The additional yield of combined nerve/muscle biopsy in vasculitic neuropathy.

BACKGROUND: vasculitic neuropathy can be confirmed by demonstrating vasculitis in a nerve biopsy, but it is uncertain to what extent combined (i.e. nerve/muscle) biopsy improves the yield. METHODS: a random-effects meta-analysis was performed to assess the additional yield of combined biopsy in vasculitic neuropathy. Medline, Embase, LILACS and ISI were searched from January 1980 until January 2009 for relevant articles on the yield of nerve, muscle or combined biopsy to diagnose vasculitic neuropathy. Fourteen (15%) studies were included. Methodological quality was scored using a modified Quality Assessment for Diagnostic Accuracy Studies tool. RESULTS: in patients clinically suspected of vasculitic neuropathy, the additional yield of definite vasculitis in combined biopsy was 5.1% (95% CI 1.1-9.2%; P = 0.013). In patients diagnosed with vasculitic neuropathy, the additional yield of definite vasculitis in combined biopsy was 15% (95% CI 2.1-28%; P = 0.023). CONCLUSIONS: there is a modest additional yield of definite vasculitis in combined biopsy compared to nerve biopsy alone. Because of methodological flaws in analysed studies, the findings should be validated in a prospective study.

Isolated vasculitis of the peripheral nervous system.

Vasculitis restricted to the peripheral nervous system (PNS), referred to as nonsystemic vasculitic neuropathy (NSVN), has been described in many reports since 1985 but remains a poorly understood and perhaps under-recognized condition. There are no uniform diagnostic criteria. Classification is complicated by the occurrence of vasculitic neuropathies in many systemic vasculitides affecting small-to-medium-sized vessels and such clinical variants as nonsystemic skin/nerve vasculitis and diabetic/non-diabetic lumbosacral radiculoplexus neuropathy. Most patients present with painful, stepwise progressive, distal-predominant, asymmetric or multifocal, sensory-motor deficits evolving over months-to-years. NSVN is identical to but less severe than systemic vasculitis-associated neuropathies (SVNs). All vasculitic neuropathies are axonal by electrodiagnostic/pathologic criteria. Laboratory testing is unremarkable except for mildly elevated erythrocyte sedimentation rate (ESR) in 50%. Highly elevated ESRs, leukocytosis, rheumatoid factors, and anti-neutrophil cytoplasmic antibodies (ANCAs) raise concern for underlying systemic vasculitis. Without a specific clinical/laboratory marker, the condition depends on nerve biopsy for diagnosis. Biopsies showing necrotizing vasculitis are about 50% sensitive, mandating reliance on "suspicious" changes in many patients. Vasculitic lesions predominate in smaller epineurial vessels and are milder than those in SVNs. The disorder is often accompanied by subclinical involvement of adjacent muscles and skin. NSVN has the potential to spontaneously relapse and remit but neurologic deficits accumulate. No randomized controlled trials have been performed, but one retrospective cohort survey showed combination therapy to be more effective than prednisone alone. Although most patients have a good outcome, more than 30% relapse and 60% have residual pain. Many nosologic, pathogenic, diagnostic, and therapeutic questions remain unanswered.

Nonsystemic vasculitic neuropathy: insights from a clinical cohort.

