John W. Engstrom

Prevalence and clinical features of HTLV neurologic disease in the HTLV Outcomes Study

Background: Almost 20 years after its discovery, the prevalence and clinical course of human T-lymphotropic virus type I (HTLV-I)–associated myelopathy (HAM, also known as tropical spastic paraparesis [TSP]) remain poorly defined. Whereas the causative association of HTLV-I and HAM/TSP is generally recognized, controversy still surrounds the relationship between HTLV-II and HAM/TSP. Methods: The HTLV Outcomes Study (HOST—formerly Retrovirus Epidemiology Donor Study [REDS]) is a prospective cohort study including 160 patients with HTLV-I, 405 patients with HTLV-II, and 799 uninfected controls who have been followed every 2 years since 1990–1992. Clinical outcomes are measured by health interviews and examinations, and blood samples are obtained. Results: Six cases of HTLV-I–associated myelopathy (3.7%, 95% CI 1.4 to 8.0) and four cases of HTLV-II myelopathy (1.0%, 95% CI 0.3 to 2.5) have been diagnosed since the formation of the cohort. There have been no cases of HAM/TSP diagnosed among HTLV-negative subjects (0.0%, 95% CI 0.0 to 0.5). Clinical features of the cases include lower extremity hyperreflexia, variably associated with weakness, spasticity, and bladder dysfunction. Conclusions: Systematic screening of HTLV-infected blood donors reveals a high prevalence of HAM/TSP. The clinical course of HAM/TSP appears highly variable. HTLV-II–associated myelopathy generally presents with milder and more slowly progressive signs and symptoms.

HTLV-associated myelopathy in a cohort of HTLV-I and HTLV-II-infected blood donors

Article abstract-Objective: HTLV-I-associated myelopathy (HAM) is a slowly progressive spastic paraparesis caused by infection with human T-lymphotropic virus type I (HTLV-I). The prevalence of HAM among those infected with HTLV-I is poorly defined, and the association of a similar myelopathy with HTLV-II infection has not been confirmed. Design: Cross-sectional examination of HTLV-I, HTLV-II, and control subjects from the baseline visit of a cohort study. Setting/subjects: Persons testing HTLV seropositive at the time of blood donation at five U.S. blood centers, their seropositive sex partners, and a matched control group of HTLV seronegative blood donors. Measurements: HTLV-I and HTLV-II were differentiated by serology and/or polymerase chain reaction. All subjects received systematic neurologic screening examinations. Results: A diagnosis of myelopathy was confirmed in four of 166 HTLV-I subjects (2.4%, 95% confidence interval 0.7%, 6.1%) and in one of 404 HTLV-II subjects (0.25%, 95% confidence interval 0.0%, 0.6%). None of the 798 controls had a similar myelopathy, although one had longstanding typical multiple sclerosis. Conclusions: Our data also suggest that HAM occurs more frequently among HTLV-I-infected subjects than reported by previous studies. The HTLV-II infected myelopathy patient identified in this cohort, together with three other case reports in the literature, implies a pathogenic role for this human retrovirus. The diagnosis of HTLV-associated myelopathy should be considered in cases of spastic paraparesis or neurogenic bladder when risk factors for HTLV-I or HTLV-II infection are present. NEUROLOGY 1997;48: 315-320

Cerebral infarctions and transiet neurologic deficits associated with acquired immunodeficiency syndrome

PURPOSE Little information is available concerning the clinical importance of cerebral infarction in patients with acquired immunodeficiency syndrome (AIDS). The purpose of this retrospective study was two-fold: (1) to determine the frequency and clinical characteristics of cerebral infarction and transient neurologic deficits (TNDs) among patients with AIDS; and (2) to identify specific patient subgroups at risk for such complications and whether there were underlying associated diseases requiring specific therapy. PATIENTS AND METHODS Neurology inpatient and consult service records, neuropathology reports, and the University of California, San Francisco, AIDS computerized registry were used in identifying study cases. Information on demographic background, associated clinical diagnoses, presenting neurologic symptoms and signs, laboratory results, pathologic findings, and clinical follow-up was obtained from each patients medical record. RESULTS Twenty-five patients with AIDS (mean age, 38) having clinical or pathologic findings suggestive of focal cerebral ischemia or infarction were identified. Ten patients had non-hemorrhagic cerebral infarctions, 13 had acute TNDs, and two had both. Cerebral infarction was associated with central nervous system (CNS) infections (cryptococcus, four; tuberculosis, one; zoster vasculitis, one) and cardiogenic embolism (one). TNDs were associated with toxoplasmosis (four), cerebral infarction (two), cryptococcal meningitis (one), vasculitis (one), and CNS Kaposis sarcoma (one). A presumptive cause was absent in five cases of cerebral infarction and eight of TND. All five patients with pathologically proven macroscopic cerebral infarcts were diagnosed clinically before death. CONCLUSIONS We conclude the following: (1) AIDS patients, especially given their young age, appear to be increased risk for cerebral infarction and TND. (2) Cerebral infarction and TND may be the initial presentation of AIDS. (3) TND and cerebral infarction often signify treatable CNS infection among AIDS patients. (4) The causes of AIDS-related cerebral infarction and TND are unknown in many cases.

