[A case of multiple sclerosis with abnormal single photon emission computed tomography (SPECT)].

A case of a 38-year-old woman with multiple sclerosis (MS) is reported. At 36 years of the age, she was admitted to our hospital because of developing unstable gait and clumsiness in her hands. After intravenous and oral administration of steroid, her neurological symptoms improved gradually. At 38 years of the age, she was readmitted because of recurrence. A neurological examination revealed severe left sided limb ataxia and trunkal ataxia. No abnormal finding was demonstrated in cranial MRI at the first and second admission. Single photon emission computed tomography (SPECT) using 123I-IMP that was performed at the second admission showed an increased accumulation of 123I-IMP in the left cerebellar hemisphere on the 14th day from the neurological onset. After the therapy of steroid, her neurological signs improved and SPECT showed no abnormality on the 62nd day. Seven months after the second episode, she was readmitted because of the same neurological symptoms and T2 weighted MRI revealed multiple high intensity area in the pons and midbrain. She was diagnosed as having definite MS. These findings in SPECT may suggest the inflammatory process of the cerebellum in the case of MS as well as acute cerebellar ataxia.

The pattern of alteration in flow velocity in the recanalized artery is related to left ventricular recovery in patients with acute infarction and successful direct balloon angioplasty.

OBJECTIVES: We evaluated the relationship between alterations in coronary flow velocity during the acute phase of acute myocardial infarction (AMI) and the recovery of left ventricular wall motion in patients who underwent successful primary angioplasty. BACKGROUND: The status of the coronary microcirculation is the major determinant of the prognosis of patients who have had successful reperfusion after AMI. Animal studies have shown that dynamic changes in regional flow are associated with the extent of infarction. Evaluation of alterations in coronary flow velocity in infarcted arteries may provide information about microcirculatory damage. METHODS: Flow velocity of the distal anterior descending artery was continuously monitored with the use of a Doppler guide wire immediately after recanalization for 18 +/- 4 h in 19 patients who underwent successful primary angioplasty after anterior AMI. Subjects were divided into two groups on the basis of the time course of alterations in average peak velocity (APV). Group D consisted of patients who had progressive decreases in APV through the next day (n = 9), and Group I comprised patients with an increase in APV after a transient decline (n = 10). Ejection fraction (EF) and regional wall motion (RWM) were assessed by left ventriculography performed on admission and at discharge. RESULTS: The APV at the end of monitoring was greater in group I than in group D. In group I, EF and RWM were significantly improved at discharge. The change in EF was greater in group I than in group D (17 +/- 9% vs. 4 +/- 9%, p = 0.007), as was the change in RWM (0.96 +/- 0.23 vs. 0.13 +/- 0.36 SD/chord, p < 0.0001). CONCLUSIONS: The alteration in flow velocity in recanalized infarcted arteries is related to left ventricular recovery. A progressive decrease in velocity after angioplasty implies no reflow, which is associated with a poor recovery of left ventricular function. Reperfusion injury may account in part for this phenomenon.

[Gerstmann-Sträussler-Scheinker syndrome with a Pro102Leu mutation in the prion protein gene and atypical MRI findings, hyperthermia, tachycardia, and hyperhidrosis].

A 64-year-old Japanese woman with Gerstmann-Sträussler-Scheinker syndrome (GSS) is reported. She was admitted to our hospital for progressive amnesia, twitching of the right upper limb, and difficulty in speaking and walking for 5 months. Physical examination revealed a fever, tachycardia, and hyperhidrosis without any evidence of inflammation or infection. Neurological examinations demonstrated dementia, frontal lobe signs, and spontaneous myoclonus. She developed akinetic mutism 4 months later. The levels of neuron-specific enolase and 14-3-3 protein were elevated in the cerebrospinal fluid, and serial EEG showed periodic synchronous discharges. DNA analysis of the prion protein gene revealed a Pro102Leu mutation and therefore she was diagnosed as GSS102. Head MRI showed abnormal high signal intensity by T2 weighted image in bilateral caudate nuclei, putamen, frontal lobes, and white matter around the posterior horn of lateral ventricles at admission, and extension to global cerebral cortex and diffuse deep white matter with marked atrophy of bilateral frontal and cerebellar cortices 4 months later. In 123I-IMP SPECT study, uptake of RI decreased slightly only in left frontal region at admission, but decreased markedly in bilateral frontal region 4 months later. Analysis of autonomic function (analysis of noradrenarine in plasma and urine, coefficient of variation of R-R intervals before and after giving atenolol, Aschner's eyeball pressure test, intracutaneous atropine and adrenaline injection test) revealed sympathetic hyperactivity but normal parasympathetic activity. This is a very rare case of GSS102 with atypical MRI findings and clinical features like Creutzfeldt-Jakob disease rather than GSS102, presenting hyperthermia, tachycardia, and hyperhidrosis caused presumably by sympathetic hyperactivity as well as fatal familial insomnia. Therefore it is suggested that some factors besides the codon mutation in the prion protein gene may influence clinical symptoms in prion disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) effects on enkephalinergic neurons in various regions of mouse brain.

