Patient-reported outcomes with subcutaneous immunoglobulin in chronic inflammatory demyelinating polyneuropathy: the PATH study.

BACKGROUND AND PURPOSE: Chronic inflammatory demyelinating polyneuropathy (CIDP) causes weakness which adversely impacts function and quality of life (QOL). CIDP often requires long-term management with intravenous or subcutaneous immunoglobulin. The Polyneuropathy and Treatment with Hizentra® (PATH) study showed that subcutaneous immunoglobulin (SCIG) was efficacious in CIDP maintenance. Here, patient-reported outcomes in patients on SCIG are assessed. METHODS: Subjects stabilized on intravenous immunoglobulin were randomly allocated to receive weekly 0.2 or 0.4 g/kg bodyweight of 20% SCIG (IgPro20) or placebo. Overall QOL/health status was assessed using the EuroQoL 5-Dimension (EQ-5D) health profile and visual analog scale, treatment satisfaction was assessed with the Treatment Satisfaction Questionnaire for Medicine (TSQM) and work-related impact was assessed with the Work Productivity and Activity Impairment Questionnaire for General Health (WPAI-GH). The EQ-5D health profile was assessed in terms of the percentage of subjects maintained or improved at week 25 of SCIG therapy on each of the EQ-5D domains versus baseline after intravenous immunoglobulin stabilization. TSQM and WPAI-GH were assessed by median score changes from baseline to week 25. RESULTS: In total, 172 subjects were randomized to placebo (n = 57), 0.2 g/kg IgPro20 (n = 57) and 0.4 g/kg IgPro20 (n = 58). Significantly higher proportions of IgPro20-treated subjects improved/maintained their health status on the EQ-5D usual activities dimension, and in additional dimensions (mobility and pain/discomfort) in sensitivity analyses. TSQM and WPAI-GH scores were more stable with IgPro20 treatment compared with placebo. CONCLUSIONS: IgPro20 maintained or improved QOL in most subjects with CIDP, consistent with the PATH study findings that both IgPro20 doses were efficacious in maintaining CIDP.

Correlation of the patient's reported outcome Inflammatory-RODS with an objective metric in immune-mediated neuropathies.

BACKGROUND AND PURPOSE: There is increasing interest in using patient-reported outcome measures (PROMs) in clinical studies to capture individual changes over time. However, PROMs have also been criticized because they are entirely subjective. Our objective was to examine the relationship between a subjective PROM and an objective outcome tool in patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and gammopathy-related polyneuropathy (MGUSP). METHODS: The Inflammatory Rasch-built Overall Disability Scale (I-RODS©, a multi-item scale that examines functionality) was completed by 137 patients with newly diagnosed (or relapsing) GBS (55), CIDP (59) and MGUSP (23) who were serially examined (GBS/CIDP, T0/T1/T3/T6/T12 months; MGUSP, T0/T3/T12). Possible association between the I-RODS findings and the vigorimeter scores, an objective linear instrument to assess grip strength, was examined. RESULTS: A significant correlating trend was found between the I-RODS and grip strength scores for the overall group and in each illness, independently. CONCLUSION: The objectivity of patients' subjective report on their functional state based on a strong correlation between the I-RODS and grip strength in patients with GBS, CIDP and MGUSP has been demonstrated. These findings provide further support to use the I-RODS and grip strength in future clinical studies in these conditions.

Physician-assessed and patient-reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin.

