Goshuyuto Reduced the Monthly Intake of Anti-headache Drugs and Improved Pain Status in Patients with 20-Year History of Medication Overuse Headache in an Outpatient Setting.

The management of medication overuse headache (MOH) is sometimes challenging, particularly for patients with a long disease duration. We observed that patients who used goshuyuto, a traditional Japanese medicine, exhibited a favorable clinical course. Two women who had a history of MOH for over 20 years were treated using 5.0-7.5 g/day goshuyuto in an outpatient setting. The treatment reduced their use of habitual drugs, including triptan (33-55%) and non-steroidal anti-inflammatory drugs (75-82%), as well as the headache impact test score-6 (16-23%) over 24 weeks. As goshuyuto has a protective effect on chronic headache and is reported not to lead to MOH, it is a good candidate for the treatment of patients with MOH in an outpatient setting, even for those with an over 20-year history of MOH.

Clinical significance of polyglutamylation in primary central nervous system lymphoma.

The therapeutic response to high-dose methotrexate (HD-MTX) therapy for primary central nervous system lymphoma (PCNSL) varies. Polyglutamylation is a reversible protein modification with a high occurrence rate in tumor cells. MTX incorporated into cells is polyglutamylated and strongly binds to dihydrofolate reductase without competitive inhibition by leucovorin (LV). Tumor cells with high polyglutamylation levels are selectively killed, whereas normal cells with lower polyglutamylation are rescued by LV. We hypothesized that the extent of polyglutamylation in tumor cells determines treatment resistance. Here, we investigated the therapeutic response of PCNSL to HD-MTX therapy with LV rescue based on polyglutamylation status. Among 113 consecutive PCNSL patients who underwent HD-MTX therapy in our department between 2001 and 2014, polyglutamylation was evaluated by immunostaining in 82 cases, with relationships between polyglutamylation and therapeutic response retrospectively examined. Human malignant lymphoma lines were used for in vitro experiments, and folpolyglutamate synthetase (FPGS), which induces polyglutamylation, was knocked down with short-hairpin RNA, and a stable cell line with a low rate of polyglutamylation was established. Cell viability after MTX treatment with LV rescue was evaluated using sodium butyrate (NaBu), a histone-deacetylase inhibitor that induces polyglutamylation by elevating FPGS expression. The complete response rate was significantly higher in the group with polyglutamylation than in the non-polyglutamylation group [58.1% (25/43) and 33.3% (13/39), respectively] (p < 0.05), and progression-free survival was also significantly increased in the group with polyglutamylation (p < 0.01). In vitro, the relief effect of LV after MTX administration was significantly enhanced after FPGS knockdown in al cell lines, whereas enhancement of FPGS expression by NaBu treatment significantly reduced this relief effect. These findings suggested that polyglutamylation could be a predictor of therapeutic response to HD-MTX therapy with LV rescue in PCNSL. Combination therapy with HD-MTX and polyglutamylation-inducing agents might represent a promising strategy for PCNSL treatment.

Thalamic stimulation alleviates levodopa-resistant rigidity in a patient with non-Parkinson's disease parkinsonian syndrome.

Deep brain stimulation (DBS) to the thalamic ventrointermediate nucleus (Vim) is a useful treatment in patients with tremor-dominant Parkinson's disease (PD). Efficacy to alleviate rigidity remains controversial. We report a 65-year-old right-handed man with persistent severe rigidity and bradykinesia on the right side despite daily administration of levodopa/carbidopa (600/60mg). His right-hand tremor was continuous at rest and present at action. His antiparkinsonian medications appeared ineffective and he reported difficulties with writing and eating. Repeated (123)I-meta-iodobenzylguanidine myocardial scintigraphy studies demonstrated a non-PD pattern. He underwent the stereotactic implantation of a DBS electrode into the left Vim. Using contacts 1 and 2 we started continuous unipolar stimulation with a pulse generator implanted in a subclavian pocket. This improved the tremor and the rigidity and bradykinesia of his right hand. Postoperative image analysis revealed the likelihood of simultaneous stimulation of the Vim and the nucleus ventralis oralis posterior. Our findings suggest thalamic stimulation as a therapeutic option for drug-resistant rigidity (and tremor) in patients with parkinsonian syndromes ineligible for DBS targeted at the globus pallidus internus or subthalamic nucleus.

Hemidystonia secondary to thalamic hemorrhage treated with GPi stimulation.

