Enabling Anyone to Translate Clinically Relevant Ideas to Therapies.

How do we inspire new ideas that could lead to potential treatments for rare or neglected diseases, and allow for serendipity that could help to catalyze them? How many potentially good ideas are lost because they are never tested? What if those ideas could have lead to new therapeutic approaches and major healthcare advances? If a clinician or anyone for that matter, has a new idea they want to test to develop a molecule or therapeutic that they could translate to the clinic, how would they do it without a laboratory or funding? These are not idle theoretical questions but addressing them could have potentially huge economic implications for nations. If we fail to capture the diversity of ideas and test them we may also lose out on the next blockbuster treatments. Many of those involved in the process of ideation may be discouraged and simply not know where to go. We try to address these questions and describe how there are options to raising funding, how even small scale investments can foster preclinical or clinical translation, and how there are several approaches to outsourcing the experiments, whether to collaborators or commercial enterprises. While these are not new or far from complete solutions, they are first steps that can be taken by virtually anyone while we work on other solutions to build a more concrete structure for the "idea-hypothesis testing-proof of concept-translation-breakthrough pathway".

Calcified parenchymal central nervous system cysticercosis and clinical outcomes in epilepsy.

OBJECTIVE: This study aimed to compare clinical outcomes including seizure frequency and psychiatric symptoms between patients with epilepsy with neuroimaging evidence of past brain parenchymal neurocysticercosis infection, patients with other structural brain lesions, and patients without structural neuroimaging abnormalities. MATERIAL AND METHODS: The study included retrospective cross-sectional analysis of all patients treated for epilepsy in a community-based adult neurology clinic during a three-month period. RESULTS: A total of 160 patients were included in the analysis, including 63 with neuroimaging findings consistent with past parenchymal neurocysticercosis infection, 55 with structurally normal brain neuroimaging studies, and 42 with other structural brain lesions. No significant differences were detected between groups for either seizure freedom (46.03%, 50.91%, and 47.62%, respectively; p=0.944) or mean seizure frequency per month (mean=2.50, S.D.=8.1; mean=4.83, S.D.=17.64; mean=8.55, S.D.=27.31, respectively; p=0.267). Self-reported depressive symptoms were more prevalent in those with parenchymal neurocysticercosis than in the other groups (p=0.003). No significant differences were detected for prevalence of self-reported anxiety or psychotic symptoms. CONCLUSIONS: Calcified parenchymal neurocysticercosis results in refractory epilepsy about as often as other structural brain lesions. Depressive symptoms may be more common among those with epilepsy and calcified parenchymal neurocysticercosis; consequently, screening for depression may be indicated in this population.

Whole brain CT perfusion deficits using 320-detector-row CT scanner in TIA patients are associated with ABCD2 score.

BACKGROUND: Transient ischemic attacks (TIA) are cerebral ischemic events without infarction. The uses of CT perfusion (CTP) techniques such as cerebral blood volume (CBV), time to peak (TTP), mean transit time (MTT) and cerebral blood flow (CBF) provide real time data about ischemia. It has been shown that CTP changes occur in less sensitive CTP scanners in patients with TIA. Larger detector row CTP (whole brain perfusion studies) may show that CTP abnormalities are more prevalent than previously noted. It is also unclear if these changes are associated with TIA severity. OBJECTIVE: To demonstrate that TIA patients are associated with perfusion deficits using whole brain 320-detector-row CT perfusion, and to determine an association between ABCD2 score and perfusion deficit using whole brain perfusion. METHODS: We retrospectively reviewed all TIA patients for CTP deficits from 2008-2010. Perfusion imaging was reviewed at admission; and it was determined if a perfusion deficit was present along with vascular territory involved. RESULTS: Of 364 TIA patients, 62 patients had CTP deficits. The largest group of patients had MCA territory involved with 48 of 62 patients (77.42%). The most common perfusion abnormality was increased TTP with 46 patients (74.19%). The ABCD2 score was reviewed in association with perfusion deficit. Increased age >60, severe hypertension (>180/100 mmHg), patients with speech abnormalities, and duration of symptoms >10 min were associated with a perfusion deficit but history of diabetes or minimal/moderate hypertension (140/90-179/99 mmHg) was not. There was no association between motor deficit and perfusion abnormality. CONCLUSION: Perfusion deficits are found in TIA patients using whole brain CTP and associated with components of the ABCD2 score.