BACKGROUND: The different perception and assessment of chemotherapy-induced peripheral neurotoxicity (CIPN) between healthcare providers and patients has not yet been fully addressed, although these two approaches might eventually lead to inconsistent, possibly conflicting interpretation, especially regarding sensory impairment. PATIENTS AND METHODS: A cohort of 281 subjects with stable CIPN was evaluated with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC v. 2.0) sensory scale, the clinical Total Neuropathy Score (TNSc©), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sumscore (mISS) and the European Organization for Research and Treatment of Cancer CIPN specific self-report questionnaire (EORTC QOL-CIPN20). RESULTS: Patients' probability estimates showed that the EORTC QLQ-CIPN20 sensory score was overall more highly related to the NCI-CTC sensory score. However, the vibration perception item of the TNSc had a higher probability to be scored 0 for EORTC QLQ-CIPN20 scores lower than 35, as vibration score 2 for EORTC QLQ-CIPN20 scores between 35 and 50 and as grade 3 or 4 for EORTC QLQ-CIPN20 scores higher than 50. The linear models showed a significant trend between each mISS item and increasing EORTC QLQ-CIPN20 sensory scores. CONCLUSION: None of the clinical items had a perfect relationship with patients' perception, and most of the discrepancies stood in the intermediate levels of CIPN severity. Our data indicate that to achieve a comprehensive knowledge of CIPN including a reliable assessment of both the severity and the quality of CIPN-related sensory impairment, clinical and PRO measures should be always combined.

The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS: After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS: Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION: Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.

Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel.

Mutations in the skeletal muscle sodium channel gene (SCN4A) have been described in paramyotonia congenita (PMC) and hyperkalaemic periodic paralysis (HPP). We have found two mutations in SCN4A which affect regions of the sodium channel not previously associated with a disease phenotype. Furthermore, affected family members display an unusual mixture of clinical features reminiscent of PMC, HPP and of a third disorder, myotonia congenita (MC). The highly variable individual expression of these symptoms, including in some cases apparent non-penetrance, implies the existence of modifying factors. Mutations in SCN4A can produce a broad range of phenotypes in muscle diseases characterized by episodic abnormalities of membrane excitability.

Open muscle biopsy in suspected myopathy: diagnostic yield and clinical utility.

BACKGROUND: The purpose of the study was to investigate the diagnostic yield and clinical utility of open muscle biopsy and to identify pre-biopsy factors that might predict useful clinical results for suspected myopathy. METHODS: Two-hundred fifty-eight muscle biopsies, performed for investigation of suspected myopathy, were evaluated. RESULTS: A specific clinical diagnosis following muscle biopsy was made in 43% of cases. As a result of the biopsy, clinical diagnosis was changed in 47% and treatment was changed in 33% of cases. Results either led to a specific clinical diagnosis or changed the diagnosis/treatment in 74% of patients. Positive family history of myopathy and findings of myopathic irritability on electromyography had a negative predictive value for diagnosis change. CONCLUSIONS: Open muscle biopsy is useful in myopathy evaluation in the modern genetic era.

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - first revision.

BACKGROUND: Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been previously published in European Journal of Neurology and Journal of the Peripheral Nervous System. OBJECTIVES: To revise these guidelines. METHODS: Disease experts, including a representative of patients, considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed in an iterative fashion. RECOMMENDATIONS: The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (i) intravenous immunoglobulin (IVIg) (Recommendation Level A) or corticosteroids (Recommendation Level C) should be considered in sensory and motor CIDP; (ii) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (iii) if IVIg and corticosteroids are ineffective, plasma exchange (PE) should be considered (Recommendation Level A); (iv) if the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (v) symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).

Clinical applications of intravenous immunoglobulins in neurology.

Intravenous immunoglobulin (IVIg) is used increasingly in the management of patients with neurological conditions. The efficacy and safety of IVIg treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) have been established clearly in randomized controlled trials and summarized in Cochrane systematic reviews. However, questions remain regarding the dose, timing and duration of IVIg treatment in both disorders. Reports about successful IVIg treatment in other neurological conditions exist, but its use remains investigational. IVIg has been shown to be efficacious as second-line therapy in patients with dermatomyositis and suggested to be of benefit in some patients with polymyositis. In patients with inclusion body myositis, IVIg was not shown to be effective. IVIg is also a treatment option in exacerbations of myasthenia gravis. Studies with IVIg in patients with Alzheimer's disease have reported increased plasma anti-Abeta antibody titres associated with decreased Abeta peptide levels in the cerebrospinal fluid following IVIg treatment. These changes at the molecular level were accompanied by improved cognitive function, and large-scale randomized trials are under way.

Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy.

To develop diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP), a retrospective series of patients' records diagnosed by sexpert consensus as CIDP or other chronic polyneuropathies were analyzed. Classification and regression tree analysis was applied to 150 patients to derive a classification rule. According to the rule, diagnosis of CIDP required that a patient have a chronic non-genetic polyneuropathy, progressive for at least eight weeks, without a serum paraprotein and either 1) recordable compound muscle action potentials in > or =75% of motor nerves and either abnormal distal latency in >50% of nerves or abnormal motor conduction velocity in >50% of nerves or abnormal F wave latency in >50% of nerves; or 2) symmetrical onset of motor symptoms, symmetrical weakness of four limbs, and proximal weakness in > or =1 limb. When validated in 117 patients, the rule had 83% sensitivity (95% confidence interval 69%-93%) and 97% specificity (95% confidence interval 89%-99%) and performed better than published criteria.

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy.

Several diagnostic criteria for multifocal motor neuropathy have been proposed in recent years and a beneficial effect of intravenous immunoglobulin (IVIg) and various other immunomodulatory drugs has been suggested in several trials and uncontrolled studies. The objectives were to prepare consensus guidelines on the definition, investigation and treatment of multifocal motor neuropathy. Disease experts and a patient representative considered references retrieved from MEDLINE and the Cochrane Library in July 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed good practice points to define clinical and electrophysiological diagnostic criteria for multifocal motor neuropathy and investigations to be considered. The principal recommendations and good practice points were: (i) IVIg (2 g/kg given over 2-5 days) should be considered as the first line treatment (level A recommendation) when disability is sufficiently severe to warrant treatment. (ii) Corticosteroids are not recommended (good practice point). (iii) If initial treatment with IVIg is effective, repeated IVIg treatment should be considered (level C recommendation). The frequency of IVIg maintenance therapy should be guided by the individual response (good practice point). Typical treatment regimens are 1 g/kg every 2-4 weeks or 2 g/kg every 4-8 weeks (good practice point). (iv) If IVIg is not or not sufficiently effective then immunosuppressive treatment may be considered. Cyclophosphamide, ciclosporin, azathioprine, interferon beta1a, or rituximab are possible agents (good practice point). (v) Toxicity makes cyclophosphamide a less desirable option (good practice point).

Tramadol for neuropathic pain.

BACKGROUND: Peripheral neuropathic pains often include symptoms such as burning or shooting sensations, abnormal sensitivity to normally painless stimuli, or an increased sensitivity to normally painful stimuli. Neuropathic pain is a common symptom in many diseases of the peripheral nervous system. OBJECTIVES: We aimed to review systematically the evidence from randomised controlled trials for the efficacy of tramadol in treating neuropathic pain. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (June 2005), MEDLINE (January 1966 to June 2005), EMBASE (January 1980 to June 2005), and LILACS (January 1982 to June 2005) for randomised and quasi-randomised controlled trials. We also searched bibliographies of published trials. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials comparing tramadol with placebo, other pain relieving treatment, or no treatment in people of both sexes and all ages with neuropathic pain of all degrees of severity. DATA COLLECTION AND ANALYSIS: Two authors extracted data and scored trial quality. We calculated relative risks and numbers needed to treat for effectiveness and adverse effects. MAIN RESULTS: We identified six eligible trials, four comparing tramadol with placebo, one comparing tramadol with clomipramine, and one comparing tramadol with morphine. All four trials comparing tramadol with placebo showed a significant reduction in neuropathic pain with tramadol. Three of the trials which compared tramadol to placebo (total 269 participants) were combined in a meta-analysis. The number needed to treat with tramadol compared to placebo to reach at least 50% pain relief was 3.8 (95% confidence interval 2.8 to 6.3). There were insufficient data to draw conclusions about the effectiveness of tramadol compared to either clomipramine or morphine.Only one trial considered subcategories of neuropathic pain. It found a significant therapeutic effect of tramadol on paraesthesiae, allodynia, and touch evoked pain. Numbers needed to harm were calculated for side effects resulting in withdrawal from the placebo controlled trials. Three trials provided these data, and the combined number needed to harm was 8.3 (95% confidence interval 5.6 to 17). AUTHORS' CONCLUSIONS: Tramadol is an effective treatment for neuropathic pain.

