Nobuyoshi Kaito

Cytokine production in cerebrospinal fluid after subarachnoid haemorrhage

Pathophysiological mechanisms for vasospasm after subarachnoid haemorrhage (SAH) remain unclear and, so far, roles of cytokines in vasospasm have not been known. In the present study, we measured interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-alpha (TNF-alpha) concentrations in the cerebrospinal fluid (CSF) of patients with subarachnoid haemorrhage (SAH). ELISA assay were performed on 21 CSF samples from 7 patients with SAH and on 4 sera samples. Both IL-6 and IL-8 were detected in all CSF samples, but IL-1 alpha, IL-1 beta, and TNF-alpha were not detected. IL-6 and IL-8 were also detected in sera, but at much lower concentrations. This study indicates that IL-6 and IL-8 may play roles as immunomodulators in patients with SAH. In addition, it has been reported that IL-6 inhibits prostaglandin I2 production and increases the mRNA level of c-sis gene, suggesting that IL-6 may play an important role in vasospasm as vasoconstrictor.

Functional MRI-Based Therapeutic rTMS Strategy for Aphasic Stroke Patients: A Case Series Pilot Study

ABSTRACT Four poststroke patients with motor-dominant aphasia received 10 treatment sessions of low-frequency repetitive transcranial magnetic stimulation (rTMS). Each treatment session consisted of 1,200 pulses of stimulation and the site of stimulation was an area homologous to the most activated site on functional MRI performed prior to rTMS. Consequently, rTMS was applied to the right frontal lobe in two patients and to the left frontal lobe in two patients. Treatment resulted in improvement of language function in all four patients. Our therapeutic rTMS strategy seems to be a clinically feasible neurorehabilitative approach for poststroke aphasic patients.

Six-day course of repetitive transcranial magnetic stimulation plus occupational therapy for post-stroke patients with upper limb hemiparesis: A case series study

Purpose. To clarify the safety and feasibility of a 6-day protocol of low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with intensive occupational therapy (OT) for upper limb hemiparesis. Methods. In-hospital combination treatment was provided for 5 post-stroke patients with upper limb hemiparesis after more than 12 months of the onset of stroke. Over 6 consecutive days, each patient received 10 sessions of combination treatment with 1 Hz rTMS and intensive OT (one-on-one training and self-training). Motor function in the affected upper limb was evaluated by Fugl-Meyer Assessment (FMA), Wolf Motor Function Test (WMFT), Ten-Second Test at admission, discharge, and 4 weeks after treatment. Results. All patients completed the 6-day treatment protocol and none showed any adverse effects throughout the treatment. At the end of treatment, improvements in the scores of FMA, WMFT, and Ten-Second Test were found in all patients. No deterioration of improved upper limb function was observed at 4 weeks after the treatment. Conclusions. Our proposed protocol of combination treatment seems to be safe and feasible for post-stroke patients with upper limb hemiparesis, although the efficacy of the protocol needs to be confirmed in a large number of patients.

Neuroendoscopic placement of Ommaya reservoir into a cystic craniopharyngioma.

Abstract Introduction. Total removal of the tumor is the most acceptable therapeutic modality in the management of craniopharyngioma; however, there are innumerable factors that can upset treatment plans. Unresectable lesions are often treated with gamma knife surgery (GKS). Reduction of the cystic volume is necessary, to decrease the area to be treated with GKS. An Ommaya reservoir system is usually placed during open surgery or by stereotactic access. Materials and methods. The authors use a neuroendoscope for safer and less invasive placement of the Ommaya reservoir into deep-seated cystic lesions. The cystic component is aspirated, and the Ommaya reservoir tube is precisely guided and placed into the cyst cavity under neuroendoscopic control with a newly developed two-burr-hole technique. This neuroendoscopic procedure could make it easier to reduce cystic volume prior to GKS as the final procedure. This technique may also be used for instillation of chemotherapeutic agents and for repeat aspirations, making the achievement of cystic control more likely. This type of neuroendoscopic management is a safe and effective procedure and could be considered as an alternative management technique for some stubborn cystic craniopharyngiomas.

