Republished: A novel combined approach using a Penumbra catheter and balloon catheter for cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis is sometimes fatal. We describe a case of sinus thrombosis in a 43-year-old woman presenting with generalized seizure, delirium, and a 2 week history of headache and nausea. The patient underwent mechanical thrombectomy using a novel combined approach, in which a Shouryu HR balloon catheter (Kaneka) was anchored in the right transverse sinus (TS), sigmoid sinus (SS), and superior sagittal sinus (SSS), while a Penumbra 5 MAX ACE (Penumbra) catheter was moved back and forth between the right TS, SS, and SSS. Additionally, back and forth movement of the inflated balloon with aspiration-the so-called 'dental floss technique'-was performed. Partial recanalization was eventually obtained. Follow-up angiography on postoperative day 7 showed a dramatic improvement in venous outflow. The patient was transferred to a rehabilitation hospital on postoperative day 42. We describe our combined approach using aspiration, and Penumbra and balloon catheters, to achieve mechanical thrombectomy for sinus thrombosis.

A novel combined approach using a Penumbra catheter and balloon catheter for cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis is sometimes fatal. We describe a case of sinus thrombosis in a 43-year-old woman presenting with generalized seizure, delirium, and a 2 week history of headache and nausea. The patient underwent mechanical thrombectomy using a novel combined approach, in which a Shouryu HR balloon catheter (Kaneka) was anchored in the right transverse sinus (TS), sigmoid sinus (SS), and superior sagittal sinus (SSS), while a Penumbra 5 MAX ACE (Penumbra) catheter was moved back and forth between the right TS, SS, and SSS. Additionally, back and forth movement of the inflated balloon with aspiration-the so-called 'dental floss technique'-was performed. Partial recanalization was eventually obtained. Follow-up angiography on postoperative day 7 showed a dramatic improvement in venous outflow. The patient was transferred to a rehabilitation hospital on postoperative day 42. We describe our combined approach using aspiration, and Penumbra and balloon catheters, to achieve mechanical thrombectomy for sinus thrombosis.

Reduced pallidal output causes dystonia.

Dystonia is a neurological disorder characterized by sustained or repetitive involuntary muscle contractions and abnormal postures. In the present article, we will introduce our recent electrophysiological studies in hyperkinetic transgenic mice generated as a model of DYT1 dystonia and in a human cervical dystonia patient, and discuss the pathophysiology of dystonia on the basis of these electrophysiological findings. Recording of neuronal activity in the awake state of DYT1 dystonia model mice revealed reduced spontaneous activity with bursts and pauses in both internal (GPi) and external (GPe) segments of the globus pallidus. Electrical stimulation of the primary motor cortex evoked responses composed of excitation and subsequent long-lasting inhibition, the latter of which was never observed in normal mice. In addition, somatotopic arrangements were disorganized in the GPi and GPe of dystonia model mice. In a human cervical dystonia patient, electrical stimulation of the primary motor cortex evoked similar long-lasting inhibition in the GPi and GPe. Thus, reduced GPi output may cause increased thalamic and cortical activity, resulting in the involuntary movements observed in dystonia.

Cortically evoked responses of human pallidal neurons recorded during stereotactic neurosurgery.

Responses of neurons in the globus pallidus (GP) to cortical stimulation were recorded for the first time in humans. We performed microelectrode recordings of GP neurons in 10 Parkinson's disease (PD) patients and 1 cervical dystonia (CD) patient during surgeries to implant bilateral deep brain stimulation electrodes in the GP. To identify the motor territories in the external (GPe) and internal (GPi) segments of the GP, unitary responses evoked by stimulation of the primary motor cortex were observed by constructing peristimulus time histograms. Neurons in the motor territories of the GPe and GPi responded to cortical stimulation. Response patterns observed in the PD patients were combinations of an early excitation, an inhibition, and a late excitation. In addition, in the CD patient, a long-lasting inhibition was prominent, suggesting increased activity along the cortico-striato-GPe/GPi pathways. The firing rates of GPe and GPi neurons in the CD patient were lower than those in the PD patients. Many GPe and GPi neurons of the PD and CD patients showed burst or oscillatory burst activity. Effective cathodal contacts tended to be located close to the responding neurons. Such unitary responses induced by cortical stimulation may be of use to target motor territories of the GP for stereotactic functional neurosurgery. Future findings utilizing this method may give us new insights into understanding the pathophysiology of movement disorders.

Endovascular recanalization of the completely occluded internal carotid artery using a flow reversal system at the subacute to chronic stage.