Phase I and pharmacologic study of paclitaxel and cisplatin with granulocyte colony-stimulating factor: neuromuscular toxicity is dose-limiting.

PURPOSE: To determine the maximum-tolerated doses (MTD), the principal toxicities, and the pharmacologic behavior of high doses of Taxol (paclitaxel; Bristol-Myers Squibb, New York, NY) combined with cisplatin and granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS: Untreated and minimally pretreated solid-tumor patients received 24-hour infusions of Taxol on day 1 followed by cisplatin on day 2 and G-CSF, 5 micrograms/kg/d subcutaneously (SC), beginning on day 3. Treatment was repeated every 3 weeks. Starting doses of Taxol and cisplatin were 135 and 75 mg/m2, respectively. RESULTS: The development of a severe peripheral neuropathy and/or severe myalgias precluded the chronic administration of Taxol and cisplatin with G-CSF at doses greater than 250 mg/m2 and 75 mg/m2, respectively. At this dose, the mean Taxol steady-state plasma concentration (Css) exceeds concentrations capable of inducing pertinent antimicrotubule effects in vitro. The severity of the neuropathy was related to the cumulative dose of Taxol, the magnitude of the dose administered during each treatment, and the presence of a pre-existing medical disorder associated with peripheral neuropathy. A proximal myopathy of modest severity also was documented. Although severe neutropenia occurred frequently, especially at the MTD, it was rarely associated with fever (8% of courses), and absolute neutrophil counts (ANCs) less than 500/microL never persisted for more than 5 days. Responses were noted in non-small-cell lung cancer (NSCLC) and head and neck, breast, and esophageal cancers. CONCLUSION: Taxol and cisplatin doses of 250 mg/m2 and 75 mg/m2, respectively, can be administered repetitively with G-CSF to untreated and minimally pretreated patients. However, these doses are not recommended for patients with pre-existing neuropathies until additional experience in high-risk patients is obtained. Although this Taxol dose is nearly 85% higher than the dose that can be combined with cisplatin in the absence of G-CSF, this high-dose regimen should not be used outside the investigational setting until a dose-response relationship has been demonstrated for Taxol in randomized clinical trials.

Peripheral neuropathy in diabetic monkeys.

Peripheral neuropathy is a significant complication of human diabetes and a source of morbidity. Appropriate experimental models may aid in understanding its pathogenesis and in developing therapeutic strategies. We sought to determine whether spontaneously diabetic obese adult monkeys developed peripheral neuropathy and whether it occurred early or late in relation to the onset of hyperglycemia. We studied nerve conduction in both motor (peroneal, median, and ulnar) and sensory (median and ulnar) nerves in 13 adult male rhesus monkeys, 4 overtly diabetic and 9 nondiabetic (mean age 21 +/- 2 and 16 +/- 2 yr, respectively, NS; mean fasting plasma glucose 14.5 +/- 3.4 and 4.4 +/- 0.6 mM, P = .001). The diabetic animals had significantly reduced motor conduction velocities and prolonged F-wave latencies. Motor-evoked amplitudes did not differ. In the diabetic monkeys, nerve conduction times were increased in motor fibers, which could be identified as early as 2 yr after the onset of hyperglycemia. These abnormalities are similar to those seen in humans and suggest further study of these animals as a primate model of human diabetic neuropathy.

Neurotoxicity of Taxol.