Cerebrovascular risk factors and brain microstructural abnormalities on diffusion tensor images in HIV-infected individuals.

HIV-associated neurocognitive disorder remains prevalent in HIV-infected individuals despite effective antiretroviral therapy. As these individuals age, comorbid cerebrovascular disease will likely impact cognitive function. Effective tools to study this impact are needed. This study used diffusion tensor imaging (DTI) to characterize brain microstructural changes in HIV-infected individuals with and without cerebrovascular risk factors. Diffusion-weighted MRIs were obtained in 22 HIV-infected subjects aged 50 years or older (mean age = 58 years, standard deviation = 6 years; 19 males, three females). Tensors were calculated to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps. Statistical comparisons accounting for multiple comparisons were made between groups with and without cerebrovascular risk factors. Abnormal glucose metabolism (i.e., impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus) was associated with significantly higher MD (false discovery rate (FDR) critical p value = 0.008) and lower FA (FDR critical p value = 0.002) in the caudate and lower FA in the hippocampus (FDR critical p value = 0.004). Pearson correlations were performed between DTI measures in the caudate and hippocampus and age- and education-adjusted composite scores of global cognitive function, memory, and psychomotor speed. There were no detectable correlations between the neuroimaging measures and measures of cognition. In summary, we demonstrate that brain microstructural abnormalities are associated with abnormal glucose metabolism in the caudate and hippocampus of HIV-infected individuals. Deep gray matter structures and the hippocampus may be vulnerable in subjects with comorbid abnormal glucose metabolism, but our results should be confirmed in further studies.

Corrigendum to "Gender and Ethnicity Based Differences in Clinical and Laboratory Features of Myasthenia Gravis".

[This corrects the article DOI: 10.1155/2015/197893.].

Language preference and development of dementia among bilingual individuals.

In bilingual individuals, regression to a primary language may be associated with development of cognitive impairment and increased risk for development of dementia. This report describes two bilingual patients who presented with early symptoms of dementia after regression to their primary language. The results of this study may help clinicians identify aging bilingual patients who are beginning to develop cognitive impairment or dementia and suggest that further studies on the long term cognitive effects of bilingualism and interactions with the aging process are indicated.

Extracellular binding of indinavir to matrix metalloproteinase-2 and the alpha-7-nicotinic acetylcholine receptor: implications for use in cancer treatment.

INTRODUCTION: Results from recent studies have suggested a role for protease inhibitors in altering mechanisms involved in the initiation and proliferation of cancer cells. One such inhibitor, indinavir, may act as an anti-cancer agent by modulating the alpha-7-nicotinic acetylcholine receptor, which is a pro-carcinogenic protein that has been researched in conjunction with nicotine in lung cancer development. In our study, we compare indinavir's binding affinity towards α7-nAchR and MMP-2, another promoter of malignancy, to determine what extracellular effects the drug has before being internalized to inhibit HIV-1 protease. METHODS: A computer program, PyRx, was used to compare indinavir's binding affinity with digital models for α7-nAchR, MMP-2 and HIV-1 protease, which were then compared to the results of in vitro binding assays for these targets. RESULTS: PyRx testing predicted the highest binding affinity values for indinavir to MMP-2 (mean = 8.77 kcal/mol, S.D. = 0.29), followed by the α7-nAchR (mean = 8.53 kcal/mol, S.D. = 0.15) and HIV-1 protease (mean = 7.5 kcal/mol, S.D. = 0.44). In vitro, indinavir's mean percent inhibition of control values were 103.2 for HIV-1 protease, 5.3 for MMP-2, and 7.7 for the α7-nAchR. CONCLUSIONS: Binding affinity values for indinavir to MMP-2 and α7-nAchR were not significantly different. Using PyRx to predict affinity compared with in vitro testing did not yield comparable results. However, indinavir was shown to slightly inhibit both α7-nAchR and MMP-2, which may have ramifications in the drug's delivery to the intracellularly located HIV-1 protease.

Aging exacerbates extrapyramidal motor signs in the era of highly active antiretroviral therapy.