In order to elucidate the effects of MPTP on enkephalinergic neurons, dopamine (DA), norepinephrine (NE), proenkephalin (PE) mRNA and met-enkephalin (ME) were measured in striatum, olfactory tubercle, and prefrontal cortex of C57/B16 mice 1 day-2 weeks following treatment with 96 mg/kg MPTP HCl (24 mg/kg i.p., twice/day for 2 days). DA and its metabolites were depleted 70% in striatum and 40% in olfactory tubercle within 1 day. In cortex, DA was unchanged, whereas homovanillic acid and NE were depleted 50 and 40% respectively by 3 days. ME increased in all three brain regions at different times whereas PE mRNA showed a different pattern in each region, with an increase in olfactory tubercle, a decrease in cortex, and in striatum, a decrease at 1 day followed by an increase at 3 days. Thus enkephalinergic neurons in each region respond differently to MPTP treatment. In striatum and olfactory tubercle. DA is depleted sufficiently to release its tonic inhibition on the enkephalinergic neurons, thereby leading to increased enkephalin synthesis. In cortex, the change in NE metabolism appears to cause a decrease of ME release and thereby a depression of PE synthesis. The possible relationship between these results and the changes observed in Parkinson's disease are discussed.

Chronic treatment of newborn rats with naltrexone alters astrocyte production of nerve growth factor.

Newborn rats were treated with the opiate antagonist naltrexone daily for 1-2 wk in order to examine the effects of endogenous opioid peptides on astrocytes during CNS development. Nerve growth factor (NGF) and cyclic AMP were measured in astrocytes cultured from cerebellum, striatum, and hippocampus of 1 d, 1 wk, and 2 wk postnatal rats. Cerebellar and striatal, but not hippocampal, astrocytes prepared from naltrexone-treated animals produced higher levels of NGF than those from controls. The turnover rate of cyclic AMP, measured following treatment of the cells with forskolin in the presence of the phosphodiesterase inhibitor IBMX, was increased in naltrexone-derived cerebellar and striatal astrocytes. Opiate receptors could not be detected on the cultured astrocytes, either by direct binding of 3H-etorphine or by modulation of cyclic AMP content. These results suggest that endogenous opioid peptides may function indirectly to alter trophic factor synthesis in astrocytes.

Somatostatin content increases following norepinephrine depletion in frontal cortex of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice.

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on somatostatin (SS)-containing neurons were examined by measuring dopamine, norepinephrine (NE), SS, and SS mRNA in striatum and frontal cortex of C57/B16 mice at various times following treatment with MPTP-HCl (96 mg/kg i.p.). MPTP caused a 70% depletion of dopamine in striatum by 1 day and a 40% depletion of NE in frontal cortex within 3 days. SS content was increased in frontal cortex 4 days later, but not in striatum; there were no changes in SS mRNA. Maprotiline, a specific NE-uptake blocker, prevented both the depletion of NE and the increase of SS in frontal cortex due to MPTP administration. These results support the possibility that NE can regulate SS in frontal cortex and are discussed in terms of the decrease of SS seen in parkinsonian patients with dementia.

Renal involvement in POEMS syndrome.

We describe a patient with POEMS syndrome whose renal biopsy specimen also showed nephropathy. Immunoelectron microscopy of the renal biopsy revealed the localization of immunoglobulin (IgA and lambda light chain) in the subendothelial space of the glomerular capillaries, a previously unrecognized finding. We conclude that the renal pathology in POEMS syndrome is unusual and distinct from microangiopathic glomerular involvement or idiopathic mesangiocapillary glomerulonephritis.

Juvenile Sandhoff disease: a Japanese patient carrying a mutation identical to that found earlier in a Canadian patient.

A 35-year-old Japanese man with juvenile Sandhoff disease is described. He showed progressive neurogenic muscular atrophy, cerebellar ataxia and mental deterioration, beginning at age 10 years. The accumulation of GM2 ganglioside in the submucosal nerve cell was confirmed by positive immunostaining using anti-GM2 ganglioside antibody. Biochemical evaluation revealed nearly absent beta-hexosaminidase A and B activities in leukocytes and cultured fibroblasts. Hydrolysis of [3H]globoside I in the intact fibroblasts was apparently disturbed but the rate of hydrolysis was higher than those seen in cells from patients with infantile Sandhoff disease. Analysis of the beta-hexosaminidase beta-subunit gene of the patient disclosed a point mutation (a G-to-A transition) within intron 12. The mutation generates a new splice junction resulting in a 24-base insertion between exons 12 and 13 in the processed mRNA and consequently an 8-amino acid insertion in the translation product. This mutation is identical to that originally found in a Canadian patient with juvenile Sandhoff disease. A possible relationship with the clinical phenotype and the gene abnormality is discussed.