Neurotoxicity, manifested primarily by a motor and sensory polyneuropathy, is the principal nonhematological side effect of Taxol. Available evidence suggests that Taxol produces a toxic effect involving either axons or ganglion cell bodies, or both, rather than a myelinopathy. As with other toxic polyneuropathies, patients with preexisting peripheral neuropathies, such as those caused by diabetes mellitus or ethanol, appear to be particularly predisposed to developing neurological toxicity. The incidence and severity of the neuropathic manifestations also appear to be related to the Taxol dose level, the cumulative dose of Taxol, and possibly to the use of Taxol in combination with cisplatin. Rarely, manifestations of autonomic and central nervous system dysfunction occur. Taxol also induces myalgias in the peri-treatment period, especially when used in high doses, and a myopathy has been noted in patients treated with high doses of Taxol administered alone and in combination with cisplatin. Although dose-response relationships for Taxol have not been clearly established, these neuromuscular effects are likely to become a significant clinical problem if higher doses of Taxol are used with hematopoietic colony-stimulating factors. The neuromuscular effects of Taxol, including symptoms, physical and electrophysiological manifestations, and predisposing factors, as well as agents that may be used for neuroprotection, are discussed in this report.

Epidermal nerve fiber density: normative reference range and diagnostic efficiency.

BACKGROUND: The sensitivity of neuron-specific antibodies permit the identification of the small unmyelinated nerve fibers within the skin. OBJECTIVES: To develop a reference range of epidermal nerve fiber density in humans, and to evaluate their diagnostic efficiency for sensory neuropathies. METHODS: Ninety-eight normal controls (age range, 13-82 years) were examined with both directed neurologic examinations and quantitative sensory testing. The diagnostic utility was examined in 20 patients with sensory neuropathies. Each subject had 2 punch biopsies performed at each site in the thigh and distal part of the leg (total of 392 biopsies). After formalin fixation, 50-microm-thick free-floating sections were stained with a polyclonal antibody to neuron-specific ubiquitin hydrolase, anti-protein gene product 9.5. We enumerated intraepidermal nerve fibers per millimeter to derive a "linear density." The linear density technique was validated against a stereological technique that used the fractionator to measure the total length of intraepidermal nerve fibers per 3-mm punch. RESULTS: The biopsy technique was well tolerated, with no notable complications. The linear density quantitation was rapid and had high intraobserver and interobserver reliability. We determined that the density of intraepidermal fibers in normal controls was 21.1+/-10.4 per millimeter (mean +/- SD) in the thigh (fifth percentile, 5.2 per millimeter), and was 13.8+/-6.7 per millimeter at the distal part of the leg (fifth percentile, 3.8 per millimeter). Significantly higher intraepidermal fiber densities were seen in the youngest group (P = .004), and we observed no significant effect of race, sex, height, or weight. The density at the thigh was significantly correlated with that at the distal part of the leg (P = .01) and was consistently higher by about 60%, a reflection of the normal proximal-distal gradient. The results obtained with stereology and the linear density correlated significantly (P=.001), providing internal validation for the technique. Epidermal nerve fiber density was significantly reduced (P = .001) in patients with sensory neuropathies. With a cutoff derived from the fifth percentile of the normative range for the distal part of the leg, the technique had a positive predictive value of 75%, a negative predictive value of 90%, and a diagnostic efficiency of 88%. CONCLUSIONS: We have established a reference range for intraepidermal nerve fiber density in normal humans by means of a simple quantitation method based on enumeration of individual intraepidermal nerve fibers on vertical sections of punch skin biopsy specimens stained with the sensitive panaxonal marker anti-protein gene product 9.5. The utility of the density measurement was confirmed for sensory neuropathy with a diagnostic efficiency of 88%. Skin biopsies may be useful to assess the spatial distribution of involvement in peripheral nerve disease and the response to neurotrophic and other restorative therapies.

Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex.

