Cerebellar Blood Flow Research Articles

Flutter-like oscillationを認めた急性小脳炎例

We report herein on our experience in one case of cerebellitis in which the presence of flutter-like oscillation (FLO) helped in the diagnosis and treatment. A 59-year-old man underwent a medical examination for gait impairment. He presented with transient, horizontal and pendular ocular oscillation. This abnormal eye movement was diagnosed as flutter-like oscillation (FLO). The abnormal ocular motion was a characteristic finding in his neuro-otological findings, and although cell counts and protein concentration in his cerebrospinal fluid were significantly elevated, the results of his blood test and brain MRI findings (diffusion-weighted image, Gd-enhanced T1-weighted image) were unremarkable. Brain perfusion scintigraphy revealed modest increase in cerebellar blood flow. After treatment with intravenous immunoglobulin and immunoadsorption therapy, the FLO disappeared. FLO is a rapid abnormal ocular movement to the left and right of the transient lasting for a few seconds. These are important findings when making the diagnosis. FLO has been reported to be mostly due to a cerebellar deficit. Cerebellitis is a disease that is mainly associated with trunk ataxia, poor coordination of the extremities, dysarthria, and abnormal ocular movements. In many cases, cerebellitis is preceded by symptoms of infection symptoms preceding, but many cases have also been reported where such symptoms are unclear. As for the pathogenesis of cerebellitis, direct bacterial and viral infection, a post-infection-associated immunological mechanism of and activation of a subclinical virus have all been considered. We could not find any obvious signs of a preceding infection in our case and various virus antibodies were also negative. Although the findings of protein cell dissociation were recognized in the cerebrospinal fluid examination carried out as one of the assessments, the cerebellitis in this patient was identified by immunologically. Our results suggested that a diagnosis of cerebellitis could be important for the observation of ocular movement.

Combined Measurement of Cerebral and Cerebellar Blood Flow on Preoperative Brain Perfusion SPECT Imaging Predicts Development of New Cerebral Ischemic Events After Endarterectomy for Symptomatic Unilateral Cervical Carotid Stenosis

The aim of this study was to determine whether the ratio of blood flow contralateral-to-affected asymmetry in the cerebellar hemisphere to blood flow affected-to-contralateral asymmetry in the middle cerebral artery (MCA) territory (AR(cbl)/AR(MCA)) on preoperative brain perfusion SPECT could identify patients at risk for new cerebral ischemic events after carotid endarterectomy (CEA) for symptomatic unilateral cervical carotid stenosis. For the purposes of this study, new cerebral ischemic events included neurological deficits and cerebral ischemic lesions on diffusion-weighted MRI. Brain blood flow was assessed using 123I-IMP SPECT in 101 patients. A region of interest was automatically placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres using a 3-dimensional stereotaxic region-of-interest template, and the AR(cbl)/AR(MCA) was calculated. Diffusion-weighted MRI was performed within 3 days before and 24 hours after surgery. Patients were neurologically tested before induction of general anesthesia and after recovery from general anesthesia. New cerebral ischemic events after CEA were observed in 12 patients (12%). Multivariate analysis revealed that only high AR(cbl)/AR(MCA) was significantly associated with the development of new postoperative cerebral ischemic events (95% confidence interval, 1.945-8.452; P = 0.0070). The AR(cbl)/AR(MCA) provided 75% sensitivity, 84% specificity, and 39% positive and 96% negative predictive values in predicting development of new postoperative cerebral ischemic events. The AR(cbl)/AR(MCA) on preoperative brain perfusion SPECT could identify patients at risk for new cerebral ischemic events after CEA for unilateral cervical carotid stenosis.