The phenotype of human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) in the developed world has changed with the broad institution of highly active antiretroviral therapy (HAART) and with aging of the HIV+ population. Extrapyramidal motor signs were a prominent feature of HAND as defined in the early stages of the epidemic but has not been reevaluated in the era of HAART. Moreover, the contribution of aging to extrapyramidal motor signs in the context of HIV remains undefined. We examined these questions among the 229 HIV+ participants in the Hawaii Aging with HIV Cohort compared to age-, gender-, and ethnicity-matched HIV-negative controls. Extrapyramidal motor signs were quantified using the motor exam of the Unified Parkinson's Disease Rating Scale (UPDRSmotor) and compared to concurrent neuropsychological and clinical cognitive diagnostic categorization. The mean UPDRSmotor score increased with older age (1.68 versus 3.35; P<.001) and with HIV status (1.18 versus 3.56; P<.001). Age group (P=.024), HIV status (P<.001), and the interaction between age and HIV (P=.026) were significantly associated with UPDRSmotor score. Among HIV+ patients, the mean UPDRSmotor score increased with worsening cognitive diagnostic category (P<.001) where it was 2.06 (2.31) in normal cognition (n=110), 3.21 (3.48) in minor cognitive motor disorder (MCMD) (n=84), and 5.72 (5.01) in HIV-associated dementia (HAD) (n=37). We conclude that extrapyramidal motor signs are increased in HIV in the era of HAART and that the impact of HIV on extrapyramidal motor signs is exacerbated by aging. These results highlight the importance of a careful neurological examination in the evaluation of HIV patients.

Positron emission tomography facilitates diagnosis of early-onset Alzheimer's disease.

BACKGROUND: Clinical positron emission tomography (PET) may help in the evaluation of presenile patients with memory complaints for the presence of Alzheimer's disease (AD). METHODS: Clinical PET scans from 27 patients with clinically probable AD and early ages of onset (<65 years) were compared to PET scans from 27 age-matched controls presenting with memory complaints, but without dementia or mild cognitive impairment. RESULTS: Compared to controls, the AD patients had significant frontal, temporal and parietal hypometabolism bilaterally, and AD diagnosis correlated with left temporal and right temporoparietal hypometabolism. The sensitivity of temporoparietal hypometabolism for AD was 92.6%, the specificity 85.2%. CONCLUSION: Clinical PET imaging helps distinguish early-onset AD from patients with memory complaints not meeting criteria for dementia or mild cognitive impairment.

Cortical atrophy and white matter hyperintensities in HIV: the Hawaii Aging with HIV Cohort Study.

BACKGROUND: As many human immunodeficiency virus (HIV)-seropositive individuals are now living longer after infection because of highly active antiretroviral therapy, aging-related manifestations of cerebral small-vessel ischemic vascular disease, such as brain white matter hyperintensities (WMHs), are becoming increasingly important in this population. GOALS: This study was designed to determine the relationship between WMHs and cortical volumes in HIV-seropositive individuals. MATERIALS AND METHODS: Voxel-based morphometry was used to compare cortical volumes among 62 HIV-seropositive individuals participating in the Hawaii Aging with HIV Cohort Study, 30 with moderate WMHs and 32 with minimal or no WMHs. RESULTS: Presence of moderate WMHs was associated with decreased cortical volumes in the frontal lobes bilaterally. CONCLUSION: These findings suggest that age-related WMHs are associated with reduced frontal gray matter volumes in HIV-seropositive individuals, supporting the hypothesis that the frontal lobes may have greater susceptibility to the effects of small-vessel ischemic vascular disease.

Accuracy of the clinical evaluation for frontotemporal dementia.

