Raffi Topakian

Timing of stenting of symptomatic carotid stenosis is predictive of 30‐day outcome

For patients with symptomatic carotid stenosis, benefit from carotid artery stenting (CAS) highly depends on the 30‐day stroke and death rates. Identification of predictors of unfavourable outcome would help guide the patient selection. We analysed the influence of clinical and angiographic factors on the 30‐day outcomes of 77 consecutive patients who underwent CAS for ≥60% symptomatic carotid stenosis within 180 days of transient ischaemic attack or moderate stroke (modified Rankin Scale score ≤3). The 30‐day composite end‐point for stroke (7.8%) and death of any cause (1.3%) was 9.1%. Patients with complicated CAS were older than patients with uncomplicated CAS (mean age 75.1 ± 8.2 vs. 65.9 ± 9.5 years, P = 0.015) and underwent stenting significantly earlier after the qualifying event: median delay 1.5 weeks (range: 0.2–3.0) vs. 3.2 weeks (range: 0.5–26), P = 0.004. In multivariate logistic regression analyses, age [odds ratio (OR) = 1.148; 95% confidence interval (CI): 1.011–1.304 and P = 0.033] and delay of treatment <2 weeks (OR = 22.399; 95% CI: 2.245–223.445 and P = 0.008) remained the only variables significantly associated with 30‐day outcome. CAS carries a considerable risk in old patients and when performed early (<2 weeks) after the qualifying event. Future reports should address the timing of CAS.

High cardiovascular event rates in patients with asymptomatic carotid stenosis: the REACH registry

Background and purpose:  Data on current cardiovascular event rates in patients with asymptomatic carotid artery stenosis (ACAS) are sparse. We compared the 1‐year outcomes of patients with ACAS ≥70% versus patients without ACAS in an international, prospective cohort of outpatients with or at risk of atherothrombosis.

Thrombolysis Beyond the Guidelines Two Treatments in One Subject Within 90 Hours Based on a Modified Magnetic Resonance Imaging Brain Clock Concept

Background and Purpose— We report the first case of 2 intravenous thrombolysis treatments within 90 hours in a patient with early recurrent stroke. Summary of Review— A 50-year-old man had improved significantly after intravenous thrombolysis for acute stroke. On the fourth day, he deteriorated dramatically because of recurrent stroke. Evidence of vessel reocclusion and profound perfusion/diffusion mismatch constituted the rationale for a second thrombolysis treatment, which resulted in vessel recanalization and significant neurologic improvement. Conclusion— The pathophysiological information obtained by multimodal magnetic resonance imaging may suit as a brain clock when repeat thrombolysis treatment is considered for early recurrent stroke.

Late Outcomes After Carotid Artery Stenting Versus Carotid Endarterectomy. Insights From a Propensity-Matched Analysis of the Reduction of Atherothrombosis for Continued Health (REACH) Registry

Background— In patients with carotid artery disease, carotid endarterectomy (CEA) and carotid stenting (CAS) are treatment options. Controversy exists as to the relative efficacy of the 2 techniques in preventing late events. Methods and Results— The Reduction of Atherothrombosis for Continued Health (REACH) Registry recruited >68 000 outpatients ≥45 years of age with established atherothrombotic disease or ≥3 risk factors for atherothrombosis. Patients with CAS or CEA were chosen and followed up prospectively for the occurrence of cardiovascular events. Propensity score matching was performed to assemble a cohort of patients in whom all baseline covariates would be well balanced. Primary outcome was defined as death or stroke at the 2-year follow-up. Secondary outcome was stroke or transient ischemic attack. Tertiary outcome was a composite of death, myocardial infarction, or stroke and the individual outcomes. Of the 68 236 patients with atherothrombosis, 3412 patients (5%) had a history of carotid artery revascularization (70% asymptomatic carotid stenosis), 1025 (30%) with CAS and 2387 (70%) with CEA. Propensity score analyses matched 836 CAS patients with 836 CEA patients. At the end of 2 years of follow-up, in the propensity score–matched cohort, CAS was associated with a risk similar to CEA for the primary (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.57 to 1.26), secondary (HR, 1.20; 95% CI, 0.73 to 1.96), and tertiary (HR, 0.72; 95% CI, 0.51 to 1.01) composite outcome, death (HR, 0.63; 95% CI, 0.40 to 1.00), and stroke (HR, 1.48; 95% CI, 0.79 to 2.80). Conclusion— In a real-world cohort of patients with a history of carotid artery revascularization, CAS was comparable to CEA for late outcomes.

