Objective To examine rates of decline in individuals at risk for Huntington disease (HD).Methods 106 individuals at risk for HD completed a battery of neurocognitive, psychomotor and oculomotor tasks at two visits, approximately 2.5 years apart. Participants were classified as: (1) without the CAG expansion (normal controls, NC; n=68) or (2) with the CAG expansion (CAG+; n=38). The CAG+ group was further subdivided into those near to (near; n=19) or far from (far; n=19) their estimated age of onset. Longitudinal performance in the CAG+ group was evaluated with a repeated measures model with two main effects (time to onset, visit) and their interaction. Analysis of covariance was employed to detect differences in longitudinal performance in the three groups (NC, near and far).Results In the CAG+, the interaction term was significant (p <= 0.02) for four measures (movement time, alternate button tapping, variability of latency for a memory guided task and percentage of errors for a more complex memory guided task), suggesting the rate of decline was more rapid as subjects approached onset. Longitudinal progression in the three groups differed for several variables (p<0.05). In most, the near group had significantly faster progression than NC; however, comparisons of the NC and far groups were less consistent.Conclusions Different patterns of progression were observed during the prediagnostic period. For some measures, CAG+ subjects closer to estimated onset showed a more rapid decline while for other measures the CAG+ group had a constant rate of decline throughout the prediagnostic period that was more rapid than in NC.

The objective of this study was to evaluate visual scanning strategies in carriers of the Huntington disease (HD) gene expansion and to test whether there is an association between measures of visual scanning and cognitive performance. The study sample included control (NC, n = 23), prediagnostic (PDHD, n = 21), and subjects recently diagnosed with HD (HD, n = 19). All participants completed a uniform clinical evaluation that included examination by neurologist and molecular testing. Eye movements were recorded during completion of the Digit Symbol Subscale (DS) test. Quantitative measures of the subject's visual scanning were evaluated using joint analysis of eye movements and performance on the DS test. All participants employed a simple visual scanning strategy when completing the DS test. There was a significant group effect and a linear trend of decreasing frequency and regularity of visual scanning from NC to PDHD to HD. The performance of all groups improved slightly and in a parallel fashion across the duration of the DS test. There was a strong correlation between visual scanning measures and the DS cognitive scores. While all individuals employed a similar visual scanning strategy, the visual scanning measures grew progressively worse from NC to PDHD to HD. The deficits in visual scanning accounted, at least in part, for the decrease in the DS score. © 2008 Movement Disorder Society

Disturbances of visual perception frequently accompany neurodegenerative disorders but have been little studied in Huntington's disease (HD) gene carriers. We used psychophysical tests to assess visual perception among individuals in the prediagnostic and early stages of HD. The sample comprised four groups, which included 201 nongene carriers (NG), 32 prediagnostic gene carriers with minimal neurological abnormalities (PD1); 20 prediagnostic gene carriers with moderate neurological abnormalities (PD2), and 36 gene carriers with diagnosed HD. Contrast sensitivity for stationary and moving sinusoidal gratings, and tests of form and motion discrimination, were used to probe different visual pathways. Patients with HD showed impaired contrast sensitivity for moving gratings. For one of the three contrast sensitivity tests, the prediagnostic gene carriers with greater neurological abnormality (PD2) also had impaired performance as compared with NG. These findings suggest that early stage HD disrupts visual functions associated with the magnocellular pathway. However, these changes are only observed in individuals diagnosed with HD or who are in the more symptomatic stages of prediagnostic HD.

Dementia screening batteries often fall short on measures of executive functioning. The Weigl Color Form Sorting Test (WCFST) is a candidate for inclusion in such batteries, but can be insensitive to mild disturbance. The WCFST consists of 12 colored geometric shapes and requires the patient to sort the pieces by color or form, and then shift to the other sorting principle unassisted. We created a modified version of the WCFST (the Weigl-R) with increased conceptual complexity by adding two stimulus dimensions (texture and central shapes). The range of scores was also increased by adding the extent of examiner assistance required to achieve a correct sort, ability to verbalize conceptual strategy, and number of perseverations. We administered the Weigl-R to a group of 30 patients with mixed dementias, 34 adults with cognitive impairment without dementia, and 21 healthy controls. The new measure discriminated well between healthy controls and older adults with either cognitive impairment without dementia, or dementia. The Weigl-R may be a useful adjunct to brief dementia batteries but requires further validation.