The most common type of peripheral neuropathy associated with human immunodeficiency virus (HIV) infection, predominantly sensory neuropathy, affects 10-30% of patients with acquired immunodeficiency syndrome (AIDS). From 40 individuals with peripheral neuropathy and HIV infection, we have identified 26 patients with this syndrome. All had constitutional symptoms when neuropathic symptoms developed; 20 had AIDS and six had AIDS-related complex. The most common complaint was pain on the soles. Paresthesias were frequent and usually involved the entire foot. Signs of peripheral neuropathy were present in all; the most frequent finding was absent or reduced ankle reflexes. Electrophysiologic studies revealed abnormal sensory and motor conduction, studies suggesting a dying-back axonopathy. Over time, the neuropathy progressed in all except one patient with ARC, who had spontaneous subjective improvement. Tricyclic antidepressants provided partial symptomatic relief. In three patients, the neuropathy did not change during azidothymidine treatment. Predominantly sensory neuropathy in HIV infection appears to be a distal axonal degeneration primarily involving sensory neurons. The mechanism is unknown, but the neuropathy is associated with the late manifestations of HIV infection.

Neopterin and interferon-gamma in serum and cerebrospinal fluid of patients with HIV-associated neurologic disease.

We measured the levels of interferon-gamma (IFN-gamma) and neopterin in the serum and cerebrospinal fluid of 121 human immunodeficiency virus-seropositive (HIV+) and 62-seronegative (HIV-) individuals evaluated for neurologic disease. CSF levels of IFN-gamma and serum and CSF levels of neopterin were higher in HIV+ than in HIV- individuals. Patients with HIV- related meningitis and with opportunistic CNS infections had higher serum neopterin levels than HIV+ asymptomatic individuals. CSF levels of IFN-gamma were slightly higher in CSF of HIV+ individuals in all groups (0.31 +/- 0.03 U/ml) than in HIV- individuals (0.12 +/- 0.03). CSF levels of neopterin were similar in HIV+ asymptomatic individuals (6.9 +/- 0.7 nmol/l) and HIV- individuals (5.9 +/- 1.1), but were elevated in those HIV-infected individuals with neurologic disease, particularly patients with HIV-associated meningitis (72.1 +/- 13.3 nmol/l), opportunistic CNS infections (36 +/- 9.1), and inflammatory demyelinating polyneuropathies (32.4 +/- 17.2). Levels of neopterin correlated positively with levels of soluble interleukin 2 receptor and soluble CD8, 2 additional indicators of immune activation. In the absence of neurologic disease, levels of IFN-gamma and neopterin in both serum and CSF were stable for up to 4 years after seroconversion. These data suggest that increased CSF neopterin is associated with HIV-associated neurologic disease.

Chronic demyelinating polyneuropathy in systemic lupus erythematosus.

Mononeuritis multiplex and acute demyelinating polyneuropathy (Guillain-Barré syndrome) are well known in systemic lupus erythematosus (SLE). Chronic acquired demyelinating polyneuropathy has been reported rarely in SLE. Two young women had monophasic progressive weakness, areflexia, elevated CSF protein, and slow nerve conduction velocities as the first manifestation of SLE. Sural nerve biopsy in one patient revealed mild loss of myelinated fibers and an increased number of thinly myelinated fibers. Steroid therapy led to improvement in both patients. These patients demonstrate that chronic demyelinating polyneuropathy can be an unusual presentation of SLE, even preceding characteristic systemic disease by months.

Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases.

The authors report the use mycophenolate mofetil (MM) in the treatment of neuromuscular diseases. Thirty-eight patients (32 with MG, three with inflammatory myopathy, and three with chronic acquired demyelinating neuropathy) were treated with MM for an average duration of 12 months. All patients tolerated MM without major side effects. Twenty-four patients improved either in their functional status or in their ability to reduce corticosteroid dose. Mean time to improvement was 5 months.

Conjugal amyotrophic lateral sclerosis: report of a young married couple.

We report a 38-year-old nurse who developed amyotrophic lateral sclerosis (ALS) beginning in September 1990. In May 1991, her 38-year-old husband developed dysarthria, which progressed to typical ALS. This is the fourth report in the literature of conjugal ALS occurring outside of Guam. Although this event is most likely due to coincidence, exogenous agents should be considered in the etiology of ALS.