Postprocedural high-density lipoprotein cholesterol predicts carotid stent patency at 1 year

The durability of carotid artery stenting (CAS) is affected by the occurrence of myointimal proliferation and in‐stent restenosis (ISR). We aimed to identify clinical, angiographic, and laboratory predictors of ISR, paying special attention to postprocedural metabolic factors. A total of 102 consecutive patients with successful CAS for ≥70% atherosclerotic internal carotid artery stenosis were followed up with neurological assessment and duplex sonography 1 day, 1 month, and 1 year after CAS. Lipid profile and hemoglobin A1c were tested at the 1‐month follow‐up visit. Ten (10%) patients had ISR ≥50% after 1 year. Compared with patients without ISR (n = 92), patients with ISR were more often current smokers (33% vs. 70%, P = 0.034) and had significantly lower 1‐month high‐density lipoprotein (HDL) cholesterol: median (range) 47 (24–95) mg/dl vs. 39.5 (25–50) mg/dl, P = 0.031. Multivariate logistic regression analyses identified 1‐month HDL cholesterol >45 mg/dl as the only independent predictor of carotid stent patency at 1 year (P = 0.033, OR = 0.09, 95% CI 0.01–0.83). Postprocedural HDL cholesterol levels predict carotid stent patency at 1 year. With the possibility of elevation of HDL cholesterol by lifestyle changes and medication, this finding may have implications for the future management of patients undergoing CAS.

Thrombolytic therapy for acute stroke in Austria: data from the Safe Implementation of Thrombolysis in Stroke (SITS) register.

Background:  We aimed at determining the safety and efficacy of IV alteplase in Austrian versus non‐Austrian centres as documented in the Internet‐based registers Safe Implementation of Thrombolysis for Stroke – MOnitoring STudy (SITS‐MOST) and – International Stroke Thrombolysis Register (SITS‐ISTR).