Low-frequency rTMS with language therapy over a 3-month period for sensory-dominant aphasia: Case series of two post-stroke Japanese patients

Purpose: To examine the safety and feasibility of therapeutic application of low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with language therapy for post-stroke patients with sensory-dominant aphasia. Subjects and methods: Two post-stroke Japanese patients with sensory-dominant aphasia were studied. In both patients, 10 sessions of 20-minute low-frequency rTMS with 1 Hz to the Wernickes area were provided throughout 6-day hospitalization, followed by weekly outpatient rTMS treatment for 3 months. The language therapy was also provided through the period of in- and out-patient treatment. Language function was evaluated using the Token test and the Standard Language Test of Aphasia (SLTA) at the start and end of the in-patient treatment and the end of the outpatient treatment. Results: The therapeutic protocol was well tolerated throughout the in- and out-patient treatments, without any adverse effects. The scores of the Token test and certain sub-categories of SLTA increased in both patients after the in-patient rTMS treatment. Persistent improvement of the score was noted over the 3-month post-discharge period. Conclusions: The proposed protocol of long-term application of low-frequency rTMS to the Wernickes area and language therapy is considered a safe and feasible therapeutic approach for post-stroke patients with sensory-dominant aphasia.

Investigation of Postmortem Functional Changes in Human Cerebral Arteries

This study demonstrated the time-dependent changes in postmortem responses of isolated human middle cerebral artery strips to vasodilators. The relaxation induced by prostaglandin (PG) I2 or nitroglycerin remained stable for 24 h postmortem. In arterial strips precontracted with PGF2α, substance P and bradykinin both elicited relaxation that was almost completely abolished by removal of the endothelium. The endothelium-dependent response to both peptides was significantly degraded in strips obtained >12 h postmortem. These results indicate a selective functional or anatomical vulnerability of the vascular endothelium compared with that of the vasodilator mechanisms of the smooth muscle in the postmortem period. However, cerebral arteries isolated from human cadavers within 12 h postmortem should be adequate for studies of both smooth muscle and endothelial reactivity to vasodilators.

A case of sphenoid sinus meningoencephalocele repaired by an image-guided endoscopic endonasal approach

We report a Japanese patient with a complaint of unilateral watery nasal discharge. Analysis of the nasal discharge showed it to contain high levels of sugar and transferrin, which indicated cerebrospinal fluid (CSF) rhinorrhea. A diagnosis of sphenoid sinus meningoencephalocele was easily made on the basis of the CT, MRI and nasal discharge findings. We performed surgery by an image-guided endoscopic endonasal approach (IGEEA). An image guidance system (IGS) was used to confirm the position of the bone defect and the prolapsed brain lobe. We resected the brain lobe, and used fat tissue and fascia to create an extracranial-intracranial blockade. As of 18 months after the operation, there is no evidence of infection or CSF leakage. The IGEEA enabled us to successfully repair the middle skull base using a multi-layer sealing technique, while the IGS allowed us to confirm the anatomical structures and successfully avoid causing collateral damage to the surrounding tissues. This case exemplifies the beneficial effect that of the development of surgical support equipment on the operative approach that is now indicated for sphenoid sinus meningoencephaloceles: the endonasal approach has largely replaced other approaches, such as lateral rhinotomy.

Suppression of cerebral vasodilation with endothelin-1.

We investigated the effect of endothelin-1 on relaxation responses induced by vasodilator substances in canine middle cerebral arteries to better understand regulation of cerebrovascular tone and its potential impact on mechanism of cerebral vasospasm. Endothelin-1 elicited concentration-dependent contractions in helical strips of canine cerebral arteries (EC50; 4.62 x 10(-9) M). Pretreatment with 10(-9) M endothelin-1 significantly reduced endothelium-dependent relaxation elicited by substance P and endothelium-independent relaxations by nitroglycerin, prostaglandin I2, and KCl. Although endothelin-1 in a lower concentration (10(-10) M) did not affect these endothelium-independent relaxations, it did inhibit endothelium-dependent relaxation caused by substance P. A low concentration (10(-10) M) of endothelin-1 also significantly reduced endothelium-dependent relaxation of canine mesenteric arteries induced by acetylcholine. Other vasoconstrictor peptides such as angiotensin-II and vasopressin did not inhibit endothelium-dependent and -independent relaxations. These results indicate that endothelin-1 not only produces cerebral vasoconstriction but also interferes with vasodilator mechanisms and that endothelium-dependent vasodilation is more sensitive to the inhibitory effect of endothelin-1 than endothelium-independent vasodiltion.