BACKGROUND: Without a definitive clinical test, the early diagnosis of frontotemporal dementia (FTD) can be difficult. OBJECTIVE: To evaluate the accuracy of the clinical evaluation for FTD. DESIGN: Retrospective assessment of consensus criteria for FTD, neuropsychological measures, magnetic resonance images, and single-photon emission computed tomography/positron emission tomography (SPECT/PET) scans at baseline compared with a standard of subsequent clinical diagnosis after follow-up and reevaluation to year 2. SETTING: University hospital. PATIENTS: A total of 134 patients referred for clinical evaluation of suspected FTD. These patients had 1 or more core or supportive features of FTD in the absence of another etiology on initial assessment. MAIN OUTCOME MEASURES: Sensitivities, specificities, and predictive values of consensus criteria for FTD, magnetic resonance images, and SPECT/PET scans at initial assessment. RESULTS: The sensitivities and specificities for the diagnosis of FTD were 36.5% and 100.0% for consensus criteria, 63.5% and 70.4% for magnetic resonance images, and 90.5% and 74.6% for SPECT/PET scans, respectively. With a previous prevalence of nearly 50% for FTD, the positive predictive value was greatest for consensus criteria (100.0%), and the negative predictive value was greatest for SPECT/PET (89.8%). The initial neuropsychological results did not distinguish FTD, but the pattern of progression (worse naming and executive functions and preserved constructional ability) helped establish the diagnosis at year 2. CONCLUSIONS: Consensus criteria for FTD and neuropsychological measures lacked sensitivity for FTD; however, neuroimaging, particularly functional brain studies, greatly increased the sensitivity of detecting FTD. The clinical diagnosis of FTD needs to combine neuropsychiatric features with SPECT or PET findings while following the changes on neuropsychological tests.

Cognitive differences between early- and late-onset Alzheimer's disease.

Although neuropathologic studies showed that early-onset Alzheimer's disease (EAD) and "senile dementia" were indistinguishable, clinical studies suggested that EAD and late-onset Alzheimer's disease (LAD) were cognitively distinct. We sought to investigate whether EAD and LAD are cognitively different by comparing patients at the extremes of the ages of onset in order to maximize features that might separate them. We compared 44 men with EAD (age of onset less than 65 years) with 44 men with LAD (age of onset 84 years or older) on an intake cognitive screening examination on initial presentation. The EAD and LAD groups did not differ on dementia or most cognitive variables. Compared with EAD, the LAD group had worse verbal fluency and motor-executive functions. These differences disappeared when age differences were taken into account. We conclude that Alzheimer's disease is a clinically heterogeneous disorder whose manifestations can vary with age of onset. These differences indicate age-related vulnerabilities in this disease.

Smoking history and Alzheimer's disease risk in a community-based clinic population.

BACKGROUND: The relationship between cigarette smoking and development of Alzheimer's disease (AD) is not fully determined, and previous reports disagree, with some studies suggesting an increased relative risk and others a decreased odds ratio. Consequently, we wanted to determine if the prevalence of past cigarette smoking observed in a community-based clinic sample of patients with AD would be more consistent with the expected value obtained from a model using either an increased relative risk or a decreased odds ratio to estimate the effect of smoking on development of AD. MATERIALS AND METHODS: Retrospective cross-sectional analysis of all patients treated for AD in a community-based Neurology Clinic during a 2-year period. Estimates of expected past smoking prevalence were calculated based on published values for either an increased relative risk or a decreased odds ratio and compared to the past smoking prevalence observed in the clinic sample. RESULTS: The observed past smoking prevalence in the clinic population was 29.17%. The expected past smoking prevalence calculated using the increased relative risk was 30.07% (95% confidence interval [CI] = 27.67-32.32%), and using the decreased odds ratio was 12.54% (95% CI = 6.32-24.81%). CONCLUSION: The observed past smoking prevalence among the patients being treated for AD in a community-based clinic falls within the expected 95% CI for the increased relative risk model and outside of the expected 95% CI for the decreased odds ratio model. These results support the contention that the relationship between cigarette smoking and development of AD is the best characterized by an increased relative risk.

Headaches More Common among Epilepsy Sufferers with Neurocysticercosis than Other Structural Brain Lesions.

Neurocysticercosis is a leading cause of seizures and epilepsy in the developing world. Cysticercosis is endemic in many regions of Central and South America, sub-Saharan Africa, India, and Asia. Neurocysticercosis is of emerging importance because globalization has increased travel between Hawai'i and disease-endemic areas. Headache and epilepsy are two of the most common complications of neurocysticercosis infection. Currently, it is not known if epilepsy patients with neurocysticercosis are more likely to have headaches than those with other structural brain lesions or those with no structural brain abnormalities. This study was designed to investigate whether epilepsy patients with neurocysticercosis report co-morbid headaches more frequently than those with other or with no structural brain lesions. A retrospective cross-sectional study of all patients treated at a community based neurology clinic for epilepsy during a three-month period was performed. One-hundred sixty patients were included in the analytical study. Co-morbid headaches were more commonly present among those with neurocysticercosis (40%) than those with other structural lesions and those with no structural brain abnormalities (19% and 22%, respectively; P = .031). Headache frequency among those reporting co-morbid headaches did not differ significantly between the groups. Prevalence of co-morbid headaches is greater among epilepsy patients with neurocysticercosis than those with other structural brain lesions or no structural brain abnormality. Epilepsy patients with neurocysticercosis may be especially vulnerable to development of headaches and a thorough headache history should be obtained to help screen for affected individuals.