Hypocalcemic choreoathetosis and tetany after bisphosphonate treatment

On the basis of several randomized controlled trials, zoledronic acid, a highly potent and long-acting bisphosphonate, is emerging as the new standard of care for managing skeletal morbidity in patients with advanced cancers involving bone.1 Symptomatic hypocalcemia after treatment with bisphosphonates has been described before.2,3 To our knowledge, this is the first report on a patient with hypocalcemic choreoathetosis after bisphophonate therapy. An 85-year-old man received an infusion of 4 mg zoledronic acid because of prostate cancer with extensive bone metastases. The day after the infusion, he developed perioral paresthesia and numbness and tingling in his extremities. He complained of new-onset debilitating fatigue and diffuse pain and stiffness in both legs. He was unable to stand or walk without the help of two people, while prior to bisphosphonate treatment he had been able to walk approximately 1,000 meters before claudication due to lumbar spine stenosis limited further walking. On admission, he appeared fidgety and gave the impression of general restlessness. He had increased tone, decreased distal sensation, and diminished reflexes in both legs. Plantar responses were flexor. Muscle power was normal, and there were no signs of disturbance of vigilance or mental function. His speech was slightly slurred. From time to time, he had selflimited painful tetanic spasms in both legs. The most striking neurological disturbances were brief paroxysms of unilateral or bilateral choreoathetoid arm movements. These episodes lasted up to a minute and occasionally appeared precipitated by movements such as reaching out. His past medical history was unremarkable for movement disorders and medication interfering with extrapyramidal motor systems or with psychotropic effects. Lesions in the basal ganglia and spinal cord compression were ruled out by magnetic resonance imaging. Laboratory tests revealed extreme hypocalcemia (0.7 mmol/L; normal: 2.15–2.6 mmol/L), while all other electrolytes were in the normal range. Calcium concentration corrected for albumin was identical to the measured calcium level. Creatine phosphokinase (CK) was highly elevated (2858 U/L; normal: 24–171 U/L), indicating rhabdomyolysis, while the myocardial-specific isoenzyme of CK was in the normal range ( 10% of CK). Parathyroid hormone (PTH) was significantly elevated (195 pg/mL; normal: 15–65 pg/mL). Electrocardiography (ECG) showed normofrequent sinus rhythm (70 bpm) with marked QT interval prolongation (496 ms). After initiation of treatment with calcium and vitamin D, the spells of choreoathetosis and tetany in his legs resolved within a few days and ECG showed normalization of QT time. Electrophysiological studies were compatible with mild to moderate distal symmetric axonal and demyelinating polyneuropathy. The patient declined further evaluation of the polyneuropathy because of lack of symptoms and was discharged from hospital with mild residual hypocalcemia after complete resolution of the presenting neurological symptoms. Neurological complications of hypocalcemia seem to be the consequence of loss of inhibition, primary neuronal hyperexcitability, or changes in permeability of muscle membranes. Clinically evident hypocalcemia, regardless of its cause, generally presents in milder forms and is usually the result of a chronic disease state.4 In patients with prostate cancer, increased calcium utilization by extensive osteoblastic metastases is hypothesized to be the primary phenomenon inducing hypocalcemia and compensatory hyperparathyroidism. In these patients, bisphosphonates may further reduce serum calcium and increase PTH levels, which could limit therapeutic effectiveness of bisphosphonates unless calcium supplementation were given in doses sufficient to maintain PTH in the normal range.5 We suppose that in our patient, preexisting asymptomatic chronic hypocalcemia worsened and was unmasked after bisphosphonate therapy. Rhabdomyolysis may have further reduced the level of metabolically active calcium by elevation of phosphates (from CK), lactate, and other anions that chelate calcium.4 Our case report illustrates that zoledronic acid may trigger severe symptomatic hypocalcemia with neuromuscular complications and new-onset movement disorders. To minimize adverse events, assessment and correction of calcium homeostasis before initiating zoledronate therapy are recommended.3

Cushing Syndrome due to Ectopic Adrenocorticotropin Secretion by Oncocytic Thyroid Nodule

A 60-yr-old woman presented with osteoporosis and atraumatic fractures of the spine and ribs in our neurological hospital in Linz, Upper Austria. She had a clinical history of bipolar affective disorder and cognitive decline, but the actual medical problem was lumbar pain. Treatment for osteoporosis already included bisphosphonates, vitamin D, and calcium. Endocrine evaluation for secondary osteoporosis revealed low TSH (0.17 U/ml) under prophylactic levothyroxine treatment (75 g/d) for multinodular goiter and ACTH-dependent hypercortisolism. Clinical evaluation presented obesity (weight, 75 kg, for 150 cm height), arterial hypertension, and diabetes mellitus. ACTH was elevated at 106 pg/ml, whereas morning serum cortisol (22 g/dl) was still in the normal range. Cortisol measured in 24-h urine was highly elevated at 502 g/d (normal range, 40–158 g/d). Dexamethasone suppression test with 1, 4, and 8 mg failed to suppress either plasma ACTH or cortisol in serum and/or 24-h urine (ACTH, 45 pg/ml; and cortisol, 20 g/dl and 400 g/d in all tests). Brain magnetic resonance imaging showed mild cortical atrophy and did not present any alterations of the pituitary. Because petrosal sinus catheterization cannot be practiced in the federal state of Upper Austria, it was postponed. Whole body fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) was done in May 2009 for tumor screening to detect a possible ectopic source of ACTH. A single nodule of the right thyroid lobe proved to be FDG avid (Fig. 1). Additionally, CT detected a lesion of the right kidney with a diameter of 2 cm that did not accumulate FDG. Because a former thyroid evaluation in March 2009— practiced in a regional institute in the “Salzkammergut” in Upper Austria—had evaluated this FDG-avid lesion as a cold nodule by Technetium-scintiscan and fine-needle-aspiration had shown oncocytic transformation of thyrocytes, we recommended thyroid surgery as the next step. Calcitonin screening had been negative in the patient. Near-total resection of the thyroid took place in June 2009, histology revealed regressive goiter, and a malignant lesion was not detected. The suspicious nodule was