BACKGROUND: Nonsystemic vasculitic neuropathy (NSVN) is an uncommon disorder. Few series with small numbers of patients have been reported. The prognosis and treatment of patients presenting with NSVN remain uninvestigated. The authors sought to address these issues by assembling a large retrospective cohort with extended follow-up. METHODS: All nerve biopsies performed over 20 years were reviewed; cases with definite, probable, or possible vasculitis were segregated for clinical correlation. Patients satisfying clinical criteria for NSVN at presentation were selected. Clinicopathologic, treatment, and outcome measures were analyzed in patients followed for > or = 6 months. RESULTS: A total of 48 patients (30 women, 18 men) with a median of 63 months of follow-up were identified. Most patients (85%) had extensive, overlapping involvement of multiple nerves. Only one had a symmetric polyneuropathy. Most neuropathies (96%) were painful. In 96%, nerve damage was distally accentuated, but most had concurrent proximal weakness. Diagnostic sensitivity was 58% for superficial peroneal nerve/peroneus brevis muscle biopsy and 47% for sural nerve biopsy. Combination corticosteroid/cytotoxic therapy was more effective than corticosteroid monotherapy in inducing remission and improving disability, with trends toward reduced relapses and chronic pain. Treatment with cyclophosphamide for >6 months decreased the relapse rate, which was 46% for all patients. Disease/treatment-related mortality was 10%. Six percent developed cutaneous involvement. Although chronic pain persisted in 60% of survivors, 80% had good outcomes. CONCLUSIONS: NSVN nearly always presents as an asymmetric, distally accentuated, painful, sensorimotor polyneuropathy. Risks for systemic spread and death are small, and, aside from pain, neurologic prognosis is unexpectedly good. Although this was not a randomized controlled trial, combination therapy produced the best outcome in this cohort.

Hypocapnia and other ventilation-related risk factors for cerebral palsy in low birth weight infants.

Ventilatory management patterns in very low birth weight newborns, particularly iatrogenic hypocapnia, have occasionally been implicated in perinatal brain damage. However, such relationships have not been explored in large representative populations. To examine the risk of disabling cerebral palsy in mechanically ventilated very low birth weight infants in relation to hypocapnia and other ventilation-related variables, we conducted a population-based prospective cohort study of 1105 newborns with birth weights of 500-2000 g born in New Jersey from mid-1984 through 1987, among whom 777 of 902 survivors (86%) had at least one neurodevelopmental assessment at age 2 y or older. Six hundred fifty-seven of 777 assessed survivors (85%), of whom 400 had been mechanically ventilated, had blood gases obtained during the neonatal period. Hypocapnia was defined as the highest quintile of cumulative exposure to arterial PCO(2) levels <35 mm Hg during the neonatal period. Disabling cerebral palsy was diagnosed in six of 257 unventilated newborns (2.3%), 30 of 320 ventilated newborns without hypocapnia (9.4%), and 22 of 80 ventilated newborns with hypocapnia (27.5%). Two additional ventilatory risk factors for disabling cerebral palsy were found-hyperoxia and prolonged duration of ventilation. In a multivariate analysis, each of the three ventilatory variables independently contributed a 2- to 3-fold increase in risk of disabling cerebral palsy. These risks were additive. Although duration of mechanical ventilation in very low birth weight newborns likely represents severity of illness, both hypocapnia and hyperoxia are largely controlled by ventilatory practice. Avoidance of arterial PCO(2) levels <35 mm Hg and arterial PO(2) levels >60 mm Hg in mechanically ventilated very low birth weight infants would seem prudent.

Randomized trial of amplification strategies.

BACKGROUND: Little is known about quality of life after the use of specific types of hearing aids, so it is difficult to determine whether technologies such as programmable circuits and directional microphones are worth the added expense. OBJECTIVE: To compare the effectiveness of an assistive listening device, a nonprogrammable nondirectional microphone hearing aid, with that of a programmable directional microphone hearing aid against the absence of amplification. DESIGN: Randomized controlled trial. SETTING: Audiology clinic at the VA Puget Sound Health Care System, Seattle, Wash. PATIENTS: Sixty veterans with bilateral moderate to severe sensorineural hearing loss completed the trial. Half the veterans (n = 30) had hearing loss that the Veterans Affairs clinic determined was rated as "service connected," which meant that they were eligible for Veterans Affairs-issued hearing aids. INTERVENTION: Veterans with non-service-connected hearing loss, who were ineligible for Veterans Affairs-issued hearing aids, were randomly assigned to no amplification (control arm) or to receive an assistive listening device. Veterans with service-connected loss were randomly assigned to receive either the nonprogrammable hearing aid that is routinely issued ("conventional") or a programmable aid with a directional microphone ("programmable"). MAIN OUTCOME MEASURES: Hearing-related quality of life, self-rated communication ability, adherence to use, and willingness to pay for the amplification devices (measured 3 months after fitting). RESULTS: Clear distinctions were observed between all 4 arms. The mean improvement in hearing-related quality of life (Hearing Handicap Inventory for the Elderly) scores was small for control patients (2.2 points) and patients who received an assistive listening device (4.4 points), excellent for patients who received a conventional device (17.4 points), and substantial for patients who received a programmable device (31.1 points) (P<.001 by the analysis of variance test). Qualitative analyses of free-text diary entries, self-reported communication ability (Abbreviated Profile of Hearing Aid Benefit) scores, adherence to hearing aid use, and willingness to pay for replacement devices showed similar trends. CONCLUSIONS: A programmable hearing aid with a directional microphone had the highest level of effectiveness in the veteran population. A nonprogrammable hearing aid with an omnidirectional microphone was also effective compared with an assistive listening device or no amplification.

