Yusuke Hazama

Brain perfusion differences in Parkinsonian disorders

We aimed to objectively examine the brain perfusion differences between PD, Parkinson variant of multiple system atrophy, and progressive supranuclear palsy. 99mTc ethylcysteinate dimer single‐photon emission CT (SPECT) was performed in 28 patients with PD, 12 with Parkinson variant of multiple system atrophy, 19 with progressive supranuclear palsy, and 17 age‐ and sex‐matched control subjects. A voxel‐by‐voxel group analysis, using statistical parametric mapping 8, was performed to detect the differences of regional cerebral blood flow among three diseases and control groups. Regional cerebral blood flow was measured using the noninvasive Patlak plot method and calculated using a fully automated region of interest technique. Progressive supranuclear palsy showed decreased regional cerebral blood flow in the cingulate gyrus and thalamus, whereas Parkinson variant of multiple system atrophy showed decreased regional cerebral blood flow in the cerebellum, compared with other patients and controls. Regional cerebral blood flow in the thalamus could be used to discriminate progressive supranuclear palsy from other diseases and control subjects with high sensitivity. These findings suggest that parkinsonian disorders, such as PD, Parkinson variant of multiple system atrophy, and progressive supranuclear palsy show a distinct SPECT pattern in the frontal cortex, thalamus, and cerebellum. Moreover, the measurements of regional cerebral blood flow in the thalamus and cerebellum may be helpful in screening for the differential diagnosis of parkinsonian syndrome.

Corticobasal degeneration presenting with progressive conduction aphasia

We report the case of a woman with primary progressive aphasia (PPA) presenting with conduction aphasia. Neurological findings showed bilateral finger tremor and signe de poignet figé in her right hand. Memory, orientation, and activities of daily living were well preserved. Linguistic examination showed severe impairment in repetition, fluent spontaneous speech with phonemic paraphasia, and relatively well preserved comprehension. Limb-kinetic apraxia and parkinsonism were not observed during the course of her illness. T1-weighted magnetic resonance imaging revealed severe atrophy of the left temporal lobe and dilatation of the left Sylvian fissure. Neuropathological findings demonstrated the most severe atrophy in the left superior temporal gyrus and Gallyas-Braak-positive or phosphorylated tau-immunoreactive cytoskeletal structures, which were consistent with corticobasal degeneration (CBD). We speculate that the progressive conduction aphasia of our patient might have been caused by left temporal lobe impairment. We suggest that progressive conduction aphasia may be a feature of CBD presenting with PPA.

Evaluation of the effect of thyrotropin releasing hormone (TRH) on regional cerebral blood flow in spinocerebellar degeneration using 3DSRT

Thyrotropin releasing hormone (TRH) therapy improves cerebellar ataxia in patients with spinocerebellar degeneration (SCD). We investigated the effect of TRH on regional cerebral blood flow (rCBF) using the fully automated region of interest (ROI) technique, 3DSRT. Ten patients with SCD received TRH intravenously (2 mg/day) for 14 days and underwent brain perfusion single photon emission computed tomography before and after therapy. Clinical efficacy was assessed using the International Cooperative Ataxia Rating Scale (ICARS). The rCBF in each ROI was measured using the noninvasive Patlak plot method and calculated using 3DSRT. TRH significantly improved the ICARS scores and increased rCBF in the callosomarginal segment and cerebellum. Cerebellar rCBF increased in 4 of 5 patients with improved ICARS scores and in 3 of 5 patients without improved ICARS scores after TRH therapy. The correlation between the change in cerebellar rCBF and the improved ICARS score, however, was not significant. These findings indicate that TRH therapy may increase cerebellar rCBF in some patients with cerebellar forms of SCD and that 3DSRT may be useful for evaluating the efficacy of TRH for increasing CBF. The beneficial effects of TRH may be due to increased cerebellar rCBF or the increased rCBF may be a secondary effect of TRH therapy.

Evaluation of the effects of thyrotropin releasing hormone (TRH) therapy on regional cerebral blood flow in the cerebellar variant of multiple system atrophy using 3DSRT.

Thyrotropin releasing hormone (TRH) improves cerebellar ataxia and cerebellar perfusion in patients with spinocerebellar degeneration. It is not known whether TRH therapy can improve the cerebellar regional cerebral blood flow (rCBF) or not in patients with cerebellar variant of multiple‐system atrophy (MSA‐C).

