A 52-year-old woman with dyskinesia, epilepsy and gait disturbance]

We report a 52-year-old Japanese woman who developed dyskinesia, epilepsy, and gait disturbance. She was well until 35 years of age, when she noted the onset of gait disturbance. She also noted abnormal involuntary movements in her limbs. She also noted dysarthria at age 38. A neurologist examined her at age 41. The neurologist found cerebellar ataxia and dyskinesia. The atrophy of the brain stem and the cerebellum was on CT. She started to have generalized convulsion with loss of consciousness. Dementia became apparent at age 40. In October, 1993, she became psychotic in which she behaved violently taking off her clothes shouting as "Fire". She was treated with major tranquilizers and became quiet. However, choreic movements became prominent. Her subsequent course was complicated with dysphagia, dementia, convulsion, and frequent bouts of pneumonia. She expired on January 24, 2000 after developing pneumonia. Her father and one sibling had similar motor disturbances. She was discussed in a neurological CPC. The chief discussant arrived at conclusion that the patient had dentatorubral-pallidoluysian atrophy. Most of the participants agreed with this diagnosis. Postmortem examination revealed that entire brain looked smaller than normal including the brain stem and the cerebellum. The cerebellar dentate nucleus showed loss of neurons and gliosis; glumose degenerations were also seen. The external segment of the pallidum showed neuronal loss and gliosis. The subthalamic nucleus showed gliosis without neuronal loss. A demyelinated focus was found in the pons; the lesion looked similar to central pontine myelinolysis. The cerebral white matters were unremarkable. Other areas were unremarkable. The pathological diagnosis was dentatorubral-pallidoluysian atrophy. The pathologic lesion which might explain her dementia was not apparent.     

Increased expression of mRNAs for microtubule disassembly molecules during nerve regeneration

The mRNA expression of the microtubule disassembly molecules (SCG10, stathmin, SCLIP and RB3) in response to nerve injury was examined using a rat hypoglossal nerve injury model. After nerve injury prominent increase in mRNA expression of SCG10, stathmin and RB3 was observed, while only slight increase in SCLIP mRNA was observed in injured motor neurons. The increase in SCG10 and RB3 mRNA expression was quicker than that of stathmin and SCLIP. All the elevated signals decreased gradually to control levels by 4 weeks after nerve injury.     

Developmental changes in expression of small GTPase RhoG mRNA in the rat brain

We have recently reported that RhoG, a member of Rho family small GTPases, is involved in neurite outgrowth in cultured neuronal cells. Here, we report the expression of RhoG mRNA in the developing rat brain by in situ hybridization analysis. At embryonic day 16, RhoG expression was observed throughout the ventricular zone, but was down-regulated in the region at birth. On the other hand, RhoG expression at postnatal day 20 was highly enriched in white matter tracts, including the corpus callosum, the anterior commissure, and the cerebellar white matter, and double-labeling experiments demonstrated that major RhoG-expressing cells in white matter tracts were oligodendrocytes. These results suggest distinct pre- and postnatal roles of RhoG in the development of the central nervous system.     

Effects of anticholinergic drug withdrawal on memory, regional cerebral blood flow and extrapyramidal side effects in schizophrenic patients

It has been suggested that anticholinergic drugs impair immediate memory and working memory in patients with schizophrenia. Opinions remain divided as to the influence of anticholinergic drug withdrawal on the psychopathology and extrapyramidal side effects (EPS) in these patients. In our previous study, regional cerebral blood flow (rCBF) was reduced in all regions of patients taking anticholinergic drugs. Anticholinergic drugs were withdrawn in 21 schizophrenic inpatients. Immediate and verbal working memory, rCBF, psychopathology, and EPS were investigated before and after anticholinergic withdrawal. There was improvement in immediate memory, verbal working memory, and psychopathology, as well as an increase in rCBF after withdrawal from anticholinergic drugs. EPS showed no significant changes. Factors that may predict the improvement of immediate memory after withdrawal of anticholinergic drugs are more severe baseline psychopathology and use of a higher anticholinergic drug dose at baseline. Improvement of working memory may be predicted by a higher baseline rCBF in the left anterior cerebral artery region. Withdrawal from anticholinergics should be considered in schizophrenic patients, and it is important to taper these drugs over at least four weeks.     