Autonomic impairment in painful neuropathy.

OBJECTIVES: 1) To determine the degree and distribution and quantitate the severity of autonomic impairment in painful neuropathy (PN). 2) To assess the role of autonomic testing in evaluating PN. METHODS: The authors studied 92 patients with PN (60 women and 32 men, age 56.9 +/- 12.4 years) using: 1) autonomic reflex testing (ART), Quantitative Sudomotor Axon Reflex Test (QSART), cardiac-vagal, head-up tilt, and surface skin temperature; 2) autonomic symptoms questionnaire; 3) nerve conduction (NCS) and laboratory studies; 4) quantitative sensory testing; 5) skin biopsy; and 6) Composite Autonomic Symptoms Score (CASS) scale to grade ART results from 0 (normal) to 10 (autonomic failure). RESULTS: Autonomic involvement in PN had characteristic features. Main symptoms were pain, secretory and skin vasomotor signs, hypertension, and impotence. ART results were abnormal in 86 (93.5%) (CASS < 4), QSART in 67 (72.8%), cardiac-vagal index in 58 (63%), skin temperature in 51 (55.4%), orthostatic hypertension in 39 (42.3%), and family history of PN in 26 (21%) of patients. Group 1 (abnormal NCS) (n = 45) had more severe ART and sensory abnormalities than the Group 2 (normal NCS) (n = 47): 1) CASS 2.0 +/- 0.96 vs 1.55 +/- 0.88 (p < 0.01), cardiac-vagal index (p < 0.02), skin temperature (p < 0.02), hypertension (p < 0.03), cooling (p < 0.002), and vibration (p < 0.0005) thresholds. CONCLUSIONS: Autonomic symptoms in painful neuropathy are predominantly cholinergic and form a unique constellation of features that are distinct from other autonomic neuropathies.

Application of acoustic emission to the monitoring and end point determination of a high shear granulation process.

The application of a novel monitoring technique, based on the use of acoustic emissions, is reported for a model high shear granulation process. It has been demonstrated that this technique is capable of monitoring changes in physical properties of powder material during granulation (particle size, flow properties and compression properties). The technique is non-invasive, sensitive and relatively inexpensive.

Superficial peroneal nerve/peroneus brevis muscle biopsy in vasculitic neuropathy.

OBJECTIVE: To determine the sensitivity and specificity of superficial peroneal nerve (SPN)/peroneus brevis muscle (PBM) biopsy in a cohort of patients with suspected peripheral nerve vasculitis. BACKGROUND: In patients with suspected vasculitic neuropathy, combined nerve and muscle biopsies have been advocated as a way to increase the diagnostic yield, but the sensitivity and specificity of this approach have not been evaluated. Pathologic predictors of biopsy-proven peripheral nerve vasculitis have also not been analyzed in a systematic fashion. METHODS: The clinical, laboratory, and pathologic data for all patients undergoing SPN/PBM biopsy for possible vasculitis from 1986 through 1996 were analyzed. Biopsies were classified as positive, negative, or suspicious for vasculitis. Patients were then divided into vasculitis and nonvasculitis cohorts by final clinical diagnosis. RESULTS: Of 70 SPN/PBM biopsies, 22 (30%) showed definite vasculitis; nerve was diagnostic in 90% (n = 20) and muscle in 50% (n = 11). Nerve biopsy had a higher yield than muscle in patients with nonsystemic vasculitic neuropathy (p = 0. 0047) but not in those with systemic vasculitis. The estimated sensitivity of a positive SPN/PBM biopsy for vasculitis was 60%. Considering biopsies either positive or suspicious for vasculitis increased the sensitivity to 86% with a corresponding specificity of 85%. Pathologic features associated with necrotizing vasculitis were muscle fiber necrosis/regeneration (relative risk 18.1; 95% CI 3.4 to 96.1), predominant axonal nerve pathology (>8.8; >1.0 to 77.4), Wallerian-like degeneration (5.6; 1.4 to 21.9), and asymmetric nerve fiber loss (4.6; 1.4 to 15.9). CONCLUSIONS: These findings establish the yield, sensitivity, and specificity of SPN/PBM biopsy for diagnosing vasculitic neuropathy and validate the use of suggestive pathologic features for diagnosing cases lacking definite necrotizing vascular changes.