Hemodynamic changes during neural deactivation in awake mice: A measurement by laser-Doppler flowmetry in crossed cerebellar diaschisis

Crossed cerebellar diaschisis (CCD) caused by contralateral supratentorial lesions can be considered a condition of neural deactivation, and hemodynamic changes in CCD were investigated with positron emission tomography (PET) in humans. In the present study, to investigate the effects of neural deactivation on hemodynamics, we developed a new mouse model of CCD, which was caused by middle cerebral artery occlusion (MCAO), and measured changes in cerebellar blood flow (CbBF), red blood cell (RBC) velocity and concentration due to CCD using laser-Doppler flowmetry (LDF) in awake mice. The ratio of the CCD side to the unaffected side in the cerebellum for CbBF 1 day after MCAO was decreased by −18% compared to baseline (before CCD). The ratio of the CCD side to the unaffected side for RBC concentration 1 day after MCAO was decreased by −23% compared to baseline. However, no significant changes in the ratio of the CCD side to the unaffected side were observed for RBC velocity. The present results indicate that the reduction of CbBF induced by neural deactivation was mainly caused by the decrease in RBC concentration. In contrast, our previous study showed that RBC velocity had a dominant role in the increase in cerebral blood flow (CBF) induced by neural activation. If RBC concentration can be considered an indicator of cerebral blood volume (CBV), hemodynamic changes due to neural activation and deactivation measured by LDF in mice might be in good agreement with human PET studies.

Cerebellar and Cerebral Autoregulation in Migraine

Silent ischemic brain lesions frequently occur in migraine with aura and are most often located in cerebellar border zones. This may imply an impairment of cerebellar blood flow autoregulation. This study investigated the characteristics of interictal cerebellar autoregulation in migraine with and without aura. Thirty-four patients (n=17, migraine without aura; n=17, migraine with aura) and 35 age- and sex-matched controls were studied. Triple simultaneous transcranial Doppler monitoring of one posterior inferior cerebellar artery, right posterior cerebral artery, and left middle cerebral artery was performed. Autoregulation dynamics were assessed from spontaneous blood pressure fluctuations (correlation coefficient index Dx) and from respiratory-induced 0.1-Hz blood pressure oscillations (phase and gain). Compared with controls, the autoregulatory index Dx was higher (indicating less autoregulation) in the posterior inferior cerebellar artery (P=0.0062) and middle cerebral artery (P=0.0078) in migraine with aura, but not in migraine without aura. Phase and gain did not significantly differ between migraine patients and controls. No significant associations of autoregulation with clinical factors were found, including frequency of migraine attacks and orthostatic intolerance. This first-time analysis of cerebellar autoregulation in migraine did not show a specific cerebellar dysautoregulation in the interictal period. More static autoregulatory properties (index Dx) are, however, impaired in persons with migraine with aura both in the cerebellar and anterior circulation. The cerebellar predilection of ischemic lesions in migraine with aura might be a combination of altered autoregulation and additional factors, such as the end artery cerebellar angioarchitecture.

Cerebellar and lobar blood flow in schizophrenia: A perfusion weighted imaging study

It is still not clear whether brain hemodynamics plays a role in the functional and structural alterations in schizophrenia, since prior imaging studies showed conflicting findings. In this study we non-invasively explored cerebral and cerebellar lobe perfusion in the largest population of participants with schizophrenia thus far studied with perfusion-weighted imaging (PWI). Forty-seven participants affected by schizophrenia and 29 normal controls were recruited. PWI images were acquired following the intravenous injection of a paramagnetic contrast agent. Regional cerebral blood volume (CBV), blood flow (rCBF), and mean transit time (MTT) were obtained with the block-Circulant Singular Value Decomposition (cSVD) for frontal, temporal, parietal, occipital, and cerebellar lobes, bilaterally. Perfusion parameters were separately obtained for both gray and white matter in each lobe. Subjects with schizophrenia showed no significant differences in perfusion parameters when compared with controls. Interestingly, inverse correlations between age at onset and occipital, frontal and cerebellar MTT and between length of illness and frontal CBV were found. Preserved cerebral and cerebellar perfusion in our chronic population may in part be due to the effects of antipsychotic treatment which may have normalized blood volume and flow. Hypoperfusion in relation to chronicity, particularly in the frontal lobe, has been observed in accordance with earlier studies using positron emission tomography.

