In vivo evidence of cerebellar atrophy and cerebral white matter loss in Huntington disease.

OBJECTIVE: To investigate the regional pattern of white matter and cerebellar changes, as well as subcortical and cortical changes, in Huntington disease (HD) using morphometric analyses of structural MRI. METHODS: Fifteen individuals with HD and 22 controls were studied; groups were similar in age and education. Primary analyses defined six subcortical regions, the gray and white matter of primary cortical lobes and cerebellum, and abnormal signal in the cerebral white matter. RESULTS: As expected, basal ganglia and cerebral cortical gray matter volumes were significantly smaller in HD. The HD group also demonstrated significant cerebral white matter loss and an increase in the amount of abnormal signal in the white matter; occipital white matter appeared more affected than other cerebral white matter regions. Cortical gray and white matter measures were significantly related to caudate volume. Cerebellar gray and white matter volumes were both smaller in HD. CONCLUSIONS: The cerebellum and the integrity of cerebral white matter may play a more significant role in the symptomatology of HD than previously thought. Furthermore, changes in cortical gray and cerebral white matter were related to caudate atrophy, supporting a similar mechanism of degeneration.

Rate and correlates of weight change in Huntington's disease.

OBJECTIVE: To determine the rate and correlates of weight change in a large, well characterised sample of patients with Huntington's disease followed at 44 sites by the Huntington Study Group. PARTICIPANTS AND METHODS: Weight change was assessed in 927 adults with a definite diagnosis of Huntington's disease who were followed prospectively for (mean (SD)) 3.4 (1.4) years. The unified Huntington's disease rating scale was used to assess weight, motor dysfunction (including chorea and dystonia), depressive symptoms, and functional decline. RESULTS: Random effects modelling determined that patients gained an average of 0.11 (1.7) kg/year and their chorea scores increased by 0.36 (0.78) points/year. There were significant but weak relations between weight loss and increasingly severe chorea (r = -0.13), worse baseline motor performance (r = -0.12), less severe baseline depressed mood (r = 0.14), and poorer baseline independence ratings (r = 0.07). Patients who were within 0 to 2 years of symptom onset at the time of the baseline visit gained more weight than those with longer disease duration. CONCLUSIONS: Weight loss following symptom onset is not a consistent feature of Huntington's disease. The mechanisms contributing to weight change in this condition are unclear and probably multifactorial. Future studies examining asymptomatic carriers of the mutation could be helpful in identifying incipience of low body weight and may be better suited for identifying clinical correlates of weight loss than studies in symptomatic patients.

Preclinical evaluation of 5-aminolevulinic acid-based photodynamic therapy for canine transitional cell carcinoma.

As a prelude to photodynamic therapy, 5-aminolevulinic acid (ALA) was given orally to healthy dogs. ALA-induced protoporphyrin IX (PpIX) fluorescence significantly increased in the mucosa of the urinary bladder in an ALA dose-dependent fashion. Vomiting occurred after ALA administration in 70% of the dogs but did not affect PpIX fluorescence. ALA-based photodynamic therapy (PDT) of the urinary bladder in healthy dogs caused only submucosal oedema within the bladder wall. No haematologic or serum biochemistry abnormalities were observed after ALA administration. Microscopic haematuria was observed in all the dogs after PDT but was mild and self limiting. ALA-based PDT was administered to six dogs with transitional cell carcinoma (TCC) of the lower urinary tract. ALA-based PDT resulted in tumour progression-free intervals from 4 to 34 weeks in five dogs; one dog with pre-existing hydronephrosis died shortly after PDT. Dogs with TCC represent an outbred, spontaneous, tumour model for developing PDT protocols for humans with bladder cancer.

Cognitive profiles differ in autopsy-confirmed frontotemporal dementia and AD.

