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Action of phospholipases A2 and C on free fatty acid release during complete ischemia in rat neocortex

Effect of phospholipase C inhibitor and N-methyl-D-aspartate antagonist

Atsushi Umemura, Hideo Mabe, Hajime Nagai, and Fumihiko sugino

✓ The levels of brain free fatty acids rapidly increase after the onset of ischemia. The purpose of this study was to investigate the action of phospholipases A2 and C during complete ischemia based on the effects of a phospholipase C inhibitor (phenylmethylsulfonyl fluoride) and the N-methyl-D-aspartate antagonist MK-801 on the release of free fatty acids in rat neocortex. Complete brain ischemia was induced in rats with cardiac arrest by intracardiac injection of KC1. Free fatty acid levels in the neocortex were measured 0, 2, 4, and 8 minutes after cardiac arrest. Phenylmethylsulfonyl fluoride inhibited the release of free fatty acids primarily from phosphatidylinositol during the first 2 minutes of ischemia and from phosphatidylcholine and phosphatidylethanolamine at 4 to 8 minutes of ischemia. Conversely, MK-801 inhibited free fatty acid release mainly from phosphatidylcholine and phosphatidylethanolamine at 2 to 4 minutes of ischemia.

These results indicate that the release of free fatty acids during the first 2 minutes of ischemia can be attributed mostly to the action of phospholipase C, and that the activation of phospholipase C further influences the activation of phospholipase A2 in the subsequent course, while phospholipase A2 predominantly acts after 2 minutes of ischemia.

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Atsushi Umemura, Yuichi Oka, Kenji Okita, Noriyuki Matsukawa, and Kazuo Yamada

Object

Subthalamic nucleus deep brain stimulation (STN DBS) improves cardinal motor symptoms of Parkinson disease (PD) and reduces antiparkinsonian medication. Therefore, STN DBS seems to be well indicated for patients suffering from medication-induced psychotic symptoms. However, there are few available data dealing with the effect of STN DBS in this kind of patient. The authors studied the effect of STN DBS in patients with PD and severe medication-induced hallucinations or delusions.

Methods

The authors retrospectively reviewed the clinical course of 10 patients who suffered from severe medication-induced hallucinations or delusions and underwent bilateral STN DBS. Patients whose preoperative thought disorder score (Unified Parkinson's Disease Rating Scale Part I, item 2) was 3 or more were enrolled in this study. All patients underwent cognitive function examination and brain perfusion SPECT preoperatively to exclude dementia with Lewy bodies.

Results

Subthalamic nucleus DBS yielded significant improvement of motor function in all patients. In 8 patients, psychotic symptoms completely disappeared with significant reduction of dopaminergic medication. In 2 patients, hallucinations and delusions deteriorated immediately after surgery despite complete withdrawal of antiparkinsonian medication. However, these psychotic symptoms completely disappeared after a few months with administration of antipsychotics, and no recurrence was observed afterward in either patient.

Conclusions

Subthalamic nucleus DBS is a good treatment option for patients with PD who are suffering severe medication-induced hallucinations or delusion. However, vigilance is needed, because temporary deterioration of psychotic symptoms may occur after surgery.

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Atsushi Umemura, Yuichi Oka, Kenji Ohkita, Takemori Yamawaki, and Kazuo Yamada

Object

Parkinson disease (PD) is often accompanied by various postural abnormalities such as camptocormia (bent spine) or Pisa syndrome (lateral flexion). The authors studied the effect of subthalamic nucleus deep brain stimulation (STN DBS) on postural abnormality in patients with PD.

Methods

The authors retrospectively reviewed the clinical course of 18 patients who suffered from significant postural abnormality and underwent bilateral STN DBS. Patients whose preoperative posture score (Unified Parkinson's Disease Rating Scale III, item 28) was 2 or more in the “medication-on” state were enrolled in this study. Eight patients were considered to have camptocormia, and 10 patients were considered to have so-called Pisa syndrome. Nine patients showed apparent thoracolumbar spinal deformity on radiography. Most patients had significant motor fluctuations from levodopa.

