blood pressure, pulse, autonomic disturbances, and respiratory failure, and the timely institution of artificial ventilation and tracheostomy. Pain management is difficult, but carbamazepine or gabapentin may help. The cautious use of narcotic analgesics may be needed. Disabled patients should be treated by a multidisciplinary rehabilitation team and should receive an assistive exercise program. Persistent fatigue following Guillain-Barré syndrome is common and may be helped by an exercise program. Because of a very small and possibly only theoretical increase in the risk of recurrence following immunization, the need for immunization should be reviewed on an individual basis. More research is needed to identify optimal methods for all aspects of supportive care.

Autonomic Nervous System Diseases↗
PubMed2005

Rhabdomyolysis: an evaluation of 475 hospitalized patients.

Rhabdomyolysis is a common and potentially lethal clinical syndrome that results from acute muscle fiber necrosis with leakage of muscle constituents into blood. Myoglobinuria is the most significant consequence, leading to acute renal failure (ARF) in 15%-33% of patients with rhabdomyolysis. Rhabdomyolysis occurs from inherited diseases, toxins, muscle compression or overexertion, or inflammatory processes, among other disorders. In some cases, no cause is found. We describe 475 patients from the Johns Hopkins Hospital inpatient records between January 1993 and December 2001 for the following discharge diagnosis codes: myoglobinuria, rhabdomyolysis, myopathy, toxic myopathy, malignant hyperthermia, neuroleptic malignant syndrome, and polymyositis. Of 1362 patients, 475 patients with an acute neuromuscular illness with serum creatine kinase (CK) more than 5 times the upper limit of normal (>975 IU/L) were included. Patients with recent myocardial infarction or stroke were excluded. The etiology was assigned by chart review. For all, the highest values of serum CK, serum creatinine and urine myoglobin, hemoglobin, and red blood cells were recorded. Forty-one patients had muscle biopsy within at least 2 months from the onset of rhabdomyolysis.Of the 475 patients, 151 were female and 324 were male (median age, 47 yr; range, 4-95 yr). Exogenous toxins were the most common cause of rhabdomyolysis, with illicit drugs, alcohol, and prescribed drugs responsible for 46%. Among the medical drugs, antipsychotics, statins, zidovudine, colchicine, selective serotonin reuptake inhibitors, and lithium were the most frequently involved. In 60% of all cases, multiple factors were present. In 11% of all cases, rhabdomyolysis was recurrent. Underlying myopathy or muscle metabolic defects were responsible for 10% of cases, in which there was a high percentage of recurrence, only 1 etiologic factor, and a low incidence of ARF. In 7%, no cause was found. ARF was present in 218 (46%) patients, and 16 died (3.4%). A linear correlation was found between CK and creatinine and between multiple factors and ARF, but there was no correlation between ARF and death or between multiple factors and death. Urine myoglobin detected by dipstick/ultrafiltration was positive in only 19%. Toxins are the most frequent cause of rhabdomyolysis, but in most cases more than 1 etiologic factor was present. Patients using illicit drugs or on prescribed polytherapy are at risk for rhabdomyolysis. The absence of urine myoglobin, by qualitative assay, does not exclude rhabdomyolysis. With appropriate care, death is rare.

Acute Disease↗
PubMed2004

DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4).

Juvenile amyotrophic lateral sclerosis (ALS4) is a rare autosomal dominant form of juvenile amyotrophic lateral sclerosis (ALS) characterized by distal muscle weakness and atrophy, normal sensation, and pyramidal signs. Individuals affected with ALS4 usually have an onset of symptoms at age <25 years, a slow rate of progression, and a normal life span. The ALS4 locus maps to a 1.7-Mb interval on chromosome 9q34 flanked by D9S64 and D9S1198. To identify the molecular basis of ALS4, we tested 19 genes within the ALS4 interval and detected missense mutations (T3I, L389S, and R2136H) in the Senataxin gene (SETX). The SETX gene encodes a novel 302.8-kD protein. Although its function remains unknown, SETX contains a DNA/RNA helicase domain with strong homology to human RENT1 and IGHMBP2, two genes encoding proteins known to have roles in RNA processing. These observations of ALS4 suggest that mutations in SETX may cause neuronal degeneration through dysfunction of the helicase activity or other steps in RNA processing.

Adolescent↗
PubMed2004

Clinical and genetic description of a family with Charcot-Marie-Tooth disease type 1B from a transmembrane MPZ mutation.

Mutations in the myelin protein zero gene (MPZ) are associated with certain demyelinating neuropathies, and in particular with Charcot-Marie-Tooth disease type 1B (CMT1B), Dejerine-Sottas syndrome, and congenital hypomyelination. MPZ mutations affecting the protein's transmembrane domain are generally associated with more severe phenotypes. We describe a family with mild CMT1B associated with a transmembrane MPZ mutation. Sequence analysis identified a G-to-C transversion at nucleotide 1064, predicting a glycine-to-arginine substitution in codon 163 (G163R) of MPZ. This report furthers the understanding of the clinical and electrophysiological manifestations of MPZ mutations.

Charcot-Marie-Tooth Disease↗
PubMed2002

Worsening of multifocal motor neuropathy during pregnancy.

Three women with multifocal motor neuropathy (MMN) were treated during pregnancy. Compared with their pregestation strength, the women became weaker in previously involved muscles and showed new weakness in previously unaffected muscles. All were treated with IV immunoglobulin during pregnancy and improved in strength. After pregnancy, strength in all patients returned to the prepregnancy state. The authors conclude that pregnancy may worsen MMN.

Adult↗