Longitudinal studies of neurocognitive function in prediagnosis Huntington disease (pre-HD) have been few, and duration of follow-up has been brief. In this study, 155 individuals at-risk for HD completed a battery of cognitive and motor tasks at two study visits approximately 10 years apart. Participants were classified as: (1) at-risk, without the CAG expansion (healthy controls, NC; n = 112), or (2) CAG expanded (CAG+; n = 43). To examine the rate of decline at different stages of the pre-HD period, participants in the CAG+ group were further characterized as converters (i.e., individuals who developed manifest HD over the course of the study; n = 21) or nonconverters (n = 22), and their performances were compared. The CAG+ group exhibited faster rates of neurocognitive decline over the course of the study, relative to the NC group. In addition, more rapid decline was associated with closer proximity to estimated age of disease onset in the CAG+ group. Faster rates of motor and psychomotor decline were observed in the CAG+ converter group, relative to the nonconverters. These findings suggest that neurocognitive decline in pre-HD, particularly in motor and psychomotor domains, begins insidiously and accelerates as individuals approach disease onset.

ObjectiveTo characterize neurocognitive signs of disease progression in prediagnosis and early Huntington disease (HD) and compare the sensitivity of 2 disease staging classification schemes for detecting these signs. MethodsThree hundred and six individuals at-risk for or recently diagnosed with HD completed the Unified Huntington's Disease Rating Scale, genetic testing, and a neurocognitive battery. Two schemes were used to estimate latency to onset of disease. One was based on genetic information (CAG repeat length) and the other was based on the extent of motor signs. Effect sizes were compared to assess the relative sensitivity of the 2 schemes for detecting signs of disease progression. ResultsCAG-expanded participants far from estimated diagnosis performed similarly to controls, whereas those near to estimated diagnosis were impaired relative to controls. Overall, the method employing genetic information yielded larger effect sizes than the motor scheme, particularly for strategic and executive function measures; the motor scheme resulted in a larger effect size for a measure of motor/psychomotor function. ConclusionsNeurocognitive function is not uniformly affected in prediagnosis and early HD; individuals near to their estimated age of diagnosis have cognitive signs similar to HD, whereas individuals far from estimated diagnosis appear cognitively normal. Classification schemes that incorporate both genetic and phenotypic information may be more sensitive for tracking neurocognitive signs of disease progression.

Background: Despite the need for significant clinical intervention owing to the psychiatric manifestations of Huntington disease (HD), there has been a paucity of studies specifically designed to evaluate these symptoms prior to disease diagnosis.Objectives: To investigate whether the Symptom Checklist 90-Revised (SCL-90-R) and the Center for Epidemiological Studies Depression Scale can be used to detect psychiatric manifestations among preclinical mutation carriers with absent or minimal motor signs of HD.Design, Setting, and Participants: Individuals at risk for or recently diagnosed with HD were recruited and then evaluated at Indiana University School of Medicine, Indianapolis. All of the subjects completed a uniform clinical evaluation that included the Unified Huntington's Disease Rating Scale-99, molecular testing to determine HD mutation status, the SCL-90-R, and the Center for Epidemiological Studies Depression Scale. The sample was divided into 4 study groups: 171 individuals in the nonmutation carrier group; 29 with minimal, if any, motor signs of HD in the preclinical mutation carrier group 1; 20 with motor abnormalities suggestive of HD in the preclinical mutation carrier group 2; and 34 in the manifest HD group.Main Outcome Measures: Scores on the SCL-90-R and Center for Epidemiological Studies Depression Scale were compared.Results: Five SCL-90-R symptom dimensions (obsessive-compulsive, interpersonal sensitivity, anxiety, paranoid ideation, and psychoticism) demonstrated a significant group effect (P <=.04). The preclinical mutation carrier group 2 and the manifest HD group scored significantly higher on all 5 dimensions as compared with the non-mutation carrier group. The preclinical mutation carrier group 2 scored significantly higher than the non-mutation carrier group for 3 of the SCL-90-R symptom dimensions (anxiety, paranoid ideation, and psychoticism). A significant group effect was found on the Center for Epidemiological Studies Depression Scale (P=.04). The frequency of depressive symptoms was significantly higher in the manifest HD group and the preclinical mutation carrier group 2 as compared with the non-mutation carrier group.Conclusion: This study identified specific psychiatric symptom dimensions that differentiate non-mutation carriers from individuals in the early preclinical stages of HD who are either symptom free or have minor nonspecific motor abnormalities.

Three cases of infection due to Mycobacterium lentiflavum, a recently described species characterized by multiple resistance to anti-mycobacterial drugs, are reported here. While one case simply adds to the number of cervical lynphadenitis reported in literature, the others concern the first isolations from pleural effusions, in a young boy with leukaemia and in an elderly patient with lung disease, respectively.