α7-Nicotinic acetylcholine receptor inhibition by indinavir: implications for cognitive dysfunction in treated HIV disease.

OBJECTIVE: The study set out to determine if the HIV protease inhibitor, indinavir, alters responsiveness of α7-nicotinic acetylcholine receptors to acetylcholine. DESIGN: Treatment with HAART has dramatically reduced development of HIV-associated dementia and more severe forms of cognitive impairment. However, many individuals continue to experience cognitive decline of uncertain cause. Previous studies have failed to demonstrate significant alterations of functional brain connectivity, structural brain changes, or changes in cerebral blood flow sufficient to explain cognitive decline in virally suppressed individuals. This suggests that the mechanisms underlying development and progression of cognitive problems likely occurs at a micro rather than macro level, such as disruptions in neurotransmitter system signaling. MATERIALS AND METHODS: Indinavir's effects on α7-nicotinic acetylcholine receptor activity was tested using a ScreenPatch IonWorks Barracuda-based assay in a mammalian cell model. RESULTS: At low concentrations (0.0003-10 µmol/l) indinavir acts as a positive allosteric modulator (EC50 = 0.021 µmol/l), whereas at concentrations greater than 10 µmol/l (30-100 µmol/l) indinavir acts as an inhibitor of the α7-nicotinic acetylcholine receptor. CONCLUSION: At concentrations greater than 10 µmol/l indinavir reduces synaptic transmission in the acetylcholine neurotransmitter system, which could possibly contribute to cognitive dysfunction. These results suggest that further experiments should be considered to assess whether patients might benefit from treatment with cholinesterase inhibitors that counteract the effects of indinavir.

Outbreak of pertussis among healthcare workers in a hospital surgical unit.

BACKGROUND: In September 1999, a pertussis outbreak was detected among surgical staff of a 138-bed community hospital. Patients were exposed to Bordetella pertussis during the 3-month outbreak period. OBJECTIVE: To describe the outbreak among surgical staff, to evaluate implemented control measures, and to determine whether nosocomial transmission occurred. METHODS: Clinical pertussis was defined as acute cough illness with a duration of 14 days or more without another apparent cause; persons with positive culture, PCR, or serologic test results were defined as having laboratory-confirmed pertussis. Surgical healthcare workers (HCWs) were interviewed regarding pertussis symptoms, and specimens were obtained for laboratory analysis. Patients exposed to B. pertussis during an ill staff member's 3-week infectious period were interviewed by phone to determine the extent of nosocomial spread. PARTICIPANTS: A total of 53 HCWs assigned to the surgical unit and 146 exposed patients. HCWs with pertussis were defined as case subjects; HCWs without pertussis were defined as non-case subjects. RESULTS: Twelve (23%) of 53 HCWs had clinical pertussis; 6 cases were laboratory confirmed. The median cough duration in the 12 case subjects was 27 days (range, 20-120 days); 10 (83%) had paroxysms. Eleven (92%) of 12 case subjects and 28 (86%) of 41 non-case subjects received antibiotic treatment or prophylaxis. Seven case subjects (58%) reported they always wore a mask when near patients. Of 146 patients potentially exposed to pertussis from the 12 case subjects, 120 (82%) were interviewed; none reported a pertussis-like illness. CONCLUSIONS: Surgical staff transmitted B. pertussis among themselves; self-reported data suggests that these HCWs did not transmit B. pertussis to their patients, likely because of mask use, cough etiquette, and limited face-to-face contact. Control measures might have helped limit the outbreak once pertussis was recognized.

Frontotemporal dementia-like phenotypes associated with presenilin-1 mutations.