Development of a tree model that allows simple estimation of the required care level using the items of the basic investigation of long-term care insurance

In long-term care insurance, the required care level of the disabled elderly is calculated from the results of the basic investigation. However, this calculation involves complex mathematical processes, and the estimation of the required care level at small facilities is difficult. We, therefore, developed a tree model that allows simple estimation of the required care level from the state of noticeable disabilities in daily activities. The model was prepared separately for dementia and physical disabilities. From the patients being cared for at Higashiyama Geriatric Hospital for the Elderly who had undergone primary rating, a total of 240 individuals consisting of 20 each in each of the 6 required care levels for both dementia and physical disabilities were selected, and the results of their primary rating were reviewed. "Putting on and taking off a jacket" and "care after urination", in which the required care levels increase relatively consistently as the investigation items progressed from those for "independent" to those for "totally assisted", were selected as the first selection items in dementia and physical disability models respectively. In a dementia model, the state of "putting on and taking off a jacket" and "care after urination" were matched for various required care levels as follows: "Independent"-->assistance needed, "observation needed" and "independent" in "standing up"-->required care level 1, "observation needed" and "not independent" in "standing up"-->required care level 2, "partly assisted"-->required care level 3, "totally assisted" and "not totally assisted" in "eating"-->required care level 4, and "totally assisted" and "totally assisted" in "eating"-->required care level 5. In a physical disability model, the state of "care after urination" was matched for various required care levels as follows: "Independent" and "independent" in "walking"-->assistance needed, "independent" and "not independent" in "walking"-->required care level 1, "direct or indirect assistance"-->required care level 2, "totally assisted" and "independent" or "observation needed" in "eating"-->required care level 3, "totally assisted" and "partly assisted" in "eating"-->required care level 4, "totally assisted" and "totally assisted" in "eating"-->required care level 5. The accuracy rate, i.e. the frequency of complete matching between the estimation of the required care level using this tree and that of the primary rating, was 71.1% in those with dementia and 66.7% in those with physical disabilities. The near accuracy rate, i.e. the frequency of matching between the two estimations within one rank higher or lower was 98.3% in those with dementia and 99.2% in those with physical disabilities. From these results, this tree model is considered to be useful for clinical rating.     

Early diagnosis and radical surgical treatment of Budd-Chiari syndrome

We report a 26-year-old woman who was diagnosed with Budd-Chiari syndrome following consultation for a skin nodule in the lower extremity. Histopathological examination of a biopsy specimen showed features of erythema induratum. As part of the diagnostic work-up, chest roentgenography performed to rule out possible tuberculosis showed enlarged right lower mediastinum. Computed tomography identified a dilated azygos vein and obstruction of the inferior vena cava near the liver. Liver function tests and blood cell counts were all within normal limit and no sign of portal hypertension was noted except for mild splenomegaly. Although angioplasty by balloon catheter resulted in recanalization of the obstructed inferior vena cava, obstruction of the inferior vena cava appeared again 2 months later. One-stage surgical reconstruction of the vascular abnormalities affecting inferior vena cava and hepatic vein using autologous pericardial patch was performed 11 months after angioplasty, which resulted in normalization of blood flow. Examination of a liver biopsy obtained intraoperatively revealed hepatic fibrosis compatible with early-stage Budd-Chiari syndrome. No complications were noted postoperatively and the nodular lesion in the lower extremity disappeared after surgery.     

Proton MR spectroscopic and diffusion tensor brain MR imaging in X-linked adrenoleukodystrophy: initial experience

PURPOSE: To compare conventional magnetic resonance (MR) imaging, proton MR spectroscopic imaging, and diffusion tensor (DT) MR imaging findings in patients with X chromosome-linked adrenoleukodystrophy (X-ALD). MATERIALS AND METHODS: Multisection proton MR spectroscopy and DT imaging were performed in 11 patients with X-ALD and in 11 healthy control subjects. Quantitative measures of N-acetylaspartate (NAA), choline, and creatine values and of isotropic apparent diffusion coefficient (IADC) and fractional anisotropy (FA) were obtained from coregistered regions of interest. DT imaging and metabolic parameters were compared by using regression analysis. In addition, differences in DT imaging and metabolite measurements between normal- and abnormal-appearing white matter on conventional MR images were evaluated by using a nonparametric (Mann-Whitney) test. RESULTS: A strong logarithmic relationship between NAA value and FA (r = 0.64, P <.001) and an inverse logarithmic relationship were found between NAA value and IADC (r = -0.69, P <.001). Creatine and choline values correlated poorly with IADC and FA. In the normal-appearing white matter of asymptomatic patients, the NAA value was 17% lower than that in the healthy control subjects (P =.016), whereas no significant difference in DT imaging measures was seen in these regions. CONCLUSION: In patients with X-ALD, MR spectroscopic imaging can depict abnormalities in white matter that have a normal appearance on both conventional MR and DT images; this finding suggests that it may be the most sensitive technique for detecting early abnormalities of demyelination or axonal loss in patients with X-ALD.     

