Clinical practice. Concussion.
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Amnesia, Retrograde↗
Biomedical subjects
Kenneth C Gorson
Publications and source records attributed to Kenneth C Gorson.
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↗
Vasculitic neuropathies: an update.
BACKGROUND: Systemic vasculitis has been classically categorized as a primary disorder, such as polyarteritis nodosa, Churg-Strauss syndrome, and Wegener granulomatous, or as a secondary process, representing a complication from a connective tissue disorder (eg, rheumatoid vasculitis), infection, medication, or malignancy. Peripheral neuropathy is a well-recognized consequence of systemic vasculitis due to peripheral nerve infarction with Wallerian degeneration. Rarely, neuropathy is the sole manifestation of vasculitis, referred to as nonsystemic vasculitic neuropathy (NSVN). These conditions are defined pathologically by tissue biopsy demonstrating disruption or destruction of the vessel wall with inflammatory cell infiltrates. REVIEW SUMMARY: The diagnosis of vasculitic neuropathy is straightforward in patients with an established diagnosis of systemic vasculitis and classic features of mononeuritis multiplex. Most patients have clinical features of a subacute, progressive, generalized but asymmetric, painful, sensorimotor polyneuropathy. Laboratory tests often indicate features of systemic inflammation, such as an elevated sedimentation rate or positive anti-neutrophil cytoplasmic antibody, and electrodiagnostic evaluation shows multiple mononeuropathies or a confluent, asymmetric axonal neuropathy. Nerve biopsy is necessary to establish the diagnosis in most cases, particularly in patients with NSVN. This review summarizes the current treatment of vasculitic neuropathy. CONCLUSION: Long-term immunosuppressive therapy is required in most cases. High-dose prednisone combined with intravenous pulse or oral daily cyclophosphamide is standard initial therapy. In those with NSVN, cyclophosphamide also should be used if prednisone monotherapy is ineffective or the patient relapses with tapering. Other agents, such as azathioprine, methotrexate, intravenous immunoglobulin, mycophenolate mofetil, plasma exchange, and rituximab can be offered to patients who are intolerant or have a contraindication to cyclophosphamide. However, evidence for the benefit of these agents is limited to case reports and small case series.
Humans↗
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↗
Therapy for vasculitic neuropathies.
The term vasculitis refers to a pathologic condition defined by inflammatory cell infiltration and destruction of blood vessels. Systemic vasculitis is classified as primary (eg, polyarteritis nodosa, Churg-Strauss syndrome) or secondary, the latter associated with connective tissue disorders, infections, medications, and rarely, as a paraneoplastic phenomenon. Neuropathy is a common complication of systemic vasculitis and is related to ischemic nerve fiber damage with axon loss. Peripheral neuropathy may be the sole manifestation of vasculitis, a condition termed nonsystemic vasculitic neuropathy (NSVN). Treatment of vasculitic neuropathy requires long-term immunosuppressive therapies with potential side effects. The diagnosis of vasculitis should be established by tissue (preferably nerve) biopsy. High-dose prednisone is the standard platform therapy for patients with systemic and NSVN; for those with systemic vasculitis, at least 3 to 12 months of treatment with cyclophosphamide (monthly intravenous pulse or daily oral therapy) is also necessary to sustain remission and allow successful prednisone tapering. The use of cyclophosphamide in patients with NSVN is controversial, but recent retrospective data suggest that those treated with prednisone and cyclophosphamide from the outset fare better than those initially treated only with prednisone. If prednisone is administered as monotherapy, cyclophosphamide should be added after several months if there is no improvement or relapse occurs with tapering of prednisone. Intravenous pulse and daily oral cyclophosphamide probably offer similar efficacy, although the risk of complications is greater with oral therapy. Azathioprine can be safely substituted for cyclophosphamide after 3 months without an increased relapse rate. Azathioprine, methotrexate, intravenous immune globulin, mycophenolate mofetil, plasma exchange, and rituximab can be offered to patients who are intolerant or have a contraindication to cyclophosphamide. However, efficacy is unproven for any of these therapies. Interferon-alpha, sometimes combined with plasma exchange, is used to treat vasculitis associated with hepatitis B infection. Some patients also may improve with corticosteroids. The classification of diabetic lumbosacral radiculoplexus neuropathy as a vasculitic disorder remains controversial. However, there is compelling pathological evidence that this condition represents a T-cell-mediated microvasculitis. Some patients treated with intravenous corticosteroids may have greater recovery and improved pain control.
Journal Article↗
Approach to neuromuscular disorders in the intensive care unit.