Frontal behavioral changes may be the presenting features of single-photon emission tomography (presenilin-1 [PS-1]) mutations, the most common cause of familial Alzheimer's disease (AD). The authors describe a PS-1 (M233L) mutation with the features of frontotemporal dementia (FTD) and review the literature. PS-1 mutations may produce FTD-like phenotypes with the neuropathology of AD. Some PS-1 mutations have additional Pick's bodies, a neuropathological marker of FTD, and a report of a PS-1 (G183V) mutation found Pick's bodies without amyloid plaques. The patient and the literature suggest that PS-1 mutations result in an overlapping continuum of the clinical and neuropathological features of AD and FTD. In PS-1 mutations, the expression of AD or FTD may depend on the degree of loss of function of the PS-1 gene and the resultant tau pathophysiology.

Topographic congruence of calcified parenchymal neurocysticercosis and other structural brain lesions with epileptiform activity.

INTRODUCTION: Calcified parenchymal neurocysticercosis (NCC) lesions are commonly detected in many individuals with refractory epilepsy. However, the relationship between these lesions and epilepsy is not fully determined. We sought to determine if calcified parenchymal NCC demonstrated topographic congruence with epileptiform activity in refractory epilepsy patients. Additional patients with other structural brain lesions were included for comparison. SUBJECTS AND METHODS: Retrospective cross-sectional analysis of all patients treated at a community-based neurology clinic for refractory epilepsy during a 3-month period and with structural brain lesions detected by neuroimaging studies. RESULTS: A total of 105 patients were included in the study, including 63 with calcified parenchymal NCC lesions and 42 with other structural brain lesions. No significant relationship was detected between hemispheric localization of calcified parenchymal NCC lesions and epileptiform activity. For those with other structural brain lesions, the hemispheric localization was significantly related to the side of epileptiform activity (Chi-square = 11.13, P = 0.025). In addition, logistic regression models showed that those with right-sided non-NCC lesions were more likely to have right-sided epileptiform activity (odds ratio = 4.36, 95% confidence interval [CI] =1.16-16.31, P = 0.029), and those with left-sided non-NCC lesions were more likely to have left-sided epileptiform activity (odds ratio = 7.60, 95% CI = 1.89-30.49, P = 0.004). CONCLUSION: The lack of correlation between the side of calcified parenchymal NCC lesions and the side of the epileptiform activity suggests that these lesions may be incidental findings in many patients.

Lower Frequency of co-Morbid Medical Disorders Related to Poor Impulse Control in Parkinson's than Alzheimer's Disease.

Parkinson's disease is associated with progressive degeneration of mesolimbic dopaminergic neurons that are involved in reward-based behavior learning, including rewarding effects of food consumption and drugs of abuse. The importance of this pathway in development of addictive behaviors led us to hypothesize that medical disorders related to poor impulse control may occur less frequently among patients with Parkinson's disease than those with other progressive neurodegenerative disorders such as Alzheimer's disease. Retrospective cross-sectional study of all patients treated for Parkinson's disease and Alzheimer's disease in a community based clinic during a two-year period. Associations were summarized using odds ratios (OR) and 95% confidence intervals (95% CI) estimated from logistic regression models, adjusted for differences in gender distribution between the groups. A total of 106 patients with Parkinson's disease and 72 patients with Alzheimer's disease were included. Patients with Parkinson's disease were less likely to have either past substance use (adjusted OR = 0.035, 95% CI = 0.009 - 0.130) or presence of co-morbid medical conditions related to poor dietary choices (adjusted OR = 0.157, 95% CI = 0.062 - 0.397). Co-morbid medical conditions related to poor impulse control occur less frequently among those with Parkinson's disease than those with Alzheimer's disease. These findings are consistent with dysfunction of dopamine dependent pathways involved in addiction during the presymptomatic phase of Parkinson's disease and support a biological basis for addiction.

CNS Vasculitis Associated with Waldenström Macroglobulinemia.

Waldenström macroglobulinemia (WM) is an indolent B cell lymphoproliferative disorder with monoclonal IgM secretion. We present a patient with WM who presented with multifocal acute cortical ischemic strokes and was found to have central nervous system (CNS) vasculitis. Workup was negative for cryoglobulins and hyperviscosity syndrome. Immunosuppression with intravenous steroids and cyclophosphamide stabilized the patient's mental status and neurologic deficits. On followup over 7 years, patient gained independence from walking aids and experienced no recurrences of CNS vasculitis. To our knowledge, CNS vasculitis in a WM patient, in the absence of cryoglobulins, has not been reported. Immunosuppression is the preferred treatment.