Clinical features of frontotemporal dementia

What was once called Pick's disease has three major anatomic variants. With all three, frontotemporal brain is selectively injured whereas posterior cortical regions are spared. These three clinical patterns include a bifrontal, slightly asymmetric subtype with more involvement of the right frontotemporal region called frontotemporal dementia or the frontal variant of FTD (fvFTD), a temporal-predominant subtype called the temporal variant of FTD or semantic dementia (SD), and a left frontal-predominant subtype called progressive nonfluent aphasia (PNFA). The three anatomic groups help to classify distinctive clinical syndromes with unique features. Careful study of these subtypes of frontotemporal dementia, using combinations of new quantitative neuroimaging, behavioral and physiological measures are yielding important information about the functioning of the brain's frontal and temporal regions. As we come to better understand the biologic basis for the three FTD clinical syndromes, new classification schemas may emerge, but our current clinical criteria serve as a strong guide to the diagnosis and separation of FTD from Alzheimer disease and other dementias.     

Comparison of family histories in FTLD subtypes and related tauopathies

Pedigrees from 269 patients with frontotemporal lobar degeneration (FTLD), including frontotemporal dementia (FTD), FTD with ALS (FTD/ALS), progressive nonfluent aphasia, semantic dementia (SD), corticobasal degeneration, and progressive supranuclear palsy were analyzed to determine the degree of heritability of these disorders. FTD/ALS was the most and SD the least heritable subtype. FTLD syndromes appear to have different etiologies and recurrence risks.     

An adolescent with chest pain-sequela of Kawasaki disease

Kawasaki disease, is an acute vasculitis of unknown etiology characterized by mucocutaneous involvement occurring in infants and young children, predominantly younger than 5 years of age. We present a case of a 19-year-old female with a prior history of Kawasaki disease as an infant who was seen in the emergency department with chest pain in the midsternal region lasting for 20 minutes with radiation to the left arm. An electrocardiogram revealed anterior repolarization abnormalities with normal echocardiogram (ECHO) findings. There was a 90% eccentric and calcified single discrete stenosis of the proximal segment of the left anterior descending artery, and the patient underwent a successful percutaneous transluminal coronary angioplasty with stent insertion. Physicians working in the emergency department setting should remain cognescent of the rarer but significant cardiac causes of chest pain while evaluating children, adolescents, and young adults.     

Uncomplicated carotid endarterectomy: factors contributing to blood pressure instability precluding safe early discharge

This study was undertaken to identify preoperative and intraoperative factors that correlate with the need for postoperative vasoactive medication (VM) use. Clinical data from 100 carotid endarterectomies (CEAs) performed in 93 patients were reviewed. Baseline comorbidities, medications, perioperative physiologic data, and operative technique were evaluated for their association with the need for postoperative VM use. Statistical analysis included univariate and multivariate logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs) reported. Hemodynamic instability affected 43 patients, of whom 32 had VM started in the postanesthesia care unit (PACU). No patient who was hemodynamically stable in the PACU later required VM. The only preoperative factor associated with a need for postoperative VM was a prior stroke (OR 4.5; 95% CI 1.2-16.2; p = .02). Intraoperative factors associated with the need for postoperative VM included use of a shunt (OR 5.1; 95% CI 1.2-22.2; p = .03) and a peak intraoperative systolic blood pressure greater than 200 mm Hg (OR 5.1; 95% CI 1.2-22.2; p = .03). The number and type of preoperative blood pressure medications, preoperative hypertension, comorbidities, symptomatic presentation, and intraoperative use of VM did not correlate with postoperative VM use. There were two strokes and no deaths. Patients undergoing CEA who are hemodynamically stable in the PACU appear to be reasonable candidates for same-day discharge and warrant further prospective study.     

Laser in situ keratomileusis for hyperopia with the LADARVision 4000 with centration on the coaxially sighted corneal light reflex

PURPOSE: To analyze the visual acuity, contrast sensitivity, and target deviations in patients who had laser in situ keratomileusis (LASIK) for primary hyperopia with the ablation centered on the coaxially sighted corneal light reflex. SETTING: University-based refractive surgery practice. METHODS: Retrospective review comprised 37 consecutive patients (61 eyes) who had LASIK for hyperopia with the LADARVision 4000 excimer laser (Alcon Laboratories). Preoperative and 3-month postoperative visual acuity and contrast sensitivity, as well as the target deviation, were assessed for each eye. The change in best spectacle-corrected visual acuity (BSCVA), best spectacle-corrected contrast sensitivity (BSCCS), and target deviation from the intended correction were analyzed. RESULTS: Postoperatively, the uncorrected visual acuity (UCVA) was 20/20 or better in 44.4% of eyes. The mean deviation from target was +0.25 diopter (D) +/- 0.82 (SD), with 65.6% of eyes within +/-0.50 D of target. None eye lost 2 or more lines of BSCVA. A loss of 3 or more patches of BSCCS were seen in 6.6% of the eyes and a loss of 4 or more patches, in 1.6%. CONCLUSION: Hyperopic LASIK with LADARVision 4000 with the ablation zone centered on the coaxially sighted corneal light reflex did not adversely affect BSCVA and BSCCS.     