ROLE OF UBIQUITIN-PROTEASOME PROTEOLYSIS IN MUSCLE FIBER DESTRUCTION IN EXPERIMENTAL CHLOROQUINE-INDUCED MYOPATHY

Previous studies have documented the presence of rimmed vacuoles, atrophic fibers, and increased lysosomal cathepsin activity in skeletal muscle from animal models of chloroquine‐induced myopathy, suggesting that muscle fibers in this type of myopathy may be degraded via the lysosomal‐proteolysis pathway. Given recent evidence of abnormal ubiquitin accumulation in rimmed vacuoles, in this study we chose to examine the significance of the ubiquitin–proteasome proteolytic system in the process of muscle fiber destruction in experimental chloroquine myopathy. Expression of ubiquitin, 26S proteasome proteins, and ubiquitin ligases, such as muscle‐specific RING finger‐1 (MuRF‐1) and atrogin‐1/muscle atrophy F‐box protein (MAFbx), was analyzed in innervated and denervated rat soleus muscles after treatment with either saline or chloroquine. Abnormal accumulation of rimmed vacuoles was observed only in chloroquine‐treated denervated muscles. Ubiquitin and proteasome immunostaining, and ubiquitin, MuRF‐1, and atrogin‐1/MAFbx mRNAs were significantly increased in denervated soleus muscles from saline‐ and chloroquine‐treated rats when compared with contralateral innervated muscles. Further, ubiquitin and ubiquitin ligase mRNA levels were higher in denervated muscles from chloroquine‐treated rats when compared with saline‐treated rats. These data demonstrate increased proteasomes and ubiquitin in denervated muscles from chloroquine‐treated rats and suggest that the ubiquitin–proteasome proteolysis pathway as well as the lysosomal‐proteolysis pathway mediate muscle fiber destruction in experimental chloroquine myopathy. Muscle Nerve 39: 521–528, 2009

Relationship between thyroid hormone levels and regional cerebral blood flow in Alzheimer disease.

Subclinical thyroid disease and even variations in thyroid function within the normal range is associated with cognitive function and a risk of Alzheimer disease (AD). Several studies reported the effect of thyroid hormones on cerebral blood flow. The aim of this study was to objectively evaluate regional cerebral blood flow (rCBF) in association with thyroid hormone levels within the normal range in patients with AD. Serum thyroid-stimulating hormone (TSH), free T3, and free T4 levels were measured in 62 patients with AD (23 men and 39 women; age 56 to 91 y; mean age 77.3 y) and 27 control subjects (9 men and 18 women; age 61 to 93 y; mean age 75.8 y). The 99mTc ethylcysteinate dimer single photon emission computed tomography was performed in all subjects. The rCBF in the region of interest was measured by the noninvasive Patlak plot method and calculated using FineSRT, which is a fully automated region of interest technique. No significant correlation was found between thyroid hormone levels and Mini-Mental State Examination scores or global CBF values. Serum levels of TSH, but not free T3 or free T4, were significantly inversely correlated with rCBF in the middle and inferior temporal regions of right cerebral hemisphere in patients with AD. Control subjects showed no significant correlation between thyroid hormone levels and rCBF. Although these findings of a regional relationship must be considers preliminary, this study proposed the hypothesis that altered TSH levels within the normal range may be related to brain perfusion in right temporal region.

Portal‐systemic shunt encephalopathy presenting with diffuse cerebral white matter lesion: An autopsy case

We report herein an autopsy case of portal‐systemic encephalopathy (PSE) presenting with diffuse tissue rarefaction in the cerebral deep white matter. Clinically, the patient showed recurrent episodes of unconsciousness, abnormal behavior and urinary incontinence, as well as flapping tremor. Cognitive impairment and peripheral neuropathy developed following recurrent episodes. Although conventional arterial portography revealed a small portal‐systemic collateral vessel of a left gastro‐renal venous shunt, abdominal CT and liver biopsy showed no evidence of liver cirrhosis and serum ammonia level showed a mild increase. T2‐weighted MRI demonstrated symmetrical signal hyperintensities in the deep white matter. Neuropathological findings showed Alzheimer type II astrocytes in the deep layers of the cerebral cortices and severe tissue rarefaction with no or slight reactive astrocytosis in the subcortical and deep white matter. These white matter changes have been reported infrequently in patients with PSE. The present case suggests that chronic PSE without liver cirrhosis may develop diffuse white matter lesions.