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Biomedical subjects

Allan H Ropper

Publications and source records attributed to Allan H Ropper.

At least 19 recordsLinked to original sources
PubMed2007

Rituximab treatment in patients with IVIg-dependent immune polyneuropathy: a prospective pilot trial.

We studied the effect of rituximab in allowing a reduction in dose of intravenous immune globulin (IVIg) in six patients with IVIg-dependent, relapsing immune polyneuropathy. Rituximab (375 mg/m(2) intravenously each week for 4 weeks) was administered in a prospective, open-label design to two patients with chronic inflammatory demyelinating polyneuropathy (CIDP), two with multifocal motor neuropathy (MMN), one with neuropathy and anti-myelin-associated glycoprotein (MAG) antibody neuropathy, and one with Sjögren syndrome (SS) ataxic neuropathy. The primary endpoint was a reduced cumulative IVIg dosage by at least 25% at 1 year after rituximab therapy compared to the previous year. Secondary endpoints included an improved summed strength score by at least 5 points on the Medical Research Council scale, an increased sensory score by at least 4 points, or an improved Rankin disability score by at least 1 grade. Total IVIg dosage decreased by greater than 25% in one patient with SS neuropathy and one with MMN; the dosage was unchanged in one with CIDP, slightly reduced in the patient with anti-MAG neuropathy, and increased in one with CIDP and another with MMN. There was no improvement in secondary endpoints. No adverse events occurred. In this small prospective study, rituximab did not reduce IVIg requirements in the majority of patients with IVIg-dependent, immune-mediated polyneuropathies.

Antibodies, Monoclonal↗
PubMed2007

Therapeutic angiogenesis inhibits or rescues chemotherapy-induced peripheral neuropathy: taxol- and thalidomide-induced injury of vasa nervorum is ameliorated by VEGF.

Toxic neuropathy represents an important clinical problem in the use of the chemotherapeutic substances Taxol and thalidomide. Sensory neuropathy has a high incidence, lacks an effective treatment and is the dose-limiting factor for these drugs. The pathogenic basis of these neuropathies is unknown. We investigated the hypothesis that the experimental toxic neuropathies from Taxol and thalidomide results from destruction of vasa nervorum and can be reversed by the administration of an angiogenic cytokine. In animal models of Taxol- and thalidomide-induced neuropathy, nerve blood flow has been attenuated and the number of vasa nervorum has been reduced. Intramuscular gene transfer of naked plasmid DNA encoding VEGF-1 administered in parallel with Taxol injections completely inhibited deterioration of nerve function and diminution of the peripheral nerve vasculature. Gene therapy in animals with established Taxol- or thalidomide-induced neuropathies resulted in recovery of vascularity and improved nerve electrophysiology. These findings implicate microvascular damage as the basis for toxic neuropathy and suggest that angiogenic growth factors may constitute a novel treatment for this disorder.

Animals↗
PubMed2006

The acute phase reactant, fibrinogen, as a guide to plasma exchange therapy for acute Guillain-Barré syndrome.

The Guillian Barré syndrome is an acute inflammatory disorder for which plasma exchange is effective treatment. Up to 10% relapse after plasma exchange suggesting that treatment sometimes finishes before disease activity has resolved. We studied whether plasma fibrinogen, an inflammatory marker, might be used to determine when to discontinue plasma exchange in patients with acute Guillain-Barré syndrome. We conducted a post-hoc analysis of apheresis database and hospital records of patients treated with plasma exchange for acute Guillain-Barré syndrome during 1999-2004. Data were analyzed from 28 patients who underwent a total of 29 courses of plasma exchange for acute Guillain-Barré syndrome. The mean (+/-SD) plasma fibrinogen concentration was 422.5 (+/-96.4) mg/dl at the time of presentation and, in 17 of the 29, it was above 400 mg/dl (reference range 200-400). Twenty of the 21 patients whose fibrinogen fell by more than 30% from baseline by the time of the final plasma exchange treatment had neurological improvement. There was improvement in only 3 of the 8 instances where fibrinogen decreased by less than 30% by the end of plasma exchange therapy. A > or =30% decrease in fibrinogen by the conclusion of plasma exchange was significantly associated with sustained neurological improvement (P = 0.0025). The plasma fibrinogen level appears to reflect disease activity in acute Guillain-Barré syndrome. A <30% fall in fibrinogen level despite plasma exchange may indicate the need to continue plasma exchange to maximize the benefit of treatment or minimize the risk of relapse. Therapeutic plasma exchange need not be extended when plasma fibrinogen remains > or =30% below its level at presentation by the time of the final planned plasma exchange procedure.