BACKGROUND:Intravascular lymphomatosis (IVL) is an uncommon systemic disease characterized by occlusion of small vessels by malignant lymphomatous cells. Central nervous system involvement usually presents as subacute encephalopathy, dementia, seizures, or multifocal cerebrovascular events.OBJECTIVE:To increase awareness about IVL, an uncommon cause of neurological disease.DESIGN:This is a retrospective case series of 8 pathologically proved cases of IVL with neurological disease. Patients were part of a pathological series collected between April 1962 and October 1998 at Indiana University School of Medicine and the Armed Forces Institute of Pathology, Washington, DC.SETTING:Neurological and neuropathological examinations were performed at tertiary referral hospitals.PATIENTS:Eleven patients were diagnosed pathologically as having IVL, but 3 were not included in this evaluation because of a lack of appropriate clinical information. Of the final sample (n = 8), there were 4 men and 4 women (mean +/- SD age, 62.9 +/- 9.9 years).RESULTS:All 8 patients had focal neurological deficits, 7 had encephalopathy or dementia, 5 had epileptic seizures, and 2 had myelopathy. Death occurred at a mean of 7.7 months (range, 1-24 months) after the onset of symptoms. All patients had elevated cerebrospinal fluid protein levels, 4 had pleocytosis, and 2 had an elevated IgG level in their cerebrospinal fluid. Of the 4 patients who underwent a brain biopsy, 1 was diagnosed as having IVL before death.CONCLUSIONS:Intravascular lymphomatosis is an uncommon disease with a myriad of potential neurological manifestations. Diagnosis requires a high index of suspicion and a pathological examination. If diagnosed early, aggressive chemotherapy is potentially curative, although the overall prognosis remains dismal.

Conocer las características clínicas, microbiológicas, diagnósticas y terapéuticas de los pacientes con Fasciola hepatica en nuestro hospital. Se revisan los enfermos con F. hepatica diagnosticados entre 1975 y 1999 en el Hospital de Aránzazu de San Sebastián. El diagnóstico se hizo por visualizaciónde los parásitos adultos y/o presencia de los huevos en las heces y/o positividad de las pruebas serológicas junto con síntomas de parasitosis. Se incluyó a 37 casos (23 varones y 14 mujeres) de edades comprendidas entre 19 y 71 años. La ingestión de berros se comprobó en 27. En 7 casos se trataba de un brote familiar. Treinta y dos se encontraban en la fase de invasión hepática y cinco en la de parasitación de la vía biliar. Los rasgos más habituales fueron: eosinofilia (91,8%), síndrome constitucional (75,6%), elevación de la fosfatasa alcalina (74,2%) y dolor abdominal (72,9%). Se observaron fasciolas adultas en la vía biliar en tres y huevos en las heces en seis. La hemaglutinacion indirecta fue ≥ 1/1.280 en 13 de 27 casos. La laparoscopia en 12 de 13 y las pruebas de imagen en 13 de 31 aportaron datos relevantes para confirmar la afeccion hepática. En cuatro hubo litiasis vesicular y dos de ellos, además, tenían parásitos en el colédoco. Se intervino quirúgicamente a 3 pacientes. El tratamiento con dehidroemetina y/o bithionol consiguió la curación en 30 casos, seis de los cuales precisaron varios ciclos. Los otros cuatro curaron con praziquantel. La mayoría de los pacientes de esta serie referían el consumo de berros y presentaron síntomas típicos de parasitosis. Las técnicas de imagen fueron de gran ayuda para confirmar el diagnóstico de la afección hepatobiliar. El tratamiento con dehidroemetina y/o bithionol en uno o varios ciclos consiguió la curación de la mayoría de los pacientes. To analyze the clinical, bacteriologic, diagnostic and therapeutic features of patients with Fasciola hepatica (FH) in our hospital. We reviewed all the patients with a diagnosis of fascioliasis from 1975 to 1999 in the Aranzazu Hospital in San Sebastián (Guipúzcoa, Spain). Diagnosis was made by direct vision of adult parasites during surgery and/or the presence of ova in stool examinations and/or positive serologic tests in patients with symptoms consistent with parasitosis. Thirty-seven patients were included (23 men and 14 women), aged 19 to 71 years. Ingestion of watercress was confirmed in 27. Seven cases occurred as part of familiar outbreaks. Thirty-two were in the liver invasive stage and in 5 the biliary tree was invaded. The most common features were eosinophilia (91.8%), malaise and weight loss (75.6%), elevated alkaline phosphatase (74.2%), and abdominal pain (72.9%). Adult worms in the biliary ducts were observed in 3 patients and ova in feces were observed in 6. In 13 of 27 patients indirect hemagglutination test was (1/1,280. Data significant to confirmation of liver involvement were provided by laparoscopy in 12 of 13 patients and by imaging techniques in 13 of 31 patients. Four patients had cholelithiasis and of these, 2 also showed adult parasites in the common bile duct. Three patients underwent surgery. Therapy with dehydroemetine and/or bithionol was followed by complete remission in 30 patients, although 6 required repeat treatment cycles. The remaining 4 patients were cured by praziquantel. Most of the patients in these series reported consumption of watercress and all patients showed the symptoms typical of parasite disease. Imaging techniques proved to be of great utility in confirming the diagnosis of hepato-biliary disease. In most of the patients therapy with dehydroemetine and/or bithionol (in one or several cycles) was followed by complete remission.