There have been few reports on the surgical treatment of secondary hemidystonias, most of which are due to basal ganglia stroke or trauma. We present 2 patients with hemidystonia secondary to thalamic hemorrhage whom we successfully treated with unilateral globus pallidus internus (GPi) stimulation. Case 1 is a 56-year-old man with abnormal posturing and intolerable muscle contraction pain in the left arm. Case 2 is a 73-year-old woman who developed severe abnormal posturing in the right arm and gait disturbance due to hyperextension of the right leg. The dystonic symptoms of both patients were refractory to medication. Three months after the inception of high frequency GPi stimulation, the motor scores on the Burke-Fahn-Marsden Dystonia Rating Scale were improved by 49.2% and 34.3% in Cases 1 and 2, respectively. We suggest GPi stimulation as a possible alternative to treat secondary hemidystonia.

Secondary cervical dystonia following stereotactic radiosurgery in a patient with thalamic glioma.

BACKGROUND: Cervical dystonia associated with structural lesion is uncommon. We report the first patient with secondary CD after stereotactic radiosurgery for thalamic glioma. Possible network abnormalities relevant to manifestation of CD were discussed. CASE DESCRIPTION: A 27-year-old woman complaining of headache and left motor weakness was found to have a thalamic tumor on the right side. The lesion was totally removed using transventricular approach. Histopathologically, tumor samples manifested features of anaplastic astrocytoma. She underwent stereotactic radiosurgery in addition to the conventional radiation and chemotherapy. Afterward, she returned to her usual life without any neurological deficits. Sixteen months postoperatively, the patient developed forced head tilting to the left side combined with chin lift. On the TWSTRS, she registered 15 for torticollis severity. The abnormal head posturing was alleviated by the sensory trick of touching her face with her right hand. Irregular-shaped lesion involving the thalamus, lenticular nuclei, midbrain, pons, and cerebellum was presented on magnetic resonance images. Steroid therapy effectively diminished the lesion size, and her abnormal head posturing was gradually ameliorated (TWSTRS severity scale = 3). CONCLUSION: The clinical-neuroradiological course of the present case strongly suggested that the lesion detected long after the surgery was due to radiation necrosis. The present study may provide a critical information in understanding pathophysiological mechanisms of CD that may involve substantial interactions between olivocerebellar and basal ganglia-thalamocortical circuits.

Treatment of cavernous sinus dural arteriovenous fistulae by external manual carotid compression.

OBJECTIVE: External manual carotid compression is a noninvasive method to treat cavernous sinus (CS) dural arteriovenous fistulae (DAVF). We studied a group of patients with CS-DAVF to identify what factors made complete resolution of their clinical symptoms and closure of the DAVF on magnetic resonance angiography (MRA) by compression therapy possible. METHODS: We treated 23 patients with CS-DAVF without cortical venous drainage or a recent decline in visual acuity by compression therapy. All were followed up by magnetic resonance angiography at 1, 3, 6, and 12 months after treatment and the characteristics of the imaging findings, their neurological symptoms, and the patterns of symptom improvement were examined. RESULTS: In Group A (n = 8), complete resolution was achieved by manual carotid compression. In the other 15 patients (Group B), complete resolution was not obtained. Group B manifested significantly higher ocular pressure and a significantly longer interval between symptom onset and compression treatment. In Group A, venous drainage was via the superior orbital vein with or without involvement of the inferior petrosal sinus. Closure of the CS-DAVF occurred within 4.1 months after the start of treatment. In three patients, symptom improvement progressed steadily and gradually. The other five patients with complete resolution experienced transient worsening of their symptoms at 2 to 4 months after the start of treatment and symptom resolution occurred within 4 to 7 months. CONCLUSION: We identified lower ocular pressure, a shorter interval between symptom onset and compression treatment, and venous drainage solely via the superior orbital vein without involvement of the inferior petrosal sinus as the factors in our CS-DAVF patients that made complete resolution by manual carotid compression possible.

Complete suppression of paroxysmal nonkinesigenic dyskinesia by globus pallidus internus pallidal stimulation.

Stereotactic functional surgery is being explored as potential therapies for medically intractable paroxysmal dyskinesias (PxD). We report on a 59-year-old man in whom stimulation of globus pallidus internus produced immediate and sustained relief of paroxysmal non-kinesigenic dyskinesia secondary to a rotator cuff tears on the left shoulder. Our finding strongly suggests that altered function of neuronal circuits of the basal ganglia underlies the manifestation of PxD.