Mitchell T. Wallin

Neurocysticercosis in the United States: Review of an important emerging infection

Objective: To review published clinical studies on neurocysticercosis (NCC) in the United States over the past two decades and comment on epidemiologic trends and treatment. Methods: This review is based on a search of the literature citing NCC cases diagnosed in the United States utilizing PUBMED for the years 1980 through early 2004. Case series, case reports, epidemiologic studies, and treatment of NCC were evaluated. Results: A total of 1,494 patients with NCC were reported in the United States among large case series (n > 20) between 1980 and early 2004. Common onset symptoms for these patients included seizures (66%), hydrocephalus (16%), and headaches (15%). The majority presented with parenchymal NCC (91%), with the remainder having ventricular cysts (6%), subarachnoid cysts (2%), and spinal cysts (0.2%). A total of 76 cases of NCC were likely acquired within the United States during the period of this review. A higher risk for acquiring NCC has been documented in patients who have traveled to endemic regions, are of Hispanic ethnicity, and have contact with Taenia solium tapeworm carriers. Conclusions: An increasing number of NCC cases have been reported in the US literature over the past 50 years, suggesting that the prevalence of this disease may be on the rise. Because neurologists are often involved with the diagnosis and management of NCC in the United States, it is important that they become familiar with this disorder, as they will play an important role in efforts to control the disease.

The Gulf War era multiple sclerosis cohort: age and incidence rates by race, sex and service

We characterize here a new nationwide incident cohort of multiple sclerosis from the US military-veteran population. This cohort provides an update to the only other US nationwide incidence study of multiple sclerosis performed during the 1970s. Medical records and data from the Department of Defense and Department of Veterans Affairs for cases of multiple sclerosis who served in the military between 1990, the start of the Gulf War era, and 2007 and who were service-connected for this disorder by the Department of Veterans Affairs from 1990 on, were reviewed. A total of 2691 patients were confirmed as having multiple sclerosis: 2288 definite, 190 possible, 207 clinically isolated syndrome and six neuromyelitis optica. Overall racial categories were White, Black and other, which included all Hispanics. There were 1278 White males and 556 females; 360 Black males and 296 females; and 200 others, 153 (77%) of whom were Hispanic. Mean age at onset of 30.7 years did not differ significantly by race or sex. Age at onset was 17-50 years in 99%, the same age range as 99% of the military. Average annual age specific (age 17-50 years) incidence rates per 100 000 for the entire series were 9.6 with 95% confidence interval of 9.3-10.0. Rates for Blacks were highest at 12.1 with confidence interval 11.2-13.1, Whites were 9.3 (interval 8.9-9.8) and others 6.9 (interval 6.0-7.9). For 83 Hispanics defined for 2000-07, the rate was 8.2 (interval 6.5-10.1). Much smaller numbers gave rates of 3.3 for Asian/Pacific Islanders and 3.1 for native Americans. Rates by sex for Whites were 7.3 and 25.8 male and female, respectively, for Blacks 8.4 and 26.3, and for Hispanics 6.6 and 17.0. Rates by service were high for Air Force (10.9) and Army (10.6), medium for Navy (9.1) and Coast Guard (7.9), and low for Marines (5.3). Relative risk of multiple sclerosis was 3.39 female:male and 1.27 Black:White. These new findings indicate that females of all races now have incidence rates for multiple sclerosis some three times those of their male counterparts and that among these groups, Blacks have the highest and others (probably including Hispanics) the lowest incidence rates regardless of sex or service. The low rate for Marines is unexplained. This Gulf War era multiple sclerosis cohort provides a unique resource for further study.

Depression and multiple sclerosis: Review of a lethal combination

Depression is the most frequent psychiatric disorder in multiple sclerosis (MS) patients. The etiology of depression is multifactorial and likely associated with psychosocial stress, focal demyelinating lesions, and immune dysfunction. Proper diagnosis and severity assessment are critical prior to initiation of therapy. Patients with suicidal ideation should be referred for immediate psychiatric consultation and be closely monitored. While more therapeutic trials for depression in MS are needed, MS patients have been shown to respond to current antidepressant medications and psychotherapy. Unfortunately, patients with MS and major depression or suicidal thoughts are often underassessed and therefore not diagnosed. Unlike other aspects of MS, depression is treatable. Early intervention in depression can prevent declines in quality of life and even death from suicide. This article reviews the unique features, assessment, and treatment of depression in MS. MS care providers should vigilantly assess depression and suicide risk in their patients.

Multiple sclerosis in the Faroe Islands

Detailed questionnaires were completed in 1978–79 by 23 of the 28 then known resident Faroese multiple sclerosis (MS) patients and 127 controls. These controls were divided into 69 Group A (patient sibs and other relatives), 37 Group B (matched neighbor controls, their spouses and sibs, plus patients spouse), and 21 Group C (distant matched controls, spouses, relatives living where MS patients never resided and British troops were not encamped during the war). No differences between cases and controls were found for education, occupation, types of residence, bathing, sanitary or drinking facilities, and nature of house construction or heating. Detailed dietary histories, available for half the subjects, revealed no difference, cases versus controls, for four age periods between age 0 and 30 years, and for 16 specified foodstuffs. Animal exposures showed overall no consistent differences by location or type of animal. There was a tendency to greater exposure to British troops during the war for cases versus Groups A and B, but this did not attain statistical significance. Vaccinations for smallpox, tetanus and diphtheria were less common in the MS; no difference was found for other vaccinations. Except for a relative deficit in the cases for rubella and (insignificantly) for measles, mumps and chicken pox, reported illnesses were equally common among all groups. Operations, hospitalizations and injuries did not differentiate the groups, nor did age at menarche for women. Neurologic symptoms were significantly more common in the cases than in the controls.