Statistical motor unit number estimation : Reproducibility and sources of error in patients with amyotrophic lateral sclerosis

The reliability of motor unit number estimation (MUNE) for assessment of the long‐term course of ALS is dependent on the reproducibility of the technique. We report our results with the statistical method of MUNE on the ulnar nerve/hypothenar muscle in 16 ALS patients who were studied on 52 occasions. On each occasion, MUNE was performed twice with one electrode placement and once with a different placement. For each MUNE, mean surface motor unit potential amplitude was determined within three different recording ranges or windows at different stimulus intensities. The MUNE results had excellent reproducibility with coefficients of variation of 19% and test–retest correlation coefficients from 0.75 to 0.86. With examination of sources for variability, the reproducibility of statistical MUNE is not affected by minor variation in stimulation and recording electrode placement but may be improved by modifying methods for recording window selection. The high reproducibility of statistical MUNE supports its reliability for estimating the rate of motor unit loss in ALS.

Magnetic resonance neurography for the evaluation of peripheral nerve, brachial plexus, and nerve root disorders.

OBJECT Treatment of spinal and peripheral nerve lesions relies on localization of the pathology by the use of neurological examination, spinal MR imaging and electromyography (EMG)/nerve conduction studies (NCSs). Magnetic resonance neurography (MRN) is a novel imaging technique recently developed for direct imaging of spinal and peripheral nerves. In this study, the authors analyzed the role of MRN in the evaluation of spinal and peripheral nerve lesions. METHODS Imaging studies, medical records, and EMG/NCS results were analyzed retrospectively in a consecutive series of 191 patients who underwent MRN for spinal and peripheral nerve disorders at the University of California, San Francisco between March 1999 and February 2005. Ninety-one (47.6%) of these patients also underwent EMG/NCS studies. RESULTS In those who underwent both MRN and EMG/NCS, MRN provided the same or additional diagnostic information 32 and 45% of patients, respectively. Magnetic resonance neurograms were obtained at a median of 12 months after the onset of symptoms. The utility of MRN correlated with the interval between the onset of symptoms to MRN. Twelve patients underwent repeated MRN for serial evaluation. The decrease in abnormal signal detected on subsequent MRN correlated with time from onset of symptoms and the time interval between MRN, but not with resolution of symptoms. Twenty-one patients underwent MRN postoperatively to assess persistent, recurrent, or new symptoms; of these 3 (14.3%) required a subsequent surgery. CONCLUSIONS Magnetic resonance neurography is a valuable adjunct to conventional MR imaging and EMG/NCS in the evaluation and localization of nerve root, brachial plexus, and peripheral nerve lesions. The authors found that MRN is indicated in patients: 1) in whom EMG and traditional MR imaging are inconclusive; 2) who present with brachial plexopathy who have previously received radiation therapy to the brachial plexus region; 3) who present with brachial plexopathy and have systemic tumors; and 4) in patients under consideration for surgery for peripheral nerve lesions or after trauma. Magnetic resonance neurography is limited by the size of the nerve trunk imaged and the timing of the study.

Neurologic abnormalities in HTLV-I– and HTLV-II–infected individuals without overt myelopathy

Background: Human T-lymphotropic virus (HTLV) type I is the causative agent of HTLV-associated myelopathy (HAM)/tropical spastic paraparesis, and a number of HAM cases with HTLV-II infection have also been reported. However, despite some reports, it is unclear whether HTLV-I or -II infection is associated with other neurologic manifestations. Methods: An analysis of medical histories and screening neurologic examinations from a prospective cohort of 153 HTLV-I, 388 HTLV-II, and 810 HTLV-seronegative individuals followed up for means of 11.5, 12.0, and 12.2 years was performed. Participants diagnosed with HAM were excluded. We calculated odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, sex, race or ethnicity, income, educational attainment, body mass index, alcohol and cigarette consumption, injection drug use, diabetes, and hepatitis C virus status, using generalized estimating equations for repeated measures. Results: HTLV-I and -II participants were more likely than seronegative participants to have leg weakness (ORs 1.67 [95% CI 1.28–2.18] and 1.44 [1.16–1.78]), impaired tandem gait (ORs 1.25 [95% CI 1.07–1.47] and 1.45 [1.27–1.64]), Babinski sign (ORs 1.54 [95% CI 1.13–2.08] and 1.51 [1.18–1.93]), impaired vibration sense (ORs 1.16 [95% CI 1.01–1.33] and 1.27 [1.14–1.42]), and urinary incontinence (ORs 1.45 [95% CI 1.23–1.72] and 1.70 [1.50–1.93]). For both HTLV-I and -II participants, higher odds of sensory neuropathy by monofilament examination were no longer significant after adjustment for confounding. Conclusions: These results provide strong evidence that human T-lymphotropic virus (HTLV)-I and -II are associated with a spectrum of predominantly motor abnormalities in patients without overt HTLV-associated myelopathy. Further investigation of the clinical course and etiology of these abnormalities is warranted.