Acute Disease↗
PubMed2005

Antiangiogenesis mediates cisplatin-induced peripheral neuropathy: attenuation or reversal by local vascular endothelial growth factor gene therapy without augmenting tumor growth.

BACKGROUND: Toxic neuropathies induced by cisplatin and other chemotherapeutic agents are important clinical problems because of their high incidence, their lack of effective treatment, and the fact that neuropathy represents a dose-limiting factor for these therapies. The pathogenic basis for toxic neuropathies induced by chemotherapeutic agents has not been completely elucidated. METHODS AND RESULTS: We investigated the hypothesis that experimental toxic neuropathy results from an antiangiogenic effect of these drugs, resulting in destruction of the vasa nervorum, and accordingly that the neuropathy could be prevented or reversed by locally administered VEGF gene transfer without augmenting tumor growth. In an animal model of cisplatin-induced neuropathy, nerve blood flow was markedly attenuated, and there was a profound reduction in the number of vasa nervorum associated with marked endothelial cell apoptosis, resulting in a severe peripheral neuropathy with focal axonal degeneration characteristic of ischemic neuropathy. After intramuscular gene transfer of naked plasmid DNA encoding VEGF-1 in animals with an established neuropathy, vascularity and blood flow returned to levels similar to those of control rats, peripheral nerve function was restored, and histological nerve architecture was normalized. Gene therapy administered in parallel with cisplatin chemotherapy completely attenuated endothelial cell apoptosis and inhibited destruction of nerve vasculature, deterioration of nerve function, and axonal degeneration. In a rat tumor model, VEGF gene transfer administered locally did not alter tumor growth or vascularity. CONCLUSIONS: These findings implicate microvascular damage as the basis for toxic neuropathy induced by cisplatin and suggest that local angiogenic gene therapy may constitute a novel prevention or treatment for this disorder without augmenting tumor growth or vascularization.

Angiogenesis Inhibitors↗
PubMed2004

Efficacy of mycophenolate mofetil in patients with chronic immune demyelinating polyneuropathy.

The authors retrospectively reviewed the efficacy of mycophenolate mofetil (MMF; mean dose, 2 g/day given for an average of 14 months) in 21 patients with immune demyelinating polyneuropathy. There were no significant differences in the median strength, sensory, or Rankin scores before and after treatment. In patients with immunoglobulin (Ig) M neuropathy, the M-protein decreased by 22%. Three patients with chronic inflammatory demyelinating polyneuropathy (30%) and one patient with IgM neuropathy (13%) improved. The authors found that MMF induced a modest benefit in ~20% of their patients and stabilized patient condition, allowing reduction of steroid or IVIg therapy.

Adrenal Cortex Hormones↗
PubMed2004

The neuropeptide secretoneurin acts as a direct angiogenic cytokine in vitro and in vivo.