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants

BACKGROUND The classic Creutzfeldt-Jakob disease (CJD), Heidenhain, and Oppenheimer-Brownell variants are sporadic CJD (sCJD) phenotypes frequently described in the literature, but many cases present with neuropsychiatric symptoms, suggesting that there may be additional sCJD phenotypes. OBJECTIVE To characterize clinical, diagnostic, and molecular features of 5 sCJD variants. DESIGN Retrospective analysis. SETTING The Johns Hopkins and Veterans Administration health care systems. PARTICIPANTS Eighty-eight patients with definite or probable sCJD. MAIN OUTCOME MEASURES Differences in age at onset, illness progression, diagnostic test results, and molecular subtype. RESULTS The age at onset differed among sCJD variants (P = .03); the affective variant had the youngest mean age at onset (59.7 years). Survival time (P < .001) and the time to clinical presentation (P = .003) differed among groups. Patients with the classic CJD phenotype had the shortest median survival time from symptom onset (66 days) and those who met criteria for the affective sCJD variant had the longest (421 days) and presented to clinicians significantly later (median time from onset to presentation, 92 days; P = .004). Cerebrospinal fluid analyses were positive for 14-3-3 protein in all of the affective variants, regardless of illness duration. Periodic sharp-wave complexes were not detected on any of the electroencephalography tracings in the Oppenheimer-Brownell group; basal ganglia hyperintensity was not detected on brain magnetic resonance imaging in this group either. All of the Heidenhain variants were of the methionine/methionine type 1 molecular subtype. CONCLUSIONS The classic CJD phenotype and the Heidenhain, Oppenheimer-Brownell, cognitive, and affective sCJD variants differ by age at disease onset, survival time, and diagnostic test results. Characteristics of these 5 phenotypes are provided to facilitate further clinicopathologic investigation that may lead to more reliable and timely diagnoses of sCJD.

Cognitive dysfunction in multiple sclerosis: Assessment, imaging, and risk factors.

Up to 70% of multiple sclerosis (MS) patients experience cognitive dysfunction during the course of their disease. The most often affected domains are attention, memory, and information processing speed. Sequelae of cognitive dysfunction include negative effects on activities of daily living, employment, and relationships. This article reviews cognitive dysfunction in MS and focuses specifically on assessment, imaging, and risk factors. A number of neuropsychological batteries have been developed specifically for assessing cognitive dysfunction in MS patients. Trade-offs in length, administrative support, and efficiency exist between the various batteries. Modern imaging techniques provide a clearer picture of MS-related damage to the central nervous system, which is the major cause of cognitive dysfunction. Additionally, candidate risk factors have been identified that may help predict which patients will develop cognitive dysfunction.

Cognitive Changes and Quality of Life in Neurocysticercosis: A Longitudinal Study

Background Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. Methodology/Principal Findings The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC. Conclusions/Significance Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment.

BLOOD PRESSURE EFFECTS OF LONG-TERM STIMULANT USE IN DISORDERS OF HYPERSOMNOLENCE

Untoward cardiovascular effects have been implicated as a deterrent to long‐term central nervous system (CNS) stimulant use in disorders of hypersomnolence. In this study, we reviewed the relationship between blood pressure and long‐term stimulant use. Medical records of 54 patients with narcolepsy and idiopathic CNS hyper‐ somnolence (ICH) were reviewed. The overall mean number of months of follow‐up for the entire group was 45.6 (95% CI: 42–49). Both simple linear regression and multiple regression utilizing generalized estimating equations were used to show relationships between blood pressure (BP), time and other covariates. In the simple linear regression model, the average slope of the line of systolic BP (SBP) on time for the entire group was 0.06 (95% CI: ‐0.09, 0.13) and the line of diastolic BP (DBP) on time was 0.01 (95% CI: ‐0.05, 0.07). Two multiple regression equations were fitted for the continuous response variables SBP and DBP. Covariates in the model included: time, hypertension, weight at baseline, weight, SBP baseline (SBPBL), DBP baseline (DBPBL), high vs. low dose stimulant therapy and age at starting treatment. For SBP, the covariates weight at baseline, weight and SBPBL were significant (P< 0.05) predictors. For DBP, covariates reaching statistical significance (P< 0.05) included weight and DBPBL. There was no significant change in SBP or DBP over time in either model. Two different statistical models support the conclusion that there was no significant change in SBP or DBP over time in this population.

Multiple sclerosis in the Faroe Islands. 8. Notifiable diseases.

Wallin MT, Heltberg A, Kurtzke JF. Multiple sclerosis in the Faroe Islands. 8. Notifiable diseases.
Acta Neurol Scand: 2010: 122: 102–109.
© 2009 The Authors Journal compilation

Treatment of Multiple Sclerosis–Related Cognitive Problems With Adjunctive Modafinil: Rationale and Preliminary Supportive Data

In patients with multiple sclerosis (MS), attention and information-processing-speed impairment contribute to dysfunction in other cognitive domains (learning, memory). Treatment for MS-related attention and processing-speed deficits may have dual benefits: improvement of function in these domains and in overall cognitive efficiency. The objective of this study was to determine whether adjunctive treatment of fatigue with modafinil ameliorates deficits in attention and cognitive domains reliant on attention. Relapsing-remitting MS patients receiving intramuscular interferon beta-1a (IM IFNβ-1a) were screened for attention problems with four well-validated, reliable, standardized neurocognitive measures sensitive to attention impairment. Those scoring at least 1 standard deviation below normative expectations on at least two of the measures were eligible for continued participation. Participants with normal values on all physical screening measures were randomized to one of two groups: continued IM IFNβ-1a...