OBJECT: The efficacy and pitfalls of endovascular recanalization were evaluated in cases of internal carotid artery (ICA) occlusion in the subacute to chronic stage. METHODS: Fourteen cases (15 lesions) of symptomatic ICA occlusion with hemodynamic compromise or recurrent symptoms were treated at the subacute to chronic stage using an endovascular technique. The Parodi embolic protection system was used during the recanalization procedure to prevent embolic stroke by reversing the flow from the distal ICA to the common carotid artery. RESULTS: Recanalization of the occluded ICA was possible in 14 of 15 lesions. The occlusion points were 10 cervical ICAs and 4 petrous/cavernous ICAs in successfully recanalized cases. Ischemic symptoms disappeared completely after the treatment, and new ischemic symptoms did not appear related to the treated lesion. Single photon emission computed tomography findings demonstrated the improvement of hemodynamic compromise in all cases. One case showed right middle cerebral artery branch occlusion during the procedure, but this patient's neurological symptoms were stable due to preexisting hemiparesis. Endovascular recanalization was possible and effective in improving hemodynamic compromise. However, there are still several problems with this technique, such as hyperperfusion syndrome after recanalization, cerebral embolism during treatment, durability after treatment, and identification of the occlusion point before treatment. CONCLUSIONS: Endovascular recanalization using an embolic protection device can be considered as an alternative treatment for symptomatic ICA occlusion with hemodynamic compromise or refractoriness to antiplatelet therapy, even in the subacute to chronic stage of the illness.

Generation of dopamine neurons from embryonic stem cells in the presence of the neuralizing activity of bone marrow stromal cells derived from adult mice.

Stromal cell lines such as PA6 and MS5 have been employed for generating dopamine (DA) neurons from embryonic stem (ES) cells. The present study was designed to test whether bone marrow stromal cells (BMSC) derived from adult mice might be available as a feeder layer to produce DA cells efficiently from ES cells. When ES cells were grown on BMSC in the presence of fibroblast growth factor 8 (FGF8) and sonic hedgehog (SHH), about 40% of TuJ1-positive neurons expressed tyrosine hydroxylase (TH). Because these cells labeled with TH were negative for dopamine-beta-hydroxylasae (DBH), the marker for noradrenergic and adrenergic neurons, the TH-positive cells were most likely DA neurons. They indeed expressed midbrain DA neuron markers such as Nurr 1, Ptx-3, and c-ret and were capable of synthesizing and releasing DA in vitro. Furthermore, DA neurons differentiated from ES cells in this differentiation protocol survived transplantation in rats with 6-hydroxydopamine lesions and reversed the lesion-induced circling behavior. The data indicate that BMSC can facilitate an efficient induction of DA neurons from ES cells and that the generated DA neurons are biologically functional both in vitro and in vivo. Insofar as BMSC have recently been employed in autologous cell therapy for ischemic heart and arteriosclerotic limb diseases, the present study raises the possibility that autologous BMSC can be applied in future cell transplantation therapy in Parkinson's disease.

Protection of dopamine neurons by bone marrow stromal cells.

Transplantation of bone marrow stromal cells (BMSC) has recently been demonstrated to provide neuroprotection in animal models of brain injuries such as ischemia and trauma. The present study was undertaken to explore whether BMSC can promote the survival of dopamine (DA) neurons in neuronal insult models in vitro. We also examined whether BMSC can increase the survival rate of embryonic DA neurons grafted into the striatum of a rat model of Parkinson's disease (PD). Treatment with conditioned media derived from BMSC cultures was found to significantly prevent the death of DA neurons in in vitro cell injury models such as serum deprivation and exposure to the neurotoxin 6-OHDA. In a transplantation study, we also found that the survival of grafted DA cells was significantly enhanced by treating donor cells with the conditioned media at the steps of both cell dissociation and implantation. The results suggest that BMSC may secrete diffusible factors able to protect DA neurons against neuronal injuries. Indeed, BMSC expressed mRNA encoding brain-derived neurotrophic factor, fibroblast growth factor-2 and glial cell line-derived neurotrophic factor, all of which have previously been shown to exhibit potent neurotrophic effects on DA cells. Enzyme-linked immunosorbent assay revealed that the cells release these growth factors into culture media. The present data indicate that BMSC may be a potential donor source of cell-based regenerative therapy for PD where the progressive loss of the midbrain DA neurons takes place.

Transplantation of autologous sympathetic neurons as a potential strategy to restore metabolic functions of the damaged nigrostriatal dopamine nerve terminals in Parkinson's disease.