BACKGROUND: Secretoneurin is an abundant neuropeptide of the central, peripheral, and autonomic nervous systems, located in nerve fibers characterized by a close interaction with blood vessels and known to stimulate endothelial cell migration. METHODS AND RESULTS: We hypothesized that secretoneurin might act as an angiogenic cytokine and tested for these effects in vivo using a mouse cornea neovascularization model and in vitro by assessing capillary tube formation in a matrigel assay. In vivo, secretoneurin-induced neovasculature is characterized by a distinct pattern of arterial and venous vessels of large diameter and length. Immunohistochemical staining for CD-31 revealed endothelial lining of the inner surface of these vessels, and recruitment of alpha-smooth muscle actin-positive perivascular cells suggests vessel maturation. In vitro, secretoneurin-induced capillary tube formation was dose dependent and specific, confirming that effects of secretoneurin occur directly on endothelial cells. Secretoneurin also stimulated proliferation and exerted antiapoptotic effects on endothelial cells and activated intracellular phosphatidylinositol 3' kinase/Akt and mitogen-activated protein kinase pathways, as demonstrated by increased phosphorylation of Akt and extracellular signal-regulated kinase. CONCLUSIONS: These data show that secretoneurin represents a novel direct angiogenic cytokine and reiterate the coordinated relationship between nervous and vascular systems.

Angiogenesis Inducing Agents↗
PubMed2004

Barbiturate withdrawal following Internet purchase of Fioricet.

BACKGROUND: The Internet enables businesses to advertise their pharmaceutical products and services without medical supervision. The Internet also allows for the unsupervised purchase of medications that may have neurologic consequences. OBJECTIVE: To describe acute withdrawal delirium following the abrupt discontinuation of Fioricet. PATIENT: The patient was a 37-year-old woman with a history of depression and migraine headaches but not drug abuse. She developed a florid withdrawal delirium following the discontinuation of a drug she purchased online. The medication, which contained butalbital, was self-administered in escalating doses for the treatment of chronic headaches. Daily doses of up to 750 mg to 1000 mg were reported. RESULTS: The patient was admitted to the hospital for the treatment of unexplained seizures that were followed by several days of an intense withdrawal syndrome. Little improvement was noted after the administration of benzodiazepines and phenothiazine. After parenteral phenobarbital administration, her symptoms resolved. CONCLUSIONS: The withdrawal state from barbiturates is similar to that from ethanol. Tolerance can develop with prolonged abuse, leading to escalating drug doses to achieve the desired effect. The suggested management of both types of withdrawal syndromes is similar, but the relative resistance of the behavioral and autonomic features in patients was remarkable. Physicians should be aware of the ease with which medications can be purchased without supervision from Internet pharmacies. The magnitude of the number of drugs that are made available through this means creates a proclivity to withdrawal states.

Acetaminophen↗
PubMed2003

Current treatments for CIDP.

This article reviews the efficacy and tolerability of currently available therapies, including intravenous immunoglobulin (IVIg), corticosteroids, and plasma exchange (PE), for treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Data show that current therapies are effective in approximately two-thirds of patients. However, they fail to provide a durable clinical response. Furthermore, current treatments have several limitations that make them problematic for long-term therapy. IVIg dosing is required approximately every 2 to 8 weeks in most patients to maintain improvement. It is expensive, time-consuming to administer, and availability can be a problem. Furthermore, IVIg is a blood product that is associated with rare thromboembolic events. Corticosteroids have poor safety and tolerability profiles, and PE is invasive, time-consuming, expensive, and can be performed only at specialized centers. An alternative to single-agent therapy with current treatments is the use of combination therapy. Combination therapy may increase the duration of response, provide increased efficacy or independent efficacy in unresponsive patients, and reduce the need for standard therapies. Research is needed to find agents suitable for single and combination therapy in CIDP.

Adrenal Cortex Hormones↗
PubMed2003

Symmetric deep cerebellar lesions after smoking heroin.

BACKGROUND: Acute symmetric deep cerebellar lesions suggest toxic exposure. OBJECTIVE: To describe a patient with striking neurologic and magnetic resonance image features. DESIGN: Case report. SETTING: Emergency department and office. METHODS: Personal observation. RESULTS: A middle-aged man had a day of unsteadiness, followed by acute and pronounced cerebellar signs. The degree of disability was remarkable. Magnetic resonance imaging showed almost perfectly symmetric deep cerebellar damage that ultimately became cavitated. Serial querying of the patient revealed the use of heroin by inhalation just prior to the emergence of the ataxic syndrome. CONCLUSIONS: An acute and purely ataxic syndrome with symmetric deep cerebellar lesions suggests toxic exposure, in this case, the smoking of heroin.