Painful sensory neuropathy: prospective evaluation using skin biopsy.

OBJECTIVE: In patients presenting with painful, burning feet with minimal signs of neuropathy, the following questions were addressed: 1) How many of these patients have a peripheral neuropathy? 2) What is the role of skin biopsy in establishing a diagnosis of neuropathy? 3) What conditions are associated with the neuropathy? and 4) What laboratory studies are useful in this patient population? METHODS: A total of 117 consecutive patients referred for evaluation were prospectively studied. All underwent nerve conduction studies (NCS) and a battery of blood tests, including antinerve antibodies. If NCS were normal, a punch biopsy of the skin of the distal leg was performed to ascertain the intraepidermal nerve fiber (IENF) density. In a subset of 32 patients, the sensitivity of skin biopsy was compared to quantitative sudomotor axon test (QSART) and quantitative sensory tests (QST). RESULTS: Three groups emerged. Group 1, with abnormal NCS (n = 60, 34 F/26 M, mean age 60 +/- 14 years), represented 51% of the cohort. The majority had neuropathies of undetermined cause, but 18 (30%) had associated conditions. Group 2, with normal NCS and reduced IENF density (n = 44, 29 F/15 M, mean age 57 +/- 14 years), represented 38% of the cohort. Three in this group had associated conditions. Group 3, with normal NCS and IENF density (n = 13, 6 F/7 M, mean age 53 +/- 13 years), represented 11% of the cohort; most had no diagnoses but two had MS. In a comparative subset analysis, skin biopsy was more sensitive than QSART or QST in diagnosing a neuropathy. CONCLUSIONS: Patients presenting with painful feet are heterogeneous, consisting of both large and small fiber sensory neuropathies. In rare cases, a central cause for pain can be found. Over one-third of patients required a skin biopsy to diagnose a small fiber sensory neuropathy. A limited battery of blood tests facilitated diagnosis, but serum antinerve antibodies were not helpful.

Neuropathies associated with malignancy.

Patients with malignancy can develop peripheral neuropathies as (1) a direct effect of the cancer by invasion or compression of nerves, (2) a remote or paraneoplastic effect, or (3) an iatrogenic effect of treatment. Focal or multifocal cranial neuropathies, radiculopathies, and plexopathies typically result from tumor infiltration, herpes zoster infection, or radiation-induced injury. Sensorimotor polyneuropathies are the most frequently encountered peripheral nerve syndromes, but motor neuropathies, sensory neuronopathies, polyradiculoneuropathies, and autonomic neuropathies can also occur. Although uncommon, paraneoplastic mechanisms should be considered in a patient with malignancy and an associated peripheral nerve disorder, especially in the setting of small-cell lung cancer or lymphoproliferative cancer. Toxic neuropathies occur with exposure to several chemotherapeutic agents, including the vinca alkaloids, cisplatin, taxanes, and suramin. These neuropathies are usually dose-related, sensory-predominant, and at least partially reversible, with an axonopathic or ganglionopathic mechanism. Suramin is unique in causing subacute, demyelinating polyradiculoneuropathy.

Traumatic rupture of the pulmonary artery.