Grafting of catecholamine-producing cells can be a possible therapeutic strategy for attenuating motor symptoms in Parkinson's disease (PD). The potential of autologous sympathetic neurons has been investigated as a donor for cell therapy of PD. The clinical trials of autotransplantation of sympathetic ganglion cells in PD have revealed that the grafts increase the duration of L-DOPA (L-dihydroxy phenyl alanine)-induced beneficial effects, and that the graft-mediated effect is detectable during a follow-up period of at least 1 year postgrafting. In an in vitro analysis of the ability of human sympathetic neurons to release catecholamines, although DA was not detectable under basal conditions, DA levels were significantly increased upon exposure to exogenous L-DOPA. Furthermore, animal experiments with xenografting of human sympathetic ganglionic neurons in the DA-denervated striatum of rats demonstrated that a significant increase in striatal DA levels is noted after systemic L-DOPA treatment, and that the DA levels remain high for longer periods of time in the grafted rats than in control animals with sham surgery. The L-DOPA-induced rise of striatal DA levels was significantly attenuated when given reserpine pretreatment. This suggests that DA derived from exogenously administered L-DOPA is subjected to, at least in part, vesicular storage in grafted sympathetic neurons. Histological examinations indeed showed that the grafts express aromatic-L-amino acid decarboxylase and vesicular monoamine transporter-2, both of which are important molecules for the synthesis and the storage of DA, respectively. Taken together, grafted sympathetic neurons can provide a site for both the conversion of exogenous L-DOPA to DA and the storage of the synthesized DA in the DA-denervated striatum. This might be an explanation for a mechanism by which sympathetic neuron autografts can increase the duration of L-DOPA effects in PD patients. This review article summarizes the clinical effect of transplantation of autologous sympathetic neurons in PD and discusses the underlying mechanism for the effect based on experimental evidence previously obtained.

Usefulness of a cube-copying test in outpatients with dementia.

OBJECTIVE: To clarify whether a quantitatively scored cube-copying test could rapidly assess dementia patients, predicting thier performance in cognitive tests. METHODS: Subjects were 171 outpatients with amnesia who were including 92 with Alzheimer's disease (AD); 59 vascular dementia (VD); 17 frontotemporal dementia (FTD); and three lewy body disease (DLB) and 32 normal healthy subjects. Subjects asked to copy a perspective drawing of a cube. Points of connection and plane-orientation errors were scored using Maeshima's method. The Mini-Mental State Examination (MMSE), an auditory verbal learning test (AVLT), a word fluency test and Raven's Coloured Progressive Matrices (RCPM) were administered. Age, clinical disease severity, symptom duration, specific diagnosis and neuropsychological scores were evaluated for relationships with constructional ability. RESULTS: The cube-copying test showed errors in most dementia patients and 11 of 32 normal subjects. Only three patients each with AD and VD copied correctly, but 11 patients with 17 FTD drew the cube correctly. Numbers of connections completed and plane-orientation errors correlated significantly with MMSE, AVLT, word fluency and RCPM scores. CONCLUSION: The cube-copying test is useful for routine clinical dementia screening, however the test examines only one aspect of cognitive function. While not an alternative to conventional neuropsychological examinations, quantitatively scored cube copying can provide a rough estimate of cognitive dysfunction in dementia patients.

The ability of grafted human sympathetic neurons to synthesize and store dopamine: a potential mechanism for the clinical effect of sympathetic neuron autografts in patients with Parkinson's disease.

We have investigated the potential of autologous sympathetic neurons as a donor for cell therapy of Parkinson's disease (PD). Our recent study demonstrated that sympathetic neuron autografts increase the duration of levodopa-induced "on" periods with consequent reduction in the percent time spent in "off" phase. We also found that human sympathetic neurons grown in culture have the ability to convert exogenous levodopa to dopamine and to store the synthesized dopamine. This may explain the clinically observed prolongation in the duration of levodopa effects. To further analyze the mechanism for the graft-mediated effect, the present study investigated the metabolic function of human sympathetic ganglionic neurons xenografted into the dopamine (DA)-denervated striatum of rats by monitoring striatal levels of DA and its primary metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), after systemic administration of levodopa. We also explored whether the graft-mediated effect above may last in four PD patients who had been given the grafts and followed for 12-36 months postgrafting. Clinical evaluations showed that an increase in the duration of levodopa-induced "on" phase is detected during a follow-up period of 12-36 months postgrafting in all the four patients tested. Accordingly, the percent time spent in "off" phase exhibited a 30-40% reduction as compared to the pregrafting values. The animal experiment showed that a significant increase in striatal DA levels is noted after systemic levodopa treatment, and that the DA levels remain high for longer periods of time in the grafted rats than in control animals. When given reserpine pretreatment, the levodopa-induced rise of striatal DA levels was significantly attenuated with concomitant increase in DOPAC levels. Histological examinations demonstrated that the grafts contain some tyrosine hydroxylase (TH)-positive cells. These cells were also found to express aromatic-l-amino acid decarboxylase (AADC) and vesicular monoamine transporter-2 (VMAT), both of which are important molecules for the synthesis and the storage of DA, respectively. These results indicate that grafted sympathetic neurons can provide a site for both the conversion of exogenous levodopa to DA and the storage of the synthesized DA in the DA-denervated striatum, explaining a mechanism by which sympathetic neuron autografts can increase the duration of levodopa-induced "on" phase in PD patients.

