Tonic pupil caused by adenoid cystic carcinoma versus postradiation changes to the ciliary ganglion.

A tonic pupil, without other features of an oculomotor neuropathy, is due to a lesion in the ciliary ganglion or short ciliary nerves. Here, we present a case of a tonic pupil in a woman with radiation-treated adenoid cystic carcinoma of the nasopharynx with perineural spread and skull base involvement. This a rare case of a tonic pupil caused by direct invasion of the ciliary ganglion or postradiation effects.

Spontaneous spinal epidural abscess in patients 50 years of age and older: a 15-year institutional perspective and review of the literature: clinical article.

OBJECT: A spinal epidural abscess (SEA) is a rare but severe infection requiring prompt recognition and management. The incidence of SEA has doubled in the past decade, owing to an aging population and to increased use of spinal instrumentation and vascular access. The optimal management of SEAs in patients 50 years of age and older remains a matter of considerable debate. In an older patient population with multiple comorbidities, whether intravenous antibiotics alone or in combination with surgery lead to superior outcomes remains unknown. The present study retrospectively analyzes cases of SEAs, in patients 50 years of age and older, treated at Duke University Medical Center over the past 15 years. METHODS: Eighty-two patients underwent treatment for a spinal epidural abscess between 1999 and 2013. There were 46 men and 36 women, whose overall mean age (± SD) was 65 ± 8.58 years (range 50-82 years). The mean duration of clinical follow-up was 41.38 ± 86.48 weeks. Thirty patients (37%) underwent surgery for removal of the abscess, whereas 52 (63%) were treated more conservatively, undergoing CT-guided aspiration or receiving antibiotics alone based on the results of blood cultures. The correlation between pretreatment variables and outcomes was evaluated in a multivariate regression analysis. RESULTS: Back pain and severe motor deficits were the most common presenting symptoms. Compared with baseline neurological status, the majority of patients (68%) reported being neurologically "better" or "unchanged." Twelve patients (15%) had a good outcome (7 [23%] treated operatively vs 5 [10%] treated nonoperatively, p = 0.03), while clinical status in 41 patients (50%) remained unchanged (10 [33%] treated operatively vs 31 [60%] treated nonoperatively, p = 0.01). Overall, 20 patients (25%) died (9 [30%] treated operatively vs 11 [21%] treated nonoperatively, p = 0.43). In a multivariate logistic regression model, an increasing baseline level of pain, the presence of paraplegia or quadriplegia on initial presentation, and a dorsally located SEA were independently associated with poor outcomes. CONCLUSIONS: The results of the study suggest that in patients 50 years of age and older, early surgical decompression combined with intravenous antimicrobial therapy was not associated with superior clinical outcomes when compared with intravenous antimicrobial therapy alone.

Evidence for astrocytes as a potential source of the glutamate excess in temporal lobe epilepsy.

Increased extracellular brain glutamate has been implicated in the pathophysiology of human refractory temporal lobe epilepsy (TLE), but the cause of the excessive glutamate is unknown. Prior studies by us and others have shown that the glutamate degrading enzyme glutamine synthetase (GS) is deficient in astrocytes in the epileptogenic hippocampal formation in a subset of patients with TLE. We have postulated that the loss of GS in TLE leads to increased glutamate in astrocytes with elevated concentrations of extracellular glutamate and recurrent seizures as the ultimate end-points. Here we test the hypothesis that the deficiency in GS leads to increased glutamate in astrocytes. Rats were chronically infused with methionine sulfoximine (MSO, n=4) into the hippocampal formation to induce GS deficiency and recurrent seizures. A separate group of rats was infused with 0.9% NaCl (saline) as a control (n=6). At least 10days after the start of infusion, once recurrent seizures were established in the MSO-treated rats, the concentration of glutamate was assessed in CA1 of the hippocampal formation by immunogold electron microscopy. The concentration of glutamate was 47% higher in astrocytes in the MSO-treated vs. saline-treated rats (p=0.02), and the ratio of glutamate in astrocytes relative to axon terminals was increased by 74% in the MSO-treated rats (p=0.003). These data support our hypothesis that a deficiency in GS leads to increased glutamate in astrocytes. We additionally propose that the GS-deficient astrocytes in the hippocampal formation in TLE lead to elevated extracellular brain glutamate either through decreased clearance of extracellular glutamate or excessive release of glutamate into the extracellular space from these cells, or a combination of the two.

Altered expression of brain monocarboxylate transporter 1 in models of temporal lobe epilepsy.

Monocarboxylate transporter 1 (MCT1) facilitates the transport of monocarboxylate fuels (lactate, pyruvate and ketone bodies) and acidic drugs, such as valproic acid, across cell membranes. We recently reported that MCT1 is deficient on microvessels in the epileptogenic hippocampal formation in patients with medication-refractory temporal lobe epilepsy (TLE). To further define the role of MCT1 in the pathophysiology of TLE, we used immunohistochemistry and stereological analysis to localize and quantify the transporter in the hippocampal formation in three novel and highly relevant rat models of TLE and in nonepileptic control animals. One model utilizes methionine sulfoximine to induce brain glutamine synthetase deficiency and recurrent limbic seizures, while two models employ an episode of perforant pathway stimulation to cause epilepsy. MCT1 was lost on microvessels and upregulated on astrocytes in the hippocampal formation in all models of TLE. Notably, the loss of MCT1 on microvessels was not due to a reduction in microvessel density. The similarities in MCT1 expression among human subjects with TLE and several animal models of the disease strongly suggest a critical role of this molecule in the pathogenesis of TLE. We hypothesize that the downregulation of MCT1 may promote seizures via impaired uptake of ketone bodies and antiepileptic drugs by the epileptogenic brain. We also propose that the overexpression of MCT1 on astrocytes may lead to increased uptake or release of monocarboxylates by these cells, with important implications for brain metabolism and excitability. These hypotheses can now be rigorously tested in several animal models that replicate key features of human TLE.