The potentiating effect of KC-404 on prostacyclin-induced vasodilation in isolated human cerebral artery

1. KC-404 (10(-9)-10(-6) g/ml) produced concentration-dependent relaxations in human middle cerebral arteries contracted with prostaglandin F2 alpha. 2. KC-404 (10(-8) and 10(-7) g/ml) has the ability to significantly potentiate prostaglandin I2-induced relaxations in human middle cerebral arteries. 3. KC-404, at least in low concentrations, may elicit human cerebral vasodilation predominantly by potentiating relaxant responses to prostaglandin I2 produced spontaneously in vascular wall. 4. KC-404 is expected to increase cerebral blood flow at least by dilation of major cerebral arteries, and this agent may be beneficial for the treatment of cerebrovascular disorders.

Re-organization of language function within the right hemisphere.

In March 1992, a 43-year-old righthanded woman (Edinburgh Inventory [1]) with no past illness was admitted to our hospital because of sudden-onset aphasia and right hemiplegia. Computed tomography showed a low-density area in the territory of the left middle cerebral artery (MCA). Magnetic resonance images (MRI) taken 2 months later confirmed the left hemisphere infarction within the blood supply area of the MCA (Fig. 1a and b). The Japanese Standard Language Test for Aphasia (SLTA) was used to evaluate language function. The SLTA consists of auditory verbal comprehension, speaking, reading comprehension, writing, and calculation. The overall response in SLTA is scaled from 0% (most severe) to 100% (normal). The patient could produce only aand showed severe failure on a sentence level with errors in auditory verbal comprehension and reading comprehension. Based on SLTA, the type of aphasia in this patient was considered global aphasia. Occupational, physical and speech therapies commenced 3 days after onset, provided 5 days/week, each session lasted 40 min. She showed gradual improvement and in November 1992, she was able to walk and was discharged from the hospital, although the right upper limbs showed disuse of synergic pattern. A repeat SLTA (3 days after onset to discharge) showed improvements with auditory verbal comprehension of 10– 80%, speaking of 0–70%, reading comprehension of 20–75% and writing of 0–50%, compared with normal values. She continued speech therapy once a week, but the result of SLTA did not improve after November 1992. In July 2004, at the age of 55 years (12 years since the first admission), she was admitted again to our hospital because of worsened right hemiplegia. Spasticity of the right upper and lower extremities was lower compared with neurological examination conducted during the first hospitalization. The leg showed flaccid paralysis. MRI taken 2 months later showed infarct lesions in the left hemisphere (Fig. 1c and d). Occupational, physical and speech therapies were provided from day 4 of hospitalization. Four months after the onset of the second episode, she walked using right ankle foot orthosis on the floor. She was later discharged from the hospital. The scores of auditory verbal comprehension, speaking and reading comprehension of SLTA at 1, 2 and 6 months after the second episode were almost identical to those recorded in November 1992, except for the writing ability, which was especially worse after the second episode (50% fi 5%). Functional imaging in adults during/ after recovery from aphasia due to lefthemisphere lesion reported increased hemodynamic activation of contralateral structures in association with verbal repetition [2] and comprehension tasks [3]. Furthermore, these reactions showed significant correlation with training-induced improvement of verbal comprehension [4]. These observations are further corroborated by the clinical data presented here. Most presumably, the loss of auditory/ reading comprehension and speaking after the first left-sided stroke was compensated for by the contralateral hemisphere because the subsequent ipsilateral infarction did not compromise these recovered language functions. The further decline of writing abilities, considered to be bound to the angular gyrus of the left hemisphere, can be explained by the larger extension of the second ischemic event in posterior direction. Both strokes, by and large, spared the rostral area of blood supply of the anterior cerebral artery. As these structures do not pertain to the perisylvian cortex, a significant contribution to language recovery is rather improbable.