A case of progressive multifocal leukoencephalopathy in a lupus patient treated with belimumab.

Belimumab is a monoclonal antibody against soluble B-lymphocyte stimulator, an essential growth factor for B-cell maturation and activation, which was approved by the US FDA in 2011 for patients with active autoantibody-positive systemic lupus erythematosus (SLE) who have failed standard treatment. Here we present the case of a 40-year-old woman with SLE diagnosed with progressive multifocal leukoencephalopathy (PML) on belimumab. After a total of 10 infusions of belimumab, from August 2012 through April 2013, in April 2013 she developed progressive neurologic decline with episodic dystonia and autonomic symptoms. Her imaging showed multifocal, confluent regions of T2 hyperintensity in the white matter bilaterally, and CSF JCV PCR returned positive. Based on the patient's clinically mild SLE and the timing of symptom onset, belimumab likely played a key role in the development of PML. Trials of belimumab for other autoimmune diseases are ongoing; as applications for this novel drug broaden, careful monitoring for this potentially fatal adverse effect is warranted.

Cerebral perfusion-CT patterns following seizure.

BACKGROUND: Cerebral perfusion-CT (PCT) is commonly used to image patients with suspected stroke, but PCT may also be useful in detecting abnormalities following seizure. METHODS: We retrospectively identified patients who presented to our stroke center between 2000 and 2008 with acute, transient neurological deficits because of seizure and received PCT imaging within 72 h. We compared the group of seizure patients with abnormal post-ictal PCT to a group of seizure patients with normal post-ictal PCT. Patients were excluded from analysis if the seizure occurred secondary to an acute process known to alter cerebral perfusion. RESULTS: Of 27 patients with acute post-ictal neurological deficits, PCT was abnormal in 10 (37%) and normal in 17 (63%). The most common post-ictal perfusion abnormality, seen in eight of 10 patients, was focal hypoperfusion, with prolonged mean transit time (MTT) and decreased cerebral blood flow and cerebral blood volume, in a cortical ribbon pattern, multi-lobar or holo-hemispheric distribution, sparing the basal ganglia. CT Angiography (CTA) showed no corresponding large vessel pathology. Two other PCT abnormalities--focal hyperperfusion and an isolated prolonged MTT--were also observed in single patients. Imaging within 2 h after seizure termination was significantly associated with finding a post-ictal PCT abnormality (P < 0.039). CONCLUSIONS: Post-ictal cerebral PCT abnormalities are relatively common in patients early after seizure. When PCT abnormalities occur in atypical vascular distributions--and the CTA shows no corresponding large vessel occlusions--seizure should be considered as a diagnostic possibility prior to giving acute stroke therapy.

Autosomal dominant Kufs' disease: a cause of early onset dementia.

Kufs' disease is the rare, adult-onset form of the neuronal ceroid-lipofuscinoses (NCL). Two clinical Kufs' phenotypes have been described, one featuring generalized tonic-clonic seizures and the other characterized by dementia. Autosomal dominant inheritance of Kufs' disease has been reported for only two families. The genetic and molecular defects underlying Kufs' disease are unknown. We report a third family with apparent autosomal dominant Kufs' disease in a family of English ancestry. Ten individuals (five men, five women) have been affected over five generations. Age of onset typically is in the fourth decade of life and is heralded by seizures. Clinical and neuropsychological assessments in several affected individuals, however, confirm the presence of dementia and follow-up evaluations suggest that dementia is the primary disabling feature of the illness. Motor abnormalities also are frequent. Neuropathological examination (three cases) documents the presence of neuronal lipopigment accumulation consistent with NCL. The combination of dementia and seizures in this and two other reported families with autosomal dominant Kufs' disease suggest that this entity represents a distinctive clinicopathological entity. Dementia is prominent but is almost always associated with generalized seizures and motoric disturbances early in the disease course. Kufs' disease should be considered in the differential diagnosis of early onset, atypical dementia.

A randomized trial of hypothesis-driven vs screening neurologic examination.