Relationship between cognitive function and regional cerebral blood flow in different types of dementia.

PURPOSE: We assessed relationships between cognitive impairment and regional cerebral blood flow (rCBF) in the different types of dementia. SUBJECTS AND METHODS: Subjects, who included 27 with Alzheimer's disease (AD), seven with frontotemporal dementia (FTD), six with vascular dementia (VaD), and 12 normal controls, were evaluated using the Mini-mental State (MMS), Kana-hiroi Test, an auditory verbal learning test (AVLT), a word fluency test (WFT) and Raven's Coloured Progressive Matrices (RCPM). The rCBF was measured using a three-dimensional stereotaxic ROI template method (3DSRT). RESULTS: In all dementia types, left superior frontal hypoperfusion was demonstrated. In AD and VaD significant CBF reduction also was seen in both angular, temporal, occipital, and precentral, both hippocampi, thalami, and pericallosal regions, and the left lenticular nucleus. MMS, Kana-hiroi Test, and AVLT scores correlated with CBF in all regions. WFT scores were correlated highly with CBF in the left side in frontal, temporal, and angular regions and right and left lenticular nuclei, thalami, and pericallosal regions. RCPM scores correlated with CBF in posterior regions. CONCLUSION: Close coupling was evident between reduced rCBF and cognitive dysfunction in patients with dementia. Use of neuropsychologic tests and rCBF determinations in combination should enhance diagnostic accuracy.

Implantation of human amniotic epithelial cells prevents the degeneration of nigral dopamine neurons in rats with 6-hydroxydopamine lesions.

We recently found that human amniotic epithelial (HAE) cells secrete biologically active neurotrophins such as brain-derived neurotrophic factor and neurotrophin-3, both of which exhibit trophic activities on dopamine (DA) neurons. The present study explored whether implantation of HAE cells can be a possible means to deliver trophic factors into the brain to prevent the death of DA neurons in a rat model of Parkinson's disease. We first investigated the ability of HAE cells to produce factors capable of promoting DA cell survival in vitro, and then tested whether HAE cell grafts survive and prevent the death of nigral DA neurons in rats with 6-hydroxydopamine lesions. A treatment with conditioned medium derived from HAE cell cultures enhanced the survival of tyrosine hydroxylase (TH)-immunopositive DA cells in serum-free cultures. The conditioned medium also protected the morphological integrity of TH-positive neurons against toxic insult with 6-hydroxydopamine. HAE cells were grafted into the midbrain of immunosuppressed rats. The rats were then subjected to a unilateral nigrostriatal lesion induced by intrastriatal infusions of 6-hydroxydopamine. HAE cell transplants were found to survive without evidence for overgrowth 2 weeks postgrafting. The number of nigral DA cells, detected with either TH-immunohistochemistry or retrograde labelling with fluorogold, was significantly increased in rats given the grafts as compared to that in control animals without the grafts. The results indicate that HAE cells produce diffusible molecules that can enhance the survival of DA neurons. Although the factors that contribute to the currently observed effects remain to be fully determined, implantation of HAE cells could be a viable strategy to counteract the loss of DA neurons in Parkinson's disease.

[Restoration of brain function by cell transplantation].

The first trial of restoring brain functions with cell grafting was performed in 1979 using a rat model of Parkinson's disease. Fetal nigral tissue was demonstrated to survive grafted tissue and to repair motor dysfunction in the model rat. The encouraging results indicate that cell transplantation may be useful to restore brain functions in neurodegenerative disorders in which a certain type of neuronal populations is specifically damaged. This review article discussed the possibility of cell transplantation therapy in several neurodegenerative disorders, such as Parkinson's disease, Huntington's disease and Alzheimer's disease.

Agraphia with abnormal writing stroke sequences due to cerebral infarction.

A 65-year-old, right-handed man presented with speech and gait disturbances. He was alert and cooperative, showing mild right hemiparesis and sensory disturbance. Spontaneous speech was fluent; object naming, word fluency and reading were fully preserved. Sentence repetition and verbal comprehension were mildly impaired. Writing was slow, hesitant and difficult for both spontaneous writing and dictation. Copying was better, although he had some difficulty in copying letters and also complex figures. Sequences of strokes in forming written characters were abnormal; strokes were formed by piecing together several fragments. Computed tomography and magnetic resonance imaging showed a subcortical infarct in the left frontoparietal region. Characteristics of agraphia resembled 'apractic agraphia' and agraphia may have resulted largely from loss or unavailability of the memory of motor patterns necessary for writing letters.