Efficacy, Safety, and Tolerability of Switching from Oral Cholinesterase Inhibitors to Rivastigmine Transdermal Patch with 1-Step Titration in Patients with Mild to Moderate Alzheimer's Disease: A 24-Week, Open-Label, Multicenter Study in Japan.

BACKGROUND: Few studies have investigated treatment options for patients with Alzheimer's disease (AD) showing a poor response to oral cholinesterase inhibitors (ChEIs) in Japan. OBJECTIVE: To investigate the efficacy and safety of switching from oral ChEIs to rivastigmine transdermal patch in patients with AD. METHODS: In this multicenter, open-label, phase IV study in outpatient clinics in Japan, patients with mild-moderate AD who had a poor response to or experienced difficulty in continuing donepezil or galantamine were switched to rivastigmine transdermal patch (5 cm2; loaded dose 9 mg, delivery rate 4.6 mg/24 h) with a 1-step titration in week 4 (10 cm2; loaded dose 18 mg, delivery rate 9.5 mg/24 h), which was continued for 4 weeks in the titration period and 16 weeks in a maintenance period. The primary endpoint was the change in Mini-Mental State Examination (MMSE) total score from baseline to week 24. RESULTS: A total of 118 patients were enrolled and switched to rivastigmine, of which 102 completed the 24-week study. The MMSE total score was essentially unchanged during the study, with a least-square mean change (SD) of -0.35 (2.64) at week 24 (p = 0.1750). Exploratory analysis with a mixed-effect model comparing changes in MMSE between the pre- and post-switch periods suggested that switching to rivastigmine prevented a worsening of MMSE. Application site skin reactions/irritations occurred in 30.5% of patients overall, in 22.0% in the 8-week titration period, and in 10.2% in the 16-week maintenance period. CONCLUSION: Within-class switching from an oral ChEI to rivastigmine transdermal patch might be an efficacious and tolerable option for AD patients showing a poor or limited response to a prior oral ChEI.

[A case of dural arteriovenous fistula mimicking isolated transverse-sigmoid sinus successfully treated via the transvenous route].

A 66-year-old man was admitted to our hospital suffering from a left temporo-occipital intracerebral hematoma with bilateral thin subdural hematomas. Neurological examinations revealed slightly decreased cognitive function. Cerebral angiography demonstrated a left transverse-sigmoid dural arteriovenous fistula (TS-DAVF) with cortical venous reflux. The main feeders of the TS-DAVF consisted of multiple branches of the left occipital artery, and the left affected transverse-sigmoid sinus was occluded at both ends, i.e. the affected sinus was isolated. Transvenous embolization (TVE) was performed under general anesthesia. A contralateral approach failed to reach the affected sinus so that an ipsilateral approach was attempted. Contrast material was injected from the left jugular bulb and the route to the affected sinus was visualized. We succeeded in passing both a microguidewire and a microcatheter through the stenosed proximal sigmoid sinus to the fistula area of the affected sinus. The affected sinus was occluded with multiple platinum coils. Post-treatment angiography revealed disappearance of the cortical venous reflux and improvement of the cerebral perfusion. It is a challenging operation to approach an affected sinus through an occluded sinus. However, some cases of isolated TS-DAVFs have the possibility of being treated by TVE via the occluded sinus similarly to cavernous sinus DAVFs.

[Case of symptomatic epilepsy presenting with focal high intensity on diffusion-weighted image prior to initial convulsive seizure].

It has been reported that high intensity on diffusion-weighted image (DWI) in magnetic reasonance imaging (MRI) accompanying a reduction of the apparent diffusion coefficient (ADC) can be detected at the ictal or postictal stage of epileptic seizure. However, it remains unclear whether such a change results from persisting systemic convulsive seizure or from certain physiological changes such as recurrent epileptic discharge prior to the occurrence of obvious convulsion. We report here a case of symptomatic epilepsy displaying a high intensity area on DWI in MRI before convulsive seizure was initiated. A 64-year-old man was admitted to our hospital due to complaints of dizziness and motor weakness. CT and conventional MRI scans failed to reveal any new lesions except for the scar of a ventricular tube in the right parietal lobe, which had been removed due to shunt infection. The DWI, however, demonstrated an apparent high intensity in the right parietal cortex, and the ADC was significantly reduced as compared to that on the contralateral side. Five days after admission, the patient showed convulsive seizures beginning from the right face and upper extremity which subsequently developed to status epilepticus. Following recovery from the convulsions with administration of anticonvulsants, the high intensity of the right parietal lobe on DWI appeared to be diminished. The present case indicates that the manifestation of a high intensity on DWI concomitant with ADC reduction at the epileptic focus can be readily induced by the occurrence of epileptic discharges before convulsive seizure is evident.