Traumatic rupture of the main pulmonary artery in a surviving patient is very rare. The case history of a 37-year-old man who sustained blunt chest trauma in a motor vehicle accident is presented. A persistent, bloody right pleural effusion led to the diagnosis of a ruptured right main pulmonary artery, which was surgically repaired using cardiopulmonary bypass. Points of diagnostic interest and therapeutic decision making are discussed.

Management of refractory empyema with early decortication.

One hundred consecutive patients underwent surgical procedures for empyema. Sixty-six patient acquired empyema from pneumonia, 16 from trauma, 11 from abdominal sepsis, and 7 from other causes. If tube thoracostomy failed, computerized tomography and ultrasonography were used to demonstrate a loculated empyema. After a median observation period of 11 days, 91 patients underwent thoracotomy and decortication and 9 patients underwent either rib resection, an Eloesser flap procedure, or both. The mortality rate was 6 percent 30 days postoperatively, the in-hospital mortality rate was 9 percent, and the overall morbidity rate was 17 percent. An excellent result was achieved in 85 percent of the patients with a recurrence rate of 4 percent. Gram-positive aerobes were the most common organisms cultured, but several opportunistic infections were encountered. We have concluded that early thoracotomy and decortication of empyema results in eradication of difficult pleural infections with hospital stays of an acceptable length and reasonably low morbidity and mortality rates.

Sporothrix schenckii endophthalmitis in a patient with human immunodeficiency virus infection.

A 30-year-old homosexual man with a positive serologic test for human immunodeficiency virus and a history of successfully treated disseminated cutaneous sporotrichosis developed a granulomatous uveitis that worsened with topical and subconjunctival steroid therapy. Culture of the aqueous aspirate yielded Sporothrix schenckii. The patient was treated with intravenous amphotericin B and intravitreal amphotericin B, kanamycin sulfate, and amikacin sulfate. Subsequent aqueous and vitreous cultures were negative, but the intraocular inflammatory process progressed and ultimately led to enucleation of the eye. Histopathologic examination revealed granulomatous inflammation of the anterior uvea and scattered S schenckii in the anterior and posterior chambers. Electron microscopy demonstrated that most of the organisms had disorganized protoplasm. Although treatment failed to ameliorate the progressive intraocular inflammatory process, the negative cultures and the electron microscopic observations suggest that the treatment was reasonably effective in killing S schenckii within the eye. To our knowledge, this is the first case report of S schenckii endophthalmitis in a patient with human immunodeficiency virus infection.

Adenoid histamine and its possible relationship to secretory otitis media.

We have shown that adenoid tissue contains large amounts of the inflammatory mediator histamine. Children with fluid present in both ears at operation were found to have increased amounts of histamine in their adenoid tissue compared to a group with no signs or symptoms of SOM. Also mouth breathing and nasal obstruction were associated with adenoid histamine content whereas other signs and symptoms were not. No significant differences in adenoid weight were seen between SOM and non SOM patients. Histamine, both free and cell-associated, was found in nasopharyngeal secretions and middle-ear fluid although the source and mechanism of release has not yet been identified. We suggest that the benefits of adenoidectomy in children with SOM may possibly come from removing a potential source of inflammatory mediators in the vicinity of the Eustachian tube.

A practical guide to the construction of a "cire perdue" model of the human nose.

A step by step method of constructing a model of the human nose is described. The hollow model faithfully reproduces the main features of the internal structure of the nasal air passages and nasopharynx. A model constructed by this technique was found to be suitable for nasopharyngeal airflow studies.

Histamine and secretory otitis media.

Histamine, both free and cell associated, has been demonstrated in middle ear fluid from patients with secretory otitis media (SOM). Histamine, mainly free in solution, has also been shown to be present in nasopharyngeal secretions taken from close to the Eustachian tube openings into the nasopharynx. The adenoids from patients with middle ear effusion contained significantly (P less than 0.05) more histamine than those with no effusion. However, in preliminary experiments, we could demonstrate no differences in the histamine secretory response of adenoids from SOM and non-SOM patients to anti-immunoglobulin E (anti-IgE), house dust mite antigen and calcium inophore A23187 in vitro. These results support the hypothesis of an inflammatory basis for SOM.