Results

In 13 patients with moderate postural abnormality (score of 2 on item 28), 9 patients improved soon after surgery, but 1 patient relapsed. Two patients improved gradually over a long period after surgery, whereas 2 patients did not improve at all. In 5 patients with severe postural abnormality (score of 3 or 4 on item 28), 2 patients improved slightly in the long-term follow-up period after surgery, but 3 patients did not improve at all.

Conclusions

Postural abnormality in patients with PD could be ameliorated by STN DBS, and therefore surgery should be considered before irreversible spinal deformity develops.

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Atsushi Umemura, Jurg L. Jaggi, Carol A. Dolinskas, Matthew B. Stern, and Gordon H. Baltuch

✓ Generalized dystonia is one of the most disabling movement disorders. Ablative stereotactic surgery such as pallidotomy has been performed for medically refractory dystonia. Recently, deep brain stimulation (DBS) has appeared as an alternative to ablative procedures. Nevertheless, there have been few published reports detailing improvement in dystonia with DBS.

This 36-year-old man with Hallervorden—Spatz syndrome suffered from intractable primary generalized dystonia for 28 years. He was completely dependent for activities of daily living and wheelchair bound because of continuous severe dystonic movements in the face, tongue, neck, trunk, and upper and lower extremities while at rest. The Burke-Fahn-Marsden (BFM) Dystonia Rating Scale score was 112 (maximum 120 points). Bilateral DBS of the globus pallidus internus was performed and resulted in marked improvement in motor functioning and dystonic symptoms with a significant reduction in disability. The BFM score improved to 22.5 points (80% improvement) at 3 months postsurgery and the patient's dystonia was still well suppressed 1 year after surgery.

Bilateral pallidal stimulation is an effective and safe treatment for intractable generalized dystonia in Hallervorden—Spatz syndrome, even if the disability is severe and longstanding.

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Atsushi Umemura, Jurg L. Jaggi, Howard I. Hurtig, Andrew D. Siderowf, Amy Colcher, Matthew B. Stern, and Gordon H. Baltuch

Object. Deep brain stimulation (DBS) has been advocated as a more highly effective and less morbidity-producing alternative to ablative stereotactic surgery in the treatment of medically intractable movement disorders. Nevertheless, the exact incidence of morbidity and mortality associated with the procedure is not well known. In this study the authors reviewed the surgical morbidity and mortality rates in a large series of DBS operations.

Methods. The authors retrospectively analyzed surgical complications in their consecutive series of 179 DBS implantations in 109 patients performed by a single surgical team at one center between July 1998 and April 2002. The mean follow-up period was 20 months.

There were 16 serious adverse events related to surgery in 14 patients (12.8%). There were two perioperative deaths (1.8%), one caused by pulmonary embolism and the second due to aspiration pneumonia. The other adverse events were two pulmonary embolisms, two subcortical hemorrhages, two chronic subdural hematomas, one venous infarction, one seizure, four infections, one cerebrospinal fluid leak, and one skin erosion. The incidence of permanent sequelae was 4.6% (five of 109 patients). The incidence of device-related complications, such as infection or skin erosion, was also 4.6% (five of 109 patients).

Conclusions. There is a significant incidence of adverse events associated with the DBS procedure. Nevertheless, DBS is clinically effective in well-selected patients and should be seriously considered as a treatment option for patients with medically refractory movement disorders.

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Uzma Samadani, Atsushi Umemura, Jurg L. Jaggi, Amy Colcher, Eric L. Zager, and Gordon H. Baltuch

✓ Thalamic deep brain stimulation (DBS) has been demonstrated to be effective for the treatment of parkinsonian or essential tremor. To date, however, few data exist to support the application of this method to treat midbrain tremor.

A 24-year-old right-handed man underwent radiosurgery and subsequent resection of a recurrently hemorrhaging cavernous angioma located in the left side of the midbrain. The surgery exacerbated severe choreoathetotic resting and action tremors of his right extremities and trunk. The patient underwent placement of a deep brain stimulator into the left ventral intermediate nucleus of the thalamus (Vim). Postoperatively, decreased truncal ataxia and right-sided choreoathetotic tremor were demonstrated, with a 57% increase in dexterity as measured by task testing.

The authors demonstrate that DBS can be an effective treatment modality for disabling tremor after resection of a midbrain cavernous angioma.