OBJECTIVE: We hypothesized that trainees would perform better using a hypothesis-driven rather than a traditional screening approach to the neurologic examination. METHODS: We randomly assigned 16 medical students to perform screening examinations of all major aspects of neurologic function or hypothesis-driven examinations focused on aspects suggested by the history. Each student examined 4 patients, 2 of whom had focal deficits. Outcomes of interest were the correct identification of patients with focal deficits, number of specific deficits detected, and examination duration. Outcomes were assessed by an investigator blinded to group assignments. The McNemar test was used to compare the sensitivity and specificity of the 2 examination methods. RESULTS: Sensitivity was higher with hypothesis-driven examinations than with screening examinations (78% vs 56%; p = 0.046), although specificity was lower (71% vs 100%; p = 0.046). The hypothesis-driven group identified 61% of specific examination abnormalities, whereas the screening group identified 53% (p = 0.008). Median examination duration was 1 minute shorter in the hypothesis-driven group (7.0 minutes vs 8.0 minutes; p = 0.13). CONCLUSIONS: In this randomized trial comparing 2 methods of neurologic examination, a hypothesis-driven approach resulted in greater sensitivity and a trend toward faster examinations, at the cost of lower specificity, compared with the traditional screening approach. Our findings suggest that a hypothesis-driven approach may be superior when the history is concerning for an acute focal neurologic process.

Acid steatocrit: a simple, rapid gravimetric method to determine steatorrhea.

OBJECTIVES: The detection and evaluation of steatorrhea in a rapid, quantitative fashion are clinically needed in patients with suspected steatorrhea. Our aim was to evaluate the acid steatocrit method, on random spot stools in adults with and without steatorrhea, relative to the qualitative (microscopic) and quantitative assessments for fecal fat. METHODS: Stool samples were collected 72 h after a diet of 100 g of fat per day and randomly from 15 healthy controls, 14 patients with chronic pancreatitis, and seven patients with small bowel disease. All stools had quantitative, qualitative, and acid steatocrit analyses performed for fecal fat. RESULTS: The sensitivity and specificity for the detection of steatorrhea by the spot stool qualitative fecal fat were 78 and 70%, respectively. The spot stool acid steatocrit correlated linearly with the 72-h stool quantitative fecal fat (g/24 h), r = 0.761 and p < 0.001. The acid steatocrit on random spot stools, compared with the 72-h stool quantitative fecal fat, revealed a sensitivity of 100%, a specificity of 95%, and a positive predictive value of 90% for the detection of steatorrhea. It also estimated the quantitative fecal fat. CONCLUSIONS: The acid steatocrit can be performed accurately on random spot stools and can be used to detect the presence of steatorrhea and estimate the quantitative fecal fat. This assay can be done with readily available equipment for rapid evaluation. Use of a spot stool sample simplifies the acid steatocrit, further improving on the practicality of this test. This study also confirms the clinical usefulness of this simplified method to detect steatorrhea.

Evaluation of carotid stenosis using CT angiography in the initial evaluation of stroke and TIA.

BACKGROUND: Imaging of the carotid arteries is important for the evaluation of patients with ischemic stroke or TIA. CT angiography (CTA) of the head and neck is readily available and can be part of the routine imaging of stroke patients. To evaluate the accuracy of CTA, the authors compared the degree of stenosis found using CTA with digital subtraction angiography (DSA) in consecutive patients during a 3-year period. METHODS: The authors included all patients with interpretable CTA and DSA of the cervical carotid arteries from April 2000 to November 2002 at a single academic medical center. This yielded a total of 81 vessels. Stenosis on CTA of the internal carotid artery was measured in the axial plane at the point of maximum stenosis and referenced to the distal cervical internal carotid by two blinded readers. Two blinded readers measured stenosis from the DSA using the North American Symptomatic Carotid Endarterectomy Trial method. RESULTS: Using a 70% cutoff value for stenosis, CTA and DSA were in agreement in 78 of 81 (96%; 95% CI, 90 to 99%) vessels. CTA was 100% sensitive (n = 5) and 63% specific (95% CI, 25 to 88%), and the negative predictive value of a CTA demonstrating <70% stenosis was 100% (n = 73). CONCLUSIONS: In this consecutive series of patients with CT angiography of the neck and digital subtraction angiography, the authors found that CT angiography has a high sensitivity and high negative predictive value for carotid disease. CT angiography appears to be an excellent screening test for internal carotid artery stenosis, and the authors advocate its use for the initial imaging of patients with suspected stroke or TIA.