[Two cases of acute coronary occlusion after successful coronary angioplasty associated with a treadmill stress testing].

We presented two cases of acute coronary occlusion after successful percutaneous transluminal coronary angioplasty (PTCA) associated with a treadmill stress testing. Case 1: A 54-year-old man with effort angina was referred to our hospital for cardiac catheterization. At the time of cardiac catheterization, the proximal RCA had a 99% diameter narrowing, and the proximal LCX had a 90% diameter narrowing. PTCA was performed and both lesions were successfully dilated. Eight days after PTCA, he had a symptom-limited treadmill stress testing, using the Bruce protocol. The exercise was terminated at a peak heart rate of 173/min (103% of aged-predicted maximal heart rate), and at a maximal systolic blood pressure of 140 mmHg. A few minutes after the end of exercise, he developed a severe chest pain and ECG changes, which showed ST elevation in leads II, III, aVF and ST depression in leads V4-V6. Emergency coronary angiography disclosed an acute coronary occlusion of RCA at the site of PTCA. Emergency PTCA was performed and the lesion was successfully re-dilated. Case 2: A 68-year-old man was referred to our hospital for cardiac catheterization a month after subendocardial anterior myocardial infarction. At the time of cardiac catheterization, the proximal LAD have a 99% diameter narrowing. PTCA was performed and the lesion was successfully dilated. 18 days after PTCA, he had a symptom-limited treadmill stress testing, using the Bruce protocol. The exercise was terminated at a peak heart rate of 158/min (102% of aged-predicted maximal heart rate), and at a maximal systolic blood pressure of 218 mmHg. Ten minutes after the one of 218 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of juvenile Sandhoff disease].

A Japanese male with juvenile Sandhoff disease is described. The patient was a product of full-term normal pregnancy from non-consanguineous parents. Since age 10, he developed progressive dysarthria and proximal muscle atrophy and weakness. Mental deterioration and cerebellar ataxia are also noted since the age of 20. On neurological examination at age 35, he showed decreased mentality (IQ 62), marked atrophy and weakness of proximal muscles, cerebellar ataxia and increased deep tendon reflexes. Brain CT scans revealed moderate to marked atrophy of cerebellum. Giant MUP, fasciculation potentials and positive sharp waves were observed on EMG examination. Biopsied sural nerve showed markedly decreased myelinated fibers. Hexosaminidase A and B activities in leukocytes and cultured fibroblasts were about 10% of normal values, while other lysosomal enzyme activities were within normal range. Rectal biopsy demonstrated lamellar inclusion bodies in submucosal ganglion cells. This is the first Japanese patient with juvenile Sandhoff disease presenting symptoms similar to motor neuron disease and cerebellar degeneration.

Metabolism of exogenous galactosylceramide in the twitcher mouse brain.

The in vivo metabolism of galactosylceramide (gal-cer) in normal mice and in twitcher mice, a model of human GLD, was examined following intracerebral administration of gal-cer containing [1-14C] stearic acid. In normal mice, gal-cer was hydrolyzed to ceramide within 6 hours and ceramide was hydrolyzed to sphingosine and fatty acid. Most of the released fatty acid was immediately incorporated into other lipids. About 75% of injected gal-cer was hydrolyzed 80 hours after the injection, while in the twitcher mouse, only 17% of gal-cer was hydrolyzed. These results show that degradation of gal-cer is impaired in the twitcher mouse brain, but contradict to the fact that there was no evidence of any accumulation of gal-cer in the brain. This discrepancy may be due to the different sorting routes of biosynthesized and exogenously-administered gal-cer in the mouse brain. Most of the biosynthesized gal-cer is incorporated into myelin, while the injected gal-cer is incorporated into lysosomes.

Biosynthesis of galactosylsphingosine (psychosine) in the twitcher mouse.