BACKGROUND: Frontotemporal dementia (FTD) is currently distinguished from AD primarily on the basis of behavioral features because studies of cognition have shown negligible or inconsistent differences. However, the poor discriminability of cognitive measures may relate to reliance on imprecise clinically diagnosed groups. Therefore, a retrospective examination of neuropsychological test performance in autopsy-confirmed patients is warranted. OBJECTIVE: To compare the pattern of cognitive deficits exhibited by patients with autopsy-confirmed FTD and AD. METHODS: The profiles of cognitive deficits exhibited by patients with neuropathologic diagnosis of FTD (n = 14) or AD (n = 28) were compared. The Mattis Dementia Rating Scale (MDRS), letter and category fluency tests, Wechsler Intelligence Scale for Children-Revised block design test, Boston naming test, and clock drawing test were administered. RESULTS: Multivariate analysis of covariance controlling for age, education, and level of dementia revealed that patients with FTD performed significantly worse than patients with AD on letter and category fluency tests but significantly better on the MDRS memory subscale, block design test, and clock drawing test. A logistic regression model, validated in an independent clinical sample, used letter fluency, MDRS memory, and block design scores to correctly classify 91% of AD patients and 77% of FTD patients. CONCLUSIONS: A double dissociation in the pattern of cognitive deficits exhibited by FTD and AD patients was demonstrated. The FTD patients were more impaired than AD patients on word generation tasks (i.e., verbal fluency) that are sensitive to frontal lobe dysfunction but less impaired on tests of memory and visuospatial abilities sensitive to dysfunction of medial temporal and parietal association cortices.

Use of laser photocoagulation for treatment of cutaneous angiomatosis in one dog and two cats.

One dog and 2 cats were evaluated because of multiple progressively enlarging cutaneous vascular plaques. Biopsies were performed and revealed small well-circumscribed dermal nodules of dilated fully enclosed blood-filled spaces lined by single layers of endothelial cells aligned on thin fibrous walls, with minimal mitotic activity. A diagnosis of cutaneous angiomatosis was made in all 3 animals. Cutaneous angiomatosis is a progressive proliferative lesion of vascular tissue involving the dermis and subcutaneous tissues of dogs and cats. Lasers of selected wavelengths have been used to induce photothermal coagulation of hemoglobin-containing cutaneous lesions in humans; argon-pumped dye and neodymium:yttrium-aluminum-garnet lasers were used to treat the cutaneous lesions in the animals of this report. Laser treatment may provide an alternative to wide surgical resection or limb amputation for management of this condition in veterinary patients.

Cortical bone healing following laser osteotomy using 6.1 microm wavelength.

BACKGROUND AND OBJECTIVE: Use of laser wavelengths in the 6.1 microm (amide I) to 6.45 microm (amide II) regions and a macropulse width of 4.0 microseconds delivered by a computer-controlled delivery system have produced clean, deep cortical bone ablations with minimal collateral thermal injury and no char formation. The purpose of this study was to evaluate the healing of cortical bone following 6.1 microm wavelength laser osteotomy using a 4.0 microsecond pulse, and compare that response to the response of similar osteotomies made with a standard pneumatic surgical bone saw. STUDY DESIGN/MATERIALS AND METHODS: Sixteen mature rabbits were divided equally into 2, 4, 6 and 8-week post-surgical survival groups. A nitrogen driven sagittal bone saw and an FEL generating 6.1 microm wavelength in 4.0 microsecond macropulses of 22.5 +/- 2.5 mJ/pulse directed into a 200 microm diameter spot were used to make 6.6 mm linear cuts into rabbit tibial cortex, and the healing response over time was monitored. Bone saw cuts were made halfway through the thickness of the cortex. Laser cuts were directed by a computer-controlled delivery system, and were either partial or full thickness cortical cuts. Location of the cortical bone cuts (saw or laser, partial or full thickness cut, proximal or distal, medial right or medial left tibia) were randomly assigned. At each predetermined post-surgical time point, rabbits of the appropriate group were euthanized, and the tibias of each subject collected, processed for histologic evaluation, and analyzed by light microscopy. RESULTS: At 2 weeks post-surgery, bone saw cuts showed no evidence of a healing response, while both the partial and full laser cut sites were filled with trabecular bone and primitive bone marrow. By 4 weeks post-surgery, the bone saw cuts showed filling of the defect with trabecular bone and primitive marrow, and an intense osteonal remodeling of the original cortex adjacent to the cuts was evident. All laser cut defects were filled, reactive periosteal bone was being converted to osteons and consolidating, and secondary osteons were appearing in the original cortex. At 6 weeks following surgery, the bone saw defects were filed with a mixture of woven and lamellar bone. All laser defects were filled with lamellar osteons and woven bone, the osteons were remodeling from primary to secondary osteons. By 8 weeks following the surgery, all bone saw and laser cut specimens revealed complete healing. CONCLUSIONS: Histologic evaluation of osteotomy sites made in skeletally mature rabbit tibia using the 6.1 microm wavelength, 4.0 microsecond macropulse FEL, delivered at 6 Hz at the osteotomy site, reveals a healing response which is at least as good as the healing of bone saw osteotomies, and appears to proceed at a faster rate during the first 2-4 weeks following surgery.