BACKGROUND:To analyze the clinical, bacteriologic, diagnostic and therapeutic features of patients with Fasciola hepatica (FH) in our hospital.PATIENTS AND METHOD:We reviewed all the patients with a diagnosis of fascioliasis from 1975 to 1999 in the Aranzazu Hospital in San Sebastián (Guipúzcoa, Spain). Diagnosis was made by direct vision of adult parasites during surgery and/or the presence of ova in stool examinations and/or positive serologic tests in patients with symptoms consistent with parasitosis.RESULTS:Thirty-seven patients were included (23 men and 14 women), aged 19 to 71 years. Ingestion of watercress was confirmed in 27. Seven cases occurred as part of familiar outbreaks. Thirty-two were in the liver invasive stage and in 5 the biliary tree was invaded. The most common features were eosinophilia (91.8%), malaise and weight loss (75.6%), elevated alkaline phosphatase (74.2%), and abdominal pain (72.9%). Adult worms in the biliary ducts were observed in 3 patients and ova in feces were observed in 6. In 13 of 27 patients indirect hemagglutination test was ( 1/1,280. Data significant to confirmation of liver involvement were provided by laparoscopy in 12 of 13 patients and by imaging techniques in 13 of 31 patients. Four patients had cholelithiasis and of these, 2 also showed adult parasites in the common bile duct. Three patients underwent surgery. Therapy with dehydroemetine and/or bithionol was followed by complete remission in 30 patients, although 6 required repeat treatment cycles. The remaining 4 patients were cured by praziquantel.CONCLUSIONS:Most of the patients in these series reported consumption of watercress and all patients showed the symptoms typical of parasite disease. Imaging techniques proved to be of great utility in confirming the diagnosis of hepato-biliary disease. In most of the patients therapy with dehydroemetine and/or bithionol (in one or several cycles) was followed by complete remission.

The aim of this study was to evaluate the sensitivity of as well as the time to detection of mycobacteria by three procedures: solid media with traditional reading, microscopy on solid media, and liquid culture using the automated nonradiometric Bactec MGIT 960 system. A total of 2832 respiratory specimens were tested, 315 of which were positive for mycobacteria. The most frequently isolated species was Mycobacterium tuberculosis (201 isolates). One hundred twenty mycobacteria other than tuberculosis were isolated, 72 of which were Mycobacterium xenopi strains. Sensitivity of each of the different media compared to all media combined for growth of Mycobacterium tuberculosis was 93%, 76.1%, 79.6%, and 75.1% for Bactec MGIT 960, Middlebrook 7H11 plates, Löwenstein-Jensen, and Coletsos, respectively. Sensitivity of the Bactec MGIT 960 for detection of all mycobacterial isolates was 75.1%. When this automated system was supplemented with visual inspection, the sensitivity increased to 89.4%. The sensitivity of Middlebrook 7H11 plates, Löwenstein-Jensen, and Coletsos was 50.8%, 60.7%, and 52.3%, respectively. Time to detection of Mycobacterium tuberculosis using the Bactec MGIT 960 system and Middlebrook 7H11 plates with microscopic reading was 12.7 and 13 days, respectively; using the traditional Löwenstein-Jensen and Coletsos media, time to detection was 22.8 and 22.7 days, respectively.

Background: Embolic occlusion of intracranial vessels can be caused by material arising proximally, most commonly from the heart, the aorta, or the carotid or vertebral arteries, and rarely from systemic veins. May-Thurner syndrome is an uncommon condition in which there is impaired venous return because of compression of the left common iliac vein by the overlying right common iliac artery, resulting in iliofemoral deep venous thrombosis.Objective: To describe a young patient with presumed paradoxical embolism to the basilar apex associated with a patent foramen ovale and May-Thurner syndrome.Design: Single case report.Results: A 16-year-old girl with a history of bulimia and oral contraceptive use had a "top of the basilar" syndrome. She was found to have a patent foramen ovale on transthoracic and transesophageal echocardiography. Magnetic resonance venography of the lower extremities revealed May-Thurner syndrome. Antiphospholipid antibodies (antiphosphatidylserine, anticardiolipin, and antiphosphatidyl-ethanolamine), factor V Leiden mutation by polymerase chain reaction, and homocyst(e)ine levels were normal. Anticoagulation with intravenous unfractionated heparin sodium followed by warfarin sodium was used, resulting in resolution of her neurologic deficits.Conclusions: Deep venous thrombosis is notorious for its variable clinical manifestations and the potential dire consequences of a missed diagnosis. Physicians caring for patients with presumed paradoxical embolism should assess for May-Thurner syndrome.