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). Seven patients with MSA-C received TRH intravenously (2 mg/day) for 14 days. Clinical efficacy was assessed using the International Cooperative Ataxia Rating Scale (ICARS) and brain perfusion single photon emission-computed tomography was performed before and after therapy. The rCBF in each region of interest (ROI) was calculated using 3DSRT, a fully automated the ROI technique. The ICARS scores slightly improved in 6 of the 7 patients after TRH therapy, but this was not statistically significant. After TRH therapy, the cerebellar rCBF reduced in the 6 of 7 patients and the mean rCBF in cerebellum also significantly decreased (P=0.029, paired t-test), whereas the rCBF in the precentral segment tend to increase (P=0.048, paired t-test). TRH therapy may be less effective on cerebellar ataxia and cerebellar rCBF in MSA-C. The 3DSRT program may be useful for the evaluation of the efficacy of TRH therapy on cerebral blood flow.

Selective loss of Purkinje cells in a patient with anti-gliadin-antibody-positive autoimmune cerebellar ataxia

The patient was an 84-year-old woman who had the onset of truncal ataxia at age 77 and a history of Basedow's disease. Her ataxic gait gradually deteriorated. She could not walk without support at age 81 and she was admitted to our hospital at age 83. Gaze-evoked nystagmus and dysarthria were observed. Mild ataxia was observed in all limbs. Her deep tendon reflex and sense of position were normal. IgA anti-gliadin antibody, IgG anti-gliadin antibody, anti-SS-A/Ro antibody, anti-SS-B/La antibody and anti-TPO antibody were positive. A conventional brain MRI did not show obvious cerebellar atrophy. However, MRI voxel based morphometry (VBM) and SPECT-eZIS revealed cortical cerebellar atrophy and reduced cerebellar blood flow. IVIg treatment was performed and was moderately effective. After her death at age 85, the patient was autopsied. Neuropathological findings were as follows: selective loss of Purkinje cells; no apparent degenerative change in the efferent pathways, such as the dentate nuclei or vestibular nuclei; no prominent inflammatory reaction. From these findings, we diagnosed this case as autoimmune cerebellar atrophy associated with gluten ataxia. All 3 autopsies previously reported on gluten ataxia have noted infiltration of inflammatory cells in the cerebellum.In this case, we postulated that the infiltration of inflammatory cells was not found because the patient's condition was based on humoral immunity. The clinical conditions of gluten ataxia have not yet been properly elucidated, but are expected to be revealed as the number of autopsied cases increases.

025 Crossed cerebellar diaschisis: assessment with dynamic contrast imaging on whole brain perfusion on 320 slice CT scanner

Purpose: Crossed cerebellar diaschisis refers to metabolic depression in the cerebellum contralateral to supratentorial lesions. It was first described in the positron emission tomography (PET) literature. Crossed cerebellar diaschisis is...

Crossed cerebellar diaschisis in intracarotid sodium amytal procedures: a SPECT study

Eight patients with drug-resistant complex-partial seizures were subjected to left- and right-sided intracarotid sodium amytal (ISA) procedures during preoperative investigations for surgical treatment. Regional changes of cerebral and cerebellar blood flow during barbiturization were measured by [99mTc]-HMPAO-SPECT. Crossed cerebellar diaschisis (CCD) was observed in 13 out of 16 tests (81%) as well as ipsilateral cerebral hypoperfusion (87%). Thus CCD occurred more frequently in ISA procedures than in previously studied patients with cerebral infarctions and tumors. Since intracarotid injections of sodium amytal lead to hypoperfusion mainly in those areas of the brain that are supplied by the middle cerebral artery, functional suppression of these regions is supposed to be one of the main preconditions of CCD. Our findings suggest that CCD as demonstrated by the SPECT-technique is a common phenomenon in ISA procedures.