Detection of mild cognitive deficits in Parkinson's disease patients with the WAIS-R NI.

The relative insensitivity of traditional IQ tests to mild cognitive deficits has led investigators to develop a version of the widely used Wechsler intelligence scales that allows quantitative analysis of underlying qualitative responses. This instrument, the Wechsler Adult Intelligence Scale-Revised as a Neuropsychological Instrument (WAIS-R NI) was administered to 16 Parkinson's disease (PD) patients and 30 normal controls (NC). The 2 groups did not differ significantly in mean age or education, or on their mean Mattis Dementia Rating Scale score. Relative to NC participants, PD patients showed decreased visual attention span, longer response latencies, slower visuomotor processing, and more stimulus-bound errors. Many of the WAIS-R NI measures were able to detect cognitive impairment in a greater percentage of patients than the traditional WAIS-R measures, making it easier to identify deficits that could affect quality of life early in the course of the disease.

Three words three shapes: A clinical test of memory.

Three Words - Three Shapes was designed as an easy "bedside" test for elderly patients that assesses verbal and nonverbal memory within the same modality. In the present study, it was administered to patients with probable Alzheimer's disease (PRAD), a control group of non-demented older subjects (NC) and a group of patients with Korsakoff's amnesia (KA). Incidental recall and several other measures of learning, retention and recognition differentiated control from PRAD and KA subjects. PRAD and KA subjects' performance was similar, but there were some material-specific interactions. This test is relatively easy and some of the derived measures could prove useful in staging amnesia progression beyond the earliest stages of PRAD when more difficult tests yield floor effects.

Comparison of cortical bone ablations by using infrared laser wavelengths 2.9 to 9.2 microm.

BACKGROUND AND OBJECTIVE: The purpose of this study was to compare the ablation of cortical bone at wavelengths across the near and midinfrared region. STUDY DESIGN/MATERIALS AND METHODS: An free electron laser generating 4-micros macropulses at specific wavelengths between 2.9 and 9.2 microm was used to ablate cortical bone. The same pulse intensity, repetition rate, radiant exposure, number of pulses, and delivery was used for each wavelength. Tissue removal, collateral thermal injury, and morphologic characteristics of the ablation sites were measured by light and scanning electron microscopy, and compared with the infrared absorption characteristics of cortical bone. RESULTS: Within the parameters used, bone ablation was found to be wavelength dependent. Incisions were deepest where protein has strong absorption, and were most shallow where mineral is a strong absorber. No char was observed on ablation surfaces where 3.0, and 5.9-6.45 microm wavelengths were used. CONCLUSIONS: The use of wavelengths in the 6.1-microm amide I to 6.45-microm amide II region, with the pulse characteristics described, were the most efficient for cutting cortical bone and produced less collateral thermal injury than cutting with a surgical bone saw. This study confirms previous observations that the ablation mechanism below plasma threshold is consistent with an explosive process driven by internal vaporization of water in a confined space and demonstrates that ablation is enhanced by using wavelengths that target the protein matrix of cortical bone.