In attempts to elucidate the origin of accumulated galactosylsphingosine in the twitcher mouse, a murine model of human globoid cell leukodystrophy (Krabbe's disease), UDP-galactose:sphingosine galactosyltransferase activity was assayed in tissues from normal and twitcher mice. Among several tissues from normal, 20 day postnatal mice, the highest galactosyltransferase activity was found in the brainstem and spinal cord, followed by cerebrum, kidney and liver, in that order. Chronologically, the enzyme activity in the central nervous tissue increased with age, reached a maximum at 25 postnatal days, and declined thereafter. In the kidney and liver, however, the activity remained much the same during development. In the twitcher mouse, developmental change in the enzyme activity was similar to that seen in control mouse, but the decrease in activity in the central nervous tissue after the 25 postnatal days was more rapid. The galactosyltransferase activity and the accumulation of galactosylsphingosine in the tissue of the twitcher mouse were closely related; where and when the enzyme activity was higher, the greater was the accumulation of galactosylsphingosine in the tissue of the twitcher mouse. These results strongly suggest that the accumulated galactosylsphingosine in the twitcher mouse is synthesized mainly by UDP-galactose:sphingosine galactosyltransferase.

Decreased fatty acylation of myelin proteolipid protein in the twitcher mouse.

We examined chronological changes of myelin proteins of the brainstem and spinal cord of the twitcher mouse (15, 20, and 30 days old), a murine model of human globoid cell leukodystrophy caused by a genetic deficiency of galactosylceramidase I activity. The yield of myelin was normal until postnatal day 20, whereas galactosylsphingosine (psychosine) accumulated with age in myelin. The protein profiles of myelin and the activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase in the myelin remained normal throughout the experimental period. Fatty acylation of proteolipid protein (PLP) was examined in a cell-free system by incubation of myelin with [3H]palmitic acid, CoA, and ATP, and was normal at postnatal day 15, but decreased after postnatal day 20. Decreased fatty acylation of PLP was also observed in the twitcher mouse at postnatal day 20 when the isolated myelin was incubated with [14C]palmitoyl-CoA in the absence of ATP and CoA, or the slices of brainstem and spinal cord were incubated with [3H]palmitic acid. The activity of fatty acid:CoA ligase was reduced in myelin. These data suggest that decreased acylation of PLP in twitcher mouse myelin is probably due to reduced activities for both activation and transfer of fatty acid into PLP and that metabolic disturbance is present in myelin because acylation of PLP has been shown to occur in myelin membrane. Although psychosine (200 microM) inhibited only 17% of the acylation in vitro, it may be responsible for the reduced acylation of PLP in vivo.

A high-performance liquid chromatographic assay for acid ceramidase activity in cultured fibroblasts from patients with Farber's disease and from controls.

The high-performance liquid chromatographic (HPLC) method we devised for assay of acid ceramidase activity involves coupling of a fluorescent probe to the enzymatically released sphingosine in the reaction mixture and detection of the fluorescent sphingosine derivative by reverse-phase HPLC. Using the method, acid ceramidase activity in fibroblast homogenates was accurately assayed, with or without the addition of exogenous ceramide, as the substrate, and the patients and carriers of Farber's disease could be readily diagnosed.

Free sphingoid bases in normal murine tissues.

Free sphingoid bases, which have been considered not to occur naturally, were detected in murine tissues by derivatization with o-phthalaldehyde and the use of high-performance liquid chromatography. The concentrations were 10-30 pmol/mg tissue. The lung contained the largest amounts of sphingoid bases. In the molecular species of sphingoid bases, the most abundant was C18-sphingenine followed by C18-sphinganine, 4-hydroxysphinganine and C20-sphingenine, in that order. The central nervous tissues contained relatively high amounts of C20-sphingenine and there was a high concentration of 4-hydroxysphinganine in the kidney. In addition, galactosylsphingenine was detected simultaneously in the spinal cord and sciatic nerve. Sphingoid bases were purified from normal murine lungs using lipid-extraction, cation-exchange and silicic acid column chromatographies, alkaline saponification and preparative thin-layer chromatography. In the purified sphingoid bases, erythro-C18-sphingenine and erythro-C18-sphinganine were identified using thin-layer chromatography, high-performance liquid chromatography and fast-atom-bombardment mass spectrometry. Free sphingoid bases occurring in normal tissues may be metabolic intermediates required for the synthesis or be products of degradation of the sphingolipids and function to regulate cellular metabolism.

Positron emission tomography in cases of chorea with different underlying diseases.

Local cerebral metabolic rate for glucose (LCMRglc) was measured with positron emission tomography using the 18F-fluorodeoxy-glucose method in five patients with chorea due to different underlying diseases. Hypometabolism was observed in the striatum bilaterally in patients with Huntington's disease, choreoacanthocytosis, sporadic progressive chorea and dementia, and pseudo-Huntington form of dentato-rubro-pallido-luysian atrophy (DRPLA). The patient with hemichorea showed hypometabolism in the striatum on the contralateral side to the chorea. The patient with pseudo-Huntington form of DRPLA showed a diffusely decreased LCMRglc in other structures including the cerebral cortex, thalamus and cerebellum. These findings indicated that dysfunction of the striatum is relevant to the genesis of chorea in all these patients, even though the extent of dysfunction in other structures is different in each case.