Regional cerebral blood flow in chronic alcoholics measured by single photon emission computerized tomography

Regional cerebral blood flow (CBF) was measured by single photon emission computerized tomography of inhaled 133-Xe in 20 chronic alcoholic men. Mean CBF was 51 ml/(100 g x min) compared with 53 ml/(100 g x min) in 20 normals. Reduced cerebellar blood flow correlated both to structural abnormalities seen on CT scan and to cognitive dysfunction. Slight abnormalities of the regional CBF was observed in the alcoholics. They had a higher incidence of regional low flow areas than a control group. Low flow areas were found in frontal and posterior parts of the brain not only in patients with atrophia, but also in patients without CT abnormalities, suggesting neuronal dysfunction. The occurrence of regional low flow areas was associated with the severity of alcoholism, cerebral atrophy and intellectual impairment.

重症熱中症急性期にＭＲＩ拡散強調像にて小脳皮質の高信号を捉えた１例

A 47-year-old man was admitted to the hospital because of general convulsion, loss of consciousness and hyperthermia. A diagnosis of acute heat stroke was made clinically and neuroradiologically. As the consciousness level ameliorated, he developed severe abulia and mutism, then cerebellar ataxic syndrome (viz. truncal ataxia, hypermetria, ataxic speech and nystagmus). An MRI (diffusion weighted image; DWI) disclosed abnormal diffuse high signal intensity of the cerebellar cortex with reduced apparent diffusion coefficient (ADC). Two months later after the onset, truncal ataxia and dysarthria significantly improved, while dysmetria of the extremities rather worsened. At that time, the abnormal signal intensity of the cerebellar cortex disappeared, and the cerebellum became atrophic. The cerebellar blood flow was significantly decreased on brain SPECT (99mTc-ECD). The abnormal DWI signal intensity of the cerebellar cortex in the present patient may represent the cytotoxic edema of Purkinje cells resulting from heat stroke-related hyperthermia It is essential to repeat MRI examination for cerebellar pathology and to obtain better insight into sequelae in patients with acute heat stroke. Protirelin tartrate seemed to be valid for improvement of abulia in the present patient. Further study is indicated.

Cerebellar Autoregulation Dynamics in Humans

Knowledge on autoregulation of cerebellar blood flow in humans is scarce. This study investigated whether cerebellar autoregulation dynamics and CO(2) reactivity differ from those of the supratentorial circulation. In 56 healthy young adults, transcranial Doppler (TCD) monitoring of the posterior inferior cerebellar artery (PICA) and, simultaneously, of the contralateral middle cerebral artery (MCA) was performed. Autoregulation dynamics were assessed by the correlation coefficient method (indices Dx and Mx) from spontaneous blood pressure fluctuations and by transfer function analysis (phase and gain) from respiratory-induced 0.1 Hz blood pressure oscillations. CO(2) reactivity was measured via inhalation of air mixed with 7% CO(2). The autoregulatory indices Dx and Mx did not differ between the cerebellar (PICA) and cerebral (MCA) vasculature. Phase and gain, which describe faster aspects of autoregulation, showed slightly better values in the PICA compared with the MCA (higher phase, P=0.005; lower gain, P=0.007). Correlation between absolute autoregulation values in the PICA and the MCA was significant (P<0.001). The TCD CO(2) reactivity was significantly lower in the PICA (P<0.001), which could be influenced by an assumed PICA dilation under hypercapnia. In conclusion, dynamic autoregulation in the human cerebellum is well operating and has slightly faster regulatory properties than the anterior cerebral circulation.