Administration, Inhalation↗
PubMed2003

Vasculitis of the spinal cord.

BACKGROUND: Vasculitis of the central nervous system is rare but well described. It affects the cerebral hemispheres predominantly and only exceptionally involves the spinal cord. OBJECTIVE: To describe a case of spinal cord vasculitis with unusual pathologic changes. DESIGN: Case report with clinicopathologic correlation. Case Description A young man developed leg weakness and sensory symptoms over several weeks. He had an asymmetric paraparesis with impaired vibration sense in the feet and a Romberg sign but no sensory level. The cerebrospinal fluid contained 123 white blood cells x103/ micro L, mostly lymphocytes, and a protein concentration of 52 mg/dL; oligoclonal bands were not detected, but the illness simulated multiple sclerosis. Magnetic resonance imaging scans of the spinal cord and brain were normal. His condition improved on several occasions with intravenous infusions of corticosteroid agents, but his neurologic signs gradually worsened over several months, and he acquired a thoracic sensory level and sphincteric abnormalities. An explosive preterminal illness occurred with paraplegia, nystagmus, and coma. The findings of a pathologic examination showed numerous ischemic areas in the spinal cord, some cavitated, and a vasculitis of the leptomeningeal branches of the anterior spinal artery and of subpial vessels. The vessel walls were not necrotic, but many of their lumens were occluded by fibrinous material. There were similar findings in regions of cerebral hemorrhagic infarction. CONCLUSIONS: A destructive and vasculitic process should be considered in cases of subacute myelopathy with persistent cellular reaction in the cerebrospinal fluid and clinical responsiveness to corticosteroid therapy. The magnetic resonance imaging scan of the spinal cord may be normal.

Adult↗
PubMed2003

Positive salivary gland biopsy, Sjögren syndrome, and neuropathy: clinical implications.

The relationship between neuropathy and Sjögren syndrome has been predicated largely on sicca symptoms or serological abnormalities rather than salivary gland pathology. We reviewed consecutive neuropathy patients who had had a lip biopsy to identify features of the neuropathy that were associated with a positive lip biopsy suggesting Sjögren syndrome. Twenty of 54 neuropathy patients were biopsy positive; 13 had a painful or nonspecific sensory neuropathy and only 4 were ataxic. Sicca symptoms were not associated with a positive biopsy (P = 0.14). Serological abnormalities were found more often in the biopsy-positive group (P = 0.008), but anti-Sjögren syndrome A or B (anti-SSA or SSB) antibodies were detected in only 30%. There were no other clinical or electromyographic (EMG) features associated with a positive biopsy. From this experience, we conclude that: (1). most patients with neuropathy and a positive lip biopsy for Sjögren syndrome have a painful, distal, sensory axonal neuropathy; (2). there are no clinical or EMG features that are predictive of a positive lip biopsy; (3). ataxic neuropathy is uncommon; and (4). the lack of sicca symptoms or anti-SSA or SSB antibodies in patients with neuropathy does not exclude Sjögren syndrome based upon salivary gland pathology.

Adult↗
PubMed2002

Familial Kleine-Levin syndrome: two siblings with unusually long hypersomnic spells.

Kleine-Levin syndrome is a rare, sporadic disorder, with discrete spells of hypersomnolence occurring during adolescence, variously accompanied by megaphagia, behavioral changes, psychosis, and mild autonomic symptoms. Familial cases have not previously been reported. We describe 2 siblings who shared uncharacteristically prolonged episodes of hypersomnolence, and the HLA-DR2 haplotype. In one patient, levels of cerebrospinal fluid orexin (hypocretin) during an attack were normal. The presence of an increased sleep drive, despite the occurrence of large amounts of ostensibly restorative sleep, suggests the possible existence of a disorder of sleep satiety.

Adolescent↗