Neurohospitalists: An emerging model for inpatient neurological care

Over the past decade, the hospitalist model has become a dominant system for the delivery of general adult and pediatric inpatient care. Similar forces, including national mandates to improve safety and quality and intense pressure to safely reduce length of hospital stays, that led to the remarkable growth of hospitalist medicine are now exerting pressure on neurologists. A neurohospitalist model, in which inpatient neurology specialists deliver high‐quality and efficient care to neurology patients, is emerging to meet these challenges. Benefits of this system may include more frequent, timely neurology consultations in the hospital and emergency department, as well as improved quality of inpatient neurological education for residents and medical students. Challenges will involve defining the relationship of neurohospitalists with primary stroke centers, the economic feasibility of such neurohospitalist systems, and how to train members of this new field. A neurohospitalist model of care is an emerging idea in neurology that would overcome many regulatory, educational, and economic challenges facing neurologists; further research is needed to gauge the effects of this innovative approach. Ann Neurol 2008;63:135–140

Comparison of transthecal and subcutaneous single-injection digital block techniques

A randomized double-blinded study was performed on 20 normal volunteers to evaluate 2 different techniques of single-injection digital anesthesia. Single-injection transthecal digital block technique was used to anesthetize 1 index finger and single-injection subcutaneous technique to block the other index finger. Pain and light touch were evaluated and sensory nerve-conduction studies were performed on both index fingers. These data were obtained prior to the nerve blocks and then at 10-minute intervals until recovery from the anesthesia. The method of anesthesia was found to have no effect on the distribution, onset, and duration of anesthesia. Median and radial nerve sensory nerve action potential amplitude reductions following digital anesthesia were also not influenced by the technique of anesthesia. Single-injection subcutaneous block was found to be easier to administer and to produce less pain during and 24 hours after injection than did the single-injection transthecal technique.

Pleasurable emotional response to music: A case of neurodegenerative generalized auditory agnosia

Recent functional neuroimaging studies implicate the network of mesolimbic structures known to be active in reward processing as the neural substrate of pleasure associated with listening to music. Psychoacoustic and lesion studies suggest that there is a widely distributed cortical network involved in processing discreet musical variables. Here we present the case of a young man with auditory agnosia as the consequence of cortical neurodegeneration who continues to experience pleasure when exposed to music. In a series of musical tasks, the subject was unable to accurately identify any of the perceptual components of music beyond simple pitch discrimination, including musical variables known to impact the perception of affect. The subject subsequently misidentified the musical character of personally familiar tunes presented experimentally, but continued to report that the activity of ‘listening’ to specific musical genres was an emotionally rewarding experience. The implications of this case for the evolving understanding of music perception, music misperception, music memory, and music-associated emotion are discussed.

Education Research: Neurology training reassessed The 2011 American Academy of Neurology Resident Survey results

Objective: To assess the strengths and weaknesses of neurology resident education using survey methodology. Methods: A 27-question survey was sent to all neurology residents completing residency training in the United States in 2011. Results: Of eligible respondents, 49.8% of residents returned the survey. Most residents believed previously instituted duty hour restrictions had a positive impact on resident quality of life without impacting patient care. Most residents rated their faculty and clinical didactics favorably. However, many residents reported suboptimal preparation in basic neuroscience and practice management issues. Most residents (71%) noted that the Residency In-service Training Examination (RITE) assisted in self-study. A minority of residents (14%) reported that the RITE scores were used for reasons other than self-study. The vast majority (86%) of residents will enter fellowship training following residency and were satisfied with the fellowship offers they received. Conclusions: Graduating residents had largely favorable neurology training experiences. Several common deficiencies include education in basic neuroscience and clinical practice management. Importantly, prior changes to duty hours did not negatively affect the resident perception of neurology residency training.