Variation in FDG uptakes in different regions in normal human brain as a function of the time (30 and 60 minutes) after injection of FDG

OBJECTIVE: The authors' goal was to determine whether FDG uptakes in various regions of the brain are different for early and late scanning time in positron emission tomography (PET). METHOD: F-18 fluorodeoxyglucose (FDG) PET was performed on 15 healthy normal subjects to obtain early and late acquisition glucose metabolic images (30 and 60 min after FDG injection), respectively. The two sets of images were compared in a voxel-by-voxel analysis. RESULTS: In the bilateral posterior cingulate gyrus, parietal and frontal association cortices, and subcallosal cortices, the FDG uptakes were larger on the late scan image than on the early scan image, and the FDG uptakes were larger in the cerebellar hemisphere, vermis and frontal basis on the early scan image than on the late scan image. CONCLUSIONS: These results suggest that there are different regional FDG uptakes depending on the scanning time after FDG injection and we must be careful in replacing conventional FDG PET scanning with early scanning in FDG PET study.     

Immunohistochemical detection of chemokines in human skin wounds and its application to wound age determination

Immunohistochemical studies on the time-dependent expression of the chemokines such as interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-1α were performed on 50 human skin wounds with different wound ages (group I 0–12 h, group II 1–4 days, group III 7–14 days and group IV 17–21 days). In the wound specimens with wound ages between 4 and 12 h, neutrophils mainly showed positive reactions for IL-8, MCP-1 and MIP-1α. With increasing wound ages, macrophages and fibroblasts were positively stained with anti-IL-8, MIP-1α and MCP-1 antibodies. Morphometrically, there was a similar distribution in the positive ratios of the inflammatory cells among IL-8, MCP-1 and MIP-1α. The positive ratios of each chemokine were very low in group I and a considerable increase of the positive ratios in each chemokine was observed in group II (mean ± standard error IL-8: 59.8 ± 2.1%, MCP-1: 42.4 ± 3.1% and MIP-1α: 50.4 ± 3.7%). Although the positive ratios for each chemokine gradually decreased according to the wound age, the mean positive ratios in groups III and IV were significantly higher than those in group I. From the forensic aspect, these chemokines are considered useful markers for wound age determination. Thus, ratios of > 50% for IL-8, > 30% for MCP-1 or > 40% for MIP-1α indicate a wound age of at least 1 day. Moreover, the combined investigation of these three chemokines can make wound age determination more objective and accurate. Received: 30 May 2001 / Accepted: 14 August 2001     

Cytogenetic and cellular events during radiation-induced thymic lymphomagenesis in the p53 heterozygous (+/-) B10 mouse

PURPOSE: Cellular and cytogenetic events in radiation-induced thymic lymphomagenesis were investigated in the p53 heterozygous (+/-) mouse following a single dose of whole-body irradiation. MATERIALS AND METHODS: The loss of the wild-type p53 allele and microsatellite markers of chromosome 11 in thymic lymphomas that developed in the p53 heterozygous (+/-) mouse after irradiation, and the stage at which prelymphoma cells appeared were analysed. RESULTS: The p53 heterozygous mouse developed thymic lymphomas in a dose-dependent manner. The loss of the wild-type p53 allele (loss of heterozygosity; LOH) occurred in almost all thymic lymphomas induced in the irradiated p53 heterozygous mouse. Cytogenetic analysis for the mechanism of LOH strongly suggested that the loss of the wild-type p53 gene in the lymphomas was caused by duplication of the disrupted allele through either homologous recombination or non-disjunctional chromosome duplication. The assay for prelymphoma cells suggested that a critical event in the development of prelymphoma cells occurred at least 3 weeks after irradiation. CONCLUSIONS: The loss of the wild-type p53 gene in thymocytes of the p53 heterozygous mouse may precede the development of prelymphoma cells after irradiation and be a valuable marker of radiation-induced leukemogenesis.