Eugene Rossitch

Flow activates an endothelial potassium channel to release an endogenous nitrovasodilator.

Flow-mediated vasodilation is endothelium dependent. We hypothesized that flow activates a potassium channel on the endothelium, and that activation of this channel leads to the release of the endogenous nitrovasodilator, nitric oxide. To test this hypothesis, rabbit iliac arteries were perfused at varying flow rates, at a constant pressure of 60 mm Hg. Increments in flow induced proportional increases in vessel diameter, which were abolished by L,N-mono-methylarginine (the antagonist of nitric-oxide synthesis). Barium chloride, depolarizing solutions of potassium, verapamil, calcium-free medium, and antagonists of the KCa channel (charybdotoxin, iberiotoxin) also blocked flow-mediated vasodilation. Conversely, responses to other agonists of endothelium-dependent and independent vasodilation were unaffected by charybdotoxin or iberiotoxin. To confirm that flow activated a specific potassium channel to induce the release of nitric oxide, endothelial cells cultured on micro-carrier beads were added to a flow chamber containing a vascular ring without endothelium. Flow-stimulated endothelial cells released a diffusible vasodilator; the degree of vasorelaxation was dependent upon the flow rate. Relaxation was abrogated by barium, tetraethylammonium ion, or charybdotoxin, but was not affected by apamin, glybenclamide, tetrodotoxin, or ouabain. The data suggest that transmission of a hyperpolarizing current from endothelium to the vascular smooth muscle is not necessary for flow-mediated vasodilation. Flow activates a potassium channel (possibly the KCa channel) on the endothelial cell membrane that leads to the release of nitric oxide.

L-Arginine normalizes endothelial function in cerebral vessels from hypercholesterolemic rabbits

We hypothesized that normal vascular reactivity could be restored in vessels from hypercholesterolemic animals by exposing them to L-arginine, the precursor of endothelium-derived relaxing factor (EDRF). Basilar arteries were harvested from New Zealand white rabbits fed normal chow or that supplemented with 2% cholesterol for 10 wk. Vessels were cannulated for perfusion at physiologic pressure. Changes in vessel diameter were monitored by videomicroscopy. In comparison to normal vessels, those from hypercholesterolemic animals vasoconstricted more to KCl, endothelin (E), and 5-hydroxytryptamine (5-HT). Conversely, vasodilation to acetylcholine (ACh) (but not that to verapamil) was significantly impaired in the hypercholesterolemic animals. In vitro administration of L-arginine (3 mM) for 45 min normalized vasodilation to ACh and vasoconstriction to E, 5-HT, and KCl in the isolated vessels from hypercholesterolemic animals. This effect was stereospecific, since D-arginine had no effect. To conclude, these data confirm that hypercholesterolemia attenuates endothelium-derived relaxation, and enhances the sensitivity of these vessels to vasoconstrictors. In vitro administration of L-arginine normalized vascular reactivity of isolated vessels from hypercholesterolemic animals. Thus, hypercholesterolemia induces a reversible endothelial dysfunction that may be corrected by supplying the precursor of EDRF, L-arginine.

Ganglioglioma: a clinical study with long-term follow-up

Gangliogliomas are uncommon tumors of mixed neoplastic glial and neuronal elements. Because of their low incidence, few large series exist that fully describe the clinical characteristics of patients afflicted with this tumor. We have reviewed the medical records of 20 patients at Duke University Medical Center with histologically proven gangliogliomas. These patients typically presented within the first three decades of life and their most common presenting symptom was seizures. Therapies included surgical resection, either partial or total, radiation therapy, and/or chemotherapy. Long-term follow-up was achieved by chart review and by telephone interview. Patients who underwent gross total resection alone seemed to fare the best when comparing all treatment groups, and we therefore recommend this as the main form of treatment.

The Autonomic Dysfunction Syndrome: aetiology and treatment

Nine patients with autonomic dysfunction syndrome (ADS) characterised by sympathetic discharge and extensor posturing are presented. Morphine was given to three patients and in all cases consistently stopped the episodes. Dantrolene was given to one patient and reduced the severity of the extensor posturing without affecting the other components of the ADS. Bromocriptine was given to three patients and appeared to have both short- and long-term effects. Acutely, the drug partially corrected the hyperthermia and diaphoresis associated with these episodes. Two patients were given bromocriptine long-term. In one patient, the ADS was completely controlled and in the other, the frequency of the episodes decreased. The autonomic dysfunction syndrome appears to be related to both severe closed head injury and acute hydrocephalus. The clinical similarity of the two diverse etiologic groups and the absence of precipitating increased ICP in the former suggests the common theme is a release of the brain stem from higher control. The responses to morphine and bromocriptine suggest that the opiate and dopaminergic pathways play roles in the entity.