Gamma-Aminobutyric Acid Modulates Local Brain Oxygen Consumption and Blood Flow in Rat Cerebellar Cortex

In the awake brain, the global metabolic rate of oxygen consumption is largely constant, while variations exist between regions dependent on the ongoing activity. This suggests that control mechanisms related to activity, that is, neuronal signaling, may redistribute metabolism in favor of active networks. This study examined the influence of gamma-aminobutyric acid (GABA) tone on local increases in cerebellar metabolic rate of oxygen (CeMR(O(2))) evoked by stimulation of the excitatory, glutamatergic climbing fiber-Purkinje cell synapse in rat cerebellum. In this network, the postsynaptic depolarization produced by synaptic excitation is preserved despite variations in GABAergic tone. Climbing fiber stimulation induced frequency-dependent increases in synaptic activity and CeMR(O(2)) under control conditions. Topical application of the GABA(A) receptor agonist muscimol blocked the increase in CeMR(O(2)) evoked by synaptic excitation concomitant with attenuation of cerebellar blood flow (CeBF) responses. The effect was reversed by the GABA(A) receptor antagonist bicuculline, which also reversed the effect of muscimol on synaptic activity and CeBF. Climbing fiber stimulation during bicuculline application alone produced a delayed undershoot in CeBF concomitant with a prolonged rise in CeMR(O(2)). The findings are consistent with the hypothesis that activity-dependent rises in CeBF and CeMR(O(2)) are controlled by a common feed-forward pathway and provide evidence for modification of cerebral blood flow and CMR(O(2)) by GABA.

Poster 14: Disturbance of Cerebellar Blood Flow on Postural Sway in Patients With Cerebrovascular Attack

Poster 14: Disturbance of Cerebellar Blood Flow on Postural Sway in Patients With Cerebrovascular Attack

A case of cerebellar infarction caused by vertebral artery injury from a stab wound to the neck

Vertebral artery injuries are the least common arterial injuries because of the deep location of the vessel in a bony canal. Injury of this vessel has not been associated with neurological deficits, and it is thought that many of these injuries are not recognized. The incidence of vertebral artery injury occurring after a penetration wound to the neck varies from 1.0% in gunshot wounds to 7.4% in stab wounds. However, even with vertebral artery injury in penetration wounds of the neck the association with cerebellar infarction is a rare occurrence. We describe a case of cerebellar infarction caused by vertebral artery injury from a stab wound that severed the vessel between the transverse processes of C3 and C4 with a hypoplastic contralateral vertebral artery. The patient ultimately suffered infarction of the cerebellum due to the lack of preservation of the posterior inferior cerebellar artery blood flow. Management is discussed and the medical literature is reviewed.

Reventilation with room air or 100% oxygen after asphyxia differentially affects cerebral neuropathology in newborn pigs

To test if reventilation with room air (RA) or 100% oxygen (O2) after asphyxia would differentially affect neuronal damage in different brain areas of newborn pigs. Anaesthetized piglets were subjected to 10 min asphyxia (n=27) or served as time controls (n=7). Reventilation started with either RA or O2 for 1 h, and was continued with RA for an additional 1-3 h. Cortical or cerebellar blood flow was assessed with laser-Doppler flowmetry (LDF). Haematoxylin/eosin-stained sections from six brain regions were prepared for blinded neuropathological examination and scoring. Asphyxia resulted in significant neuronal damage compared to time controls in all areas examined except the pons. O2 ventilation elicited greater neuronal lesions in the hippocampus and the cerebellum but smaller damage in the basal ganglia compared to RA. The assessed physiological parameters including the LDF signals were similar in both ventilation groups, except for PaO2 in the first hour of reventilation (RA 75+/-5 mmHg, O2 348+/-57 mmHg; p<0.05). Interestingly, however, reactive hyperaemia was much higher in the O2-sensitive cerebellum as compared with the cortex (1101+/-227 vs 571+/-73; p<0.05, area under the curve). O2 toxicity after asphyxia was demonstrated in the piglet hippocampus and cerebellum but not in the cerebral cortex or basal ganglia. The observed regional differences may be associated with local haemodynamic factors.