Neuromuscular disorders increasingly are recognized as a complication in patients in the intensive care unit (ICU) and represent a common cause of prolonged ventilator dependency. The distinct syndromes of critical illness myopathy, prolonged neuromuscular blockade, and critical illness polyneuropathy (CIP) may arise as a consequence of sepsis, multi-organ failure, and exposure to various medications--notably, intravenous corticosteroids and neuromuscular blocking agents--but the pathophysiology of these disorders remains poorly understood. More than one syndrome may occur simultaneously, and the distinctions may be difficult in a particular patient, but a specific diagnosis usually can be established after careful clinical, electrodiagnostic, and, when necessary, histological evaluation. For example, asthmatics requiring treatment with corticosteroids and neuromuscular blocking agents may develop an acute myopathy characterized by generalized weakness, preserved eye movements, elevated creatine kinase levels, and myopathic motor units on electromyography (EMG). Muscle biopsy demonstrates distinctive features of thick (myosin) filament loss on ultrastructural studies. Conversely, those with a prolonged ICU course that is complicated by episodes of sepsis with failure to wean from the ventilator, distal or generalized flaccid limb weakness, and areflexia probably have CIP. EMG in these patients demonstrates reduced or absent motor and sensory potentials with neurogenic motor units. Prolonged neuromuscular blockade most commonly occurs in patients with renal failure who have received prolonged infusions of neuromuscular blockers. There is severe flaccid, areflexic paralysis with normal sensation, facial weakness, and ophthalmoparesis that persists for days or weeks after the neuromuscular blockers have been discontinued. Repetitive nerve stimulation shows a decrement of the compound muscle action potential and, in most cases, establishes a disorder of neuromuscular transmission. With the recent epidemic of West Nile virus infection, a clinical syndrome of acute flaccid paralysis with several features indistinguishable from poliomyelitis has emerged. This article critically examines the clinical, electrophysiological, and pathological features of these and other acute neuromuscular syndromes that arise in the context of ICU care and summarizes the current understanding of the pathophysiology and treatment of these disorders.
Critical Illness↗
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↗
The use of complementary and alternative medicines by patients with peripheral neuropathy.
Complementary and alternative medicine (CAM) therapies have become increasingly popular and are used regularly by patients with chronic neurological disorders. The prevalence and characteristics of CAM use by patients with peripheral neuropathy is unknown. We performed a prospective, questionnaire-based study to determine the prevalence and patterns of use of CAM therapies in 180 consecutive outpatients with peripheral neuropathy. The use of CAM was reported by 77 patients (43%) with neuropathy. The most frequent were megavitamins (35%), magnets (30%), acupuncture (30%), herbal remedies (22%), and chiropractic manipulation (21%); 37 (48%) tried more than one form of alternative treatment. Seventeen respondents (27%) thought their neuropathy symptoms improved with these approaches. Those who used CAM were slightly younger (mean age 62 vs. 65 years, p = 0.05) and more often college educated (39% vs. 24%, p = 0.03) compared to CAM nonusers. They also more often reported burning neuropathic pain (62% vs. 44%, p = 0.01). Patients with diabetic neuropathy used CAM more frequently than others (p = 0.03). The most common reason for using CAM was inadequate pain control (32%). Almost half of patients did not consult a physician before starting CAM. We conclude that there is a high prevalence of CAM use in our patients with neuropathy, and one-quarter reported that their symptoms improved. CAM users were better educated than nonusers, but most did not discuss CAM treatments with their physician. Neuropathic pain was substantially more common in CAM users, and lack of pain control was the most common reason for CAM use.
Acupuncture Therapy↗
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↗
Efficacy of intravenous immunoglobulin in patients with IgG monoclonal gammopathy and polyneuropathy.
CONTEXT: The optimal treatment of patients with neuropathy associated with IgG monoclonal gammopathy of undetermined significance is unknown. Plasma exchange has been shown to be effective but alternative therapies have not been systematically evaluated. OBJECTIVE: To report our experience with intravenous immunoglobulin (IVIG) in patients with IgG monoclonal gammopathy of undetermined significance polyneuropathy. DESIGN: Retrospective review of clinical and electrodiagnostic features of 20 consecutive patients treated with IVIG over an 8-year period. SETTING: Academic medical center. MAIN OUTCOME MEASURES: Medical Research Council strength (maximum, 40 points) and sensory (maximum, 26 points) scores, modified Rankin Disability Scale score. RESULTS: There were 14 men and 6 women (mean age, 65 years; age range, 36-82 years). The mean strength score was 35.6 points and the mean sensory score was 15.8 points prior to therapy. After IVIG therapy, the mean strength score increased by 1.1 points (P =.22) and the sensory score increased by 1.7 points (P =.11). Eight patients (40%) improved by 2 points or more in their motor or sensory score and 1 point or more in the modified Rankin Disability Scale score and were considered IVIG therapy responders. They had a shorter duration of symptoms (P =.03), numb hands (P =.02), and falling episodes (P =.02), and had greater proximal leg weakness (P =.02) compared with nonresponders. In IVIG therapy responders, the ulnar motor conduction velocity was slower, ulnar and peroneal distal motor latencies were prolonged, and the frequency of conduction block was higher (13 of 36 motor nerves in responders vs 6 of 53 in nonresponders, P =.008). CONCLUSIONS: Intravenous immunoglobulin therapy was beneficial in 8 (40%) of our 20 patients with polyneuropathy and IgG monoclonal gammopathy of undetermined significance. Proximal leg weakness, short duration of symptoms, and demyelinating features on electrodiagnostic studies were associated with a response to IVIG therapy.
Adult↗