Reduction of pupil size and halos with minus lenses after laser in situ keratomileusis

PURPOSE: To evaluate the amount of miosis induced by over-minused lenses and to assess subjective reduction of halos following laser in situ keratomileusis (LASIK) with such lenses. METHODS: Part I: Infrared pupil diameter was assessed in 14 patients who had not had ocular surgery. The accommodative/miotic reflex was stimulated with concave trial lenses in -1.00-D increments up to -4.00 D while viewing the 20/40 acuity line. Part II. Subjective halos around a distant light were assessed in 14 patients following LASIK for myopia, with and without a -1.00-D lens over manifest refraction. RESULTS: Part I: 100%, 79%, and 64% of patients clearly saw the 20/40 line with a -1.00-D lens, -2.00-D lens, and -3.00/-4.00-D lens, respectively. Mean pupil diameter decreased by 0.2 mm with the -1.00-D lens (P = .02), 0.5 mm with the -2.00-D lens (P = .003), 0.9 mm with the -3.00-D lens (P = .008,), and 1.1 mm with the -4.00-D lens (P = .008). Part II: 11 of 14 patients (79%) noticed a decrease in the size of the halo (30% average reduction) when over-minused by -1.00 D. CONCLUSIONS: Pupil diameters and halos decreased with a -1.00-D overcorrection in patients following LASIK. Patients with pupil-dependent night halos after LASIK may benefit from mildly over-minused lenses.     

A quality-of-life study in high-risk (thickness > = or 2 mm) cutaneous melanoma patients in a randomized trial of 1-cm versus 3-cm surgical excision margins

A quality-of-life study was carried out to test the hypothesis that melanoma patients treated with a 3-cm margin of excision suffer greater impairment of their quality of life than those treated with a 1-cm margin. The secondary aim was to determine the predictors of a poor patient perception of their excision scar. A postal questionnaire study was carried out using Hospital Anxiety and Depression (HAD), Psychosocial Adjustment of Illness Scale-Self-Report (PAIS-SR), Medical Outcomes Survey-Short Form 36 (MOS-SF36), and the Cassileth Scar questionnaires. Data were collected from 426 of the 537 patients who were mailed the questionnaires (response rate 79%). Fourteen percent had clinically significant anxiety and 5% had significant depression. A poor attitude toward quality of health care was associated with youth. Patients treated with a 3-cm margin excision had significantly poorer mental and physical function 1 mo after surgery, which disappeared within 6 mo. The greater difficulties experienced by the 3-cm margin group were particularly in their domestic, sexual, and social roles. Women, younger patients, those with poor physical and mental function after surgery, and those treated by a 3-cm margin were more likely to report a poorer perception of their scar. The poorer scar perception of patients in the 3-cm group persisted throughout the study period. Use of a 3-cm margin of excision for melanoma is associated with significantly more morbidity than use of a 1-cm margin, but this effect disappears in 6 mo. Patients treated by 3-cm excision were more likely, however, to have a persistent poor view of their scar. Youth and being female were also predictors of poor perception of the scar.     

Combination therapy for refractory idiopathic thrombocytopenic purpura in adolescents

PURPOSE: To investigate combined immunosuppressive therapy with vincristine, methylprednisolone, and prolonged cyclosporine in adolescents with refractory idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS: Ten adolescent patients with ITP refractory to previous medical management, including gluco-corticosteroid, intravenous immunoglobulin or anti-Rh (D) IgG, or splenectomy, were treated with combination immunosuppressive therapy at the University of Michigan between 1997 and 2001. Therapy consisted of weekly doses of vincristine 1.5 mg/m intravenous push (IVP) (maximum dose 2 mg), weekly methylprednisolone 100 mg/m IVP, and cyclosporine (CSA) 5 mg/kg orally twice daily (goal: CSA trough of 100-200 mg/mL). Vincristine and methylprednisolone were given weekly until the platelet count was greater than 50,000/mm for a minimum of 2 doses and a maximum of 4 doses. CSA was continued until the platelet count was normal for 3 to 6 months. RESULTS: Seven patients had continuous complete responses (platelet count normal after cessation of CSA), a median of 13 months (9-37 months) since completion of therapy. One patient had a partial response (platelet count 80-120 x 10 /L off CSA for 3 months). Two patients were nonresponders (platelet count <40 x 10 /L), one of whom had all therapy discontinued after 2 weeks due to peripheral neuropathy. The median time to response was 7 days (range 7-67 days). CSA was administered for a median of 4 months (range 0.5-19 months). CONCLUSIONS: A combination immunosuppressive approach that includes prolonged cyclosporine therapy may be promising for refractory ITP and is associated with sustained disease remissions in some patients.     

Mutant elastase in pathogenesis of cyclic and severe congenital neutropenia

Severe neutropenia is characterized by maturation arrest of myeloid cells at the promyelocyte stage of hematopoiesis. We reported that accelerated apoptosis of bone marrow myeloid progenitor cells was observed in both cyclic (CN) and severe congenital neutropenia (SCN). Short and long-term cultures of bone marrow CD34+ cells revealed reduced production of multipotent progenitors in SCN. In contrast, production of these cells was slightly elevated in CN compared with CD34+ cells from healthy volunteers. Production of myeloid-committed progenitor cells was significantly reduced in both CN and SCN. FACS analysis of CD34+ cells revealed G /G cell cycle arrest in SCN but not in CN.(0) (1) All CN patients and more than 90% of SCN patients have mutation in the neutrophil elastase (NE) gene. Molecular modeling of NE tertiary structure indicates that mutations observed in SCN are primarily located around the glycosylation sites, whereas CN mutations affect predominantly the active site. Transient expression of CN- or SCN-specific mutant NE cDNA results in impaired survival of human myeloid progenitor cells compared with control cells transfected with intact NE cDNA. We hypothesize that abnormal processing and subcellular localization of mutant NE might predetermine the etiology of cyclic or severe congenital neutropenia.