The development of lhermitte's sign during cisplatin chemotherapy: Possible drug-induced toxicity causing spinal cord demyelination

Cisplatin is a recognized neurotoxic agent that commonly causes ototoxicity and peripheral neuropathy. In conjunction with characteristic peripheral neuropathy, two patients treated with high‐dose cisplatin developed Lhermittes sign, a manifestation of posterior column spinal cord pathology. After cisplatin therapy was stopped, this symptom gradually resolved. This suggests that at high doses cisplatin may also cause demyelinating central nervous system lesions involving the spinal cord.

Metastatic melanoma to the spine. Demographics, risk factors, and prognosis in 114 patients.

Study Design. One-hundred-fourteen patients with metastatic melanoma of the spine were retrospectively reviewed. Objective. The goal was to define the demographics, risk factors, and prognosis for this population. Summary of Background Data. The incidence of melanoma is increasing faster than any other cancer. Therefore, orthopedic and neurologic surgeons will be increasingly confronted by patients with spinal metastases from melanoma. However, the demographics, risk factors, and prognosis remain unclear. Methods. From 7010 consecutive patients with melanoma, 114 were identified with clinically or radiographically evident spinal metastases. A comparison was made between these patients and the remainder of the population with melanoma seen at our institution using contingency table analysis with statistical significance determined by a chi-squared test. Survival data were represented by Kaplan-Meier curves, and log-rank testing was used for statistical comparisons. Results. Risk factors associated with the development of these metastases included primary lesions that were ulcerated, deeper than 0.76 mm, or of Clark level II, or located on the trunk or mucosel surfaces. The median survival time for all patients was 86 days, but this was reduced in patients with more than one metastatic site in addition to the spine. Conclusion. The prognosis for most patients with spinal metastases from melanoma is dismal. However, patients with metastatic disease limited to the spine and one other organ may survive for a relatively prolonged time and may be candidates for surgical intervention directed toward symptomatic relief.

Isolated central nervous system aspergillosis in the acquired immunodeficiency syndrome

Aspergillus infection involving the central nervous system are unusual, but should be included in the differential diagnosis in patients with the acquired immunodeficiency syndrome and neurologic signs and symptoms. Of the few reported AIDS cases with central nervous system aspergillosis, the majority have had focal brain abscesses. We report an atypical case that presented as a basal meningitis with pontine infarction secondary to invasive Aspergillus sinusitis.

Self-mutilation following brachial plexus injury sustained at birth

Self-mutilation after deafferentation injuries has been reported only rarely in adult humans. This behavior has been found to be similar to that observed in animals that have been subjected to experimental deafferentation. We present a child with a brachial plexus injury sustained at birth who began to bite her analgesic digits. Self-mutilation behavior in humans is reviewed and its relevance to current deafferentation pain animal models is examined. This behavior in humans further validates the current animal model of deafferentation pain.

Unilateral "akathisia" in a patient with AIDS and a toxoplasmosis subthalamic abscess.