Mutation analysis of the ATM gene in two Chinese patients with ataxia telangiectasia

Ataxia telangiectasia (A–T) is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectasia, immunodeficiency, elevated α-fetoprotein level, chromosomal instability, predisposition to cancer, and radiation sensitivity. Although a lot of mutations in the ATM gene have been described, there is still no report about ATM mutations in Chinese population. Using a molecular approach, we screened for ATM mutations in two patients from two unrelated Chinese families. 100 normal controls were analyzed to exclude possibility of polymorphism. Two novel mutations in the ATM gene were identified. The first one is a novel, homozygous, 1346G > C (Gly449Ala) missense mutation. The second one is a compound heterozygous mutation, which consists of a novel, 610G > T (Gly204Stop) nonsense mutation, combined with a previously reported, 6679C > T (Arg2227Cys) missense mutation. The transversions 1346G > C (Gly449Ala) and 610G > T (Gly204Stop) are not localized either in the conserved PI-3 kinase domain or in the other domains of the ATM protein. The phenotypic features were characterized by progressive cerebellar ataxia, ocular telangiectasia, elevated α-fetoprotein level, immunodeficiency (agammaglo–bulinemia and T-cell defect), and rearrangements of chromosomes 7 and 14; brain MRI showed cerebellar atrophy, brain SPECT showed cerebellar regional cerebral blood flow (rCBF) hypoperfusion. To our knowledge, this is the first report of ATM mutations in Mainland China, in which the transversions 1346G > C (Gly449Ala) and 610G > T (Gly204Stop) are two novel, disease-causing mutations.

Combined measurements of cerebellar blood flow, local field potentials and glucose utilization during climbing fibres stimulation: Effect of postsynaptic excitatory activity

Combined measurements of cerebellar blood flow, local field potentials and glucose utilization during climbing fibres stimulation: Effect of postsynaptic excitatory activity

Research on clinical characteristics and ATM gene mutations in Chinese patients with ataxia-telangiectasia

To investigate the clinical manifestation and mutation characteristics of ATM gene in Chinese patients with ataxia-telangiectasia (AT). Sequence variants of the entire coding exons of ATM gene were tested using polymerase chain reaction (PCR), reverse transcription-polymerase chain reaction (RT-PCR), polyacrylamide gel electrophoresis (PAGE) and DNA direct sequencing in two Chinese patients clinically diagnosed as AT. The clinical characteristics of two AT patients were progressive cerebellar ataxia with ages at onset of childhood, ocular-cutaneous telangiectasia and recurrent pulmonary infection due to immuno-deficiency; the serum alpha fetoprotein (AFP) levels were higher than normal, the serum immunoglobin IgA and IgG levels were lower than normal; brain MRI showed cerebellar atrophy, brain SPECT showed cerebellar regional cerebral blood flow (rCBF) hypoperfusion to a certain degree. Totally three nucleotide changes were identified. A missense mutation of G1346C in exon 11, which was a homozygotic mutation, was identified in one patient; a nonsense mutation of G610T in exon 6 combined with a missense mutation of C6679T in exon 47, which was a compound heterozygotic mutation, were identified in the other patient. They were co-segregated with the disease and were localized within the functional domain of ATM gene. We have made gene diagnoses for two Chinese AT patients, in which three novel ATM gene mutations were identified.

Influence of Repetitive Transcranial Magnetic Stimulation on Disease Severity and Oxidative Stress Markers in the Cerebrospinal Fluid Of Patients with Spinocerebellar Degeneration

Ataxia severity, cerebellar hemispheric blood flow (CHBF), ascorbate free radical (AFR), superoxide dismutase protein, superoxide scavenging activity, and 8–hydroxy–2´–deoxyguanosine (8–OHdG) in cerebrospinal fluid (CSF) were compared before and after an 8–week course of repetitive transcranial magnetic stimulation (rTMS) in 20 patients with spinocerebellar degenerations (SCD). SCD patients showed higher AFR, 8–OHdG, and superoxide scavenging activity than 19 controls. In SCD patients, AFR and ataxia severity declined, and CHBF increased after rTMS. As the SCD patients showed negative correlations between ataxia severity and CHBF or superoxide scavenging activity, the therapeutic mechanism of rTMS may involve decreased oxidative stress and increased CHBF.