The term “akathisia” was introduced by Haskovecl in 1903 and, translated from the Greek, means “not to sit.” The dieorder is characterized by motor restlessness and usually involvee pacing and the inability to sit still, with foot-tapping and other nervous gestures being prominent. Aknthisia is a well described extrapyramidal side effect of neuroleptic medication2 and ale0 occurs with Parkinson’s diseaee.3 The presentation her, always been bilateral. We report a patient with AIDS and a toxoplasmosis subthalamic abscess who developed unilateral akathisia. Case report. A.W. was a 54-year-old man with a history of IV drug abuse who was HIV positive, confirmed by ELISA titer and weetern blot. He first came to medical attention in 1987, when he presented with a right upper lobe infiltrate that resolved with a c o r n of broad spectrum antibiotics. Four months later, the patient was admitted to the hospital with complaints of jitterin-, reatleaaness, and intermittent frontal headaches that began 2 weeks before admimion. He was literally unable to sit or stand still and complained of feeling extremely anxious. Physical examination was significant for cachexia, old needle tract marks on the arms, generalized lymphadenopathy, and oral thrush. Neurologic examination revealed an anxious patient with dysrhythmic speech and no obvious language deficit. He was noted to be restleee, changing body position at least six t h e e per minute. Abnormal upper extremity movements included stroking the face and hair repeatedly with the right hand, and almost constant fidgety motions involving his right fingers, hand, and wrist. Abnormal movements were also present in the right lower extremity and included rapid tapping movements of the foot and sliding the foot back and forth on the floor. In addition, the patient would repeatedly cross and uncross his right leg over hie left. He was embarraeeed by these movementa and frequently eat on his right hand and acknowledged his lack of voluntary control of these movements. There was no limb weakness, sensory deficits, or choreiform movements of the mouth, tongue, or lips. He did have a mild right-sided hyperreflexia with a right Babinski sign. Gait was moderately wide based. He waked quickly with exaggerated swinging of the right arm, but without hemiballismus. CTs of the brain, with and without contrast, showed on the nonenhanced scan an area of hypodensity adjacent to the third ventricle on the left, locatedpredominantly in the lentiform nucleus, causing a left to right shift. The contrasted scan showed a nodular area of enhancement in the region of the left subthalamic nucleus with surrounding edema involving the lentiform nucleus (figure). In addition, there was a ring enhancing lesion in the left posterior parietal lobe, adjacent to the inner table of the skull, ale0 aeeociated with some edema. Thew finding were consistent with CNS toxoplmmosis, and the patient was started empirically on pyrethamine and sulfadiazine. Two weeks later, A.W. returned to the hospital because of naueea and vomiting. Laboratory data revealed a BUN of 58 and crentinine of 8.2. He continued to exhibit the unilateral akathisia and when given haloperidol for agitation, the movement dieorder became worse. The patient and family refused dialysis or further heroic measures. He continuedto have progressive renal deterioration and expired 1 month after onset of the neurologic illnees. A t autopsy, the brain was edematous, weighing 1,680 grama. On cut sections there was an area of necroeis (1.2 cm in diameter) involving the left subthalamic structures, with surrounding edema spreading throughout the left baeal ganglia and slight deviation of the third ventricle toward the right. A second, slightly larger area of necroeis (1.5 cm in diameter) was in the left parieto-occipital area. Microscopically, these areas revealed necrotizing Toxoplasma gondii encephalitis. Numerous intracellular cysts and extracellular trophozoites were present a t the margins of the necrotic foci, along with thrombosis and fibrinoid necrosis of vBBcular walls. Discussion. Neurologic eequelae of AIDS are relatively common. However, few extrapyramidal movement dieorders have been noted. Nath et a l 4 reported seven AIDS patients who had movement dieorders. Three had hemiballismus, two had segmental myoclonue, one had postural tremor with dyetonia, and one had paroxysmal dyetonia. Of relevance was a case with hemiballismus secondary to a toxoplmmoeis subthalamic abscess. Unlike our patient, however, this patient had a normal CT without edema or shift, the diagnosis was made at autopy and not radiographically. Although toxoplasmosis is the most common infection in AIDS patients with neurologic complications, movement disorders attributable to Toroplasma gondii were not reported until Nath et d4 The association of akathisia with postencephalitic Parkinson’s syndrome, idiopathic Parkinson’s dieeaee, and antipsychotic drug therapy suggeats that it ie an extrapyramidal movement dieorder. Although the pathogenesis is unknown, a current hypothesis implicates a competitive blockade of meeocortical poetsynaptic dopamine receptors? a notion not u n i v e d y accepted, however. Our case is of interest for several reasons. There is a paucity of documented movement dieorders secondary to AIDS, only one previous report of toxoplasmosis as the etiology,4 no previous report of akathisia in AIDS, and, finally, this is the first report of unilateral akathisia. Why our patient had akathisia and that of Nath et al4 had hemi-

Klüver-Bucy Syndrome in a Child with Bilateral Arachnoid Cysts: Report of a Case

Klüver-Bucy syndrome is an uncommon constellation of behavioral abnormalities resulting from bilateral temporal lobe damage. The syndrome is rare in adults and even less commonly seen in children. In this paper we present a child with Klüver-Bucy syndrome and bilateral temporal arachnoid cysts.