Gary L. Bernardini

Hemicraniectomy and Durotomy Upon Deterioration From Infarction-Related Swelling Trial: Randomized Pilot Clinical Trial

Background and Purpose— Hemicraniectomy and Durotomy Upon Deterioration From Infarction-Related Swelling Trial (HeADDFIRST) was a randomized pilot study to obtain information necessary to design a Phase III trial to evaluate the benefit of surgical decompression for brain swelling from large supratentorial cerebral hemispheric infarction. Methods— All patients with stroke were screened for eligibility (age 18–75 years, National Institutes of Health Stroke Scale ≥18 with Item 1a<2 [responsive to minor stimulation], and CT demonstrating unilateral, complete middle cerebral artery territory infarction by specific imaging criteria). All enrolled patients were treated using a standardized medical treatment protocol. Those with both ≥4 mm of pineal shift and deterioration in level of arousal or ≥7.5 mm of anteroseptal shift within 96 hours of stroke onset were randomized to continued medical treatment only or medical treatment plus surgery. Death at 21 days was the primary outcome measure. Results— Among 4909 screened patients, only 66 (1.3%) patients were eligible for HeADDFIRST. Forty patients were enrolled, and 26 patients developed the requisite brain swelling for randomization. All who failed to meet randomization criteria were alive at 21 days. Mortality at 21 and 180 days was 40% (4/10) in the medical treatment only and 21% (3/14) and 36% (5/14) in the medical treatment plus surgery arms, respectively. Conclusions— HeADDFIRST randomization criteria effectively distinguished low from high risk of death from large supratentorial cerebral hemispheric infarction. Lower mortality in the medical treatment only group than in other published trials suggests a possible benefit to standardizing medical management. These results can inform the interpretation of recently completed European trials concerning patient selection and medical management. Clinical Trial Registration— This trial was not registered because enrollment began before July 1, 2005.

Diagnosis and management of pathological laughter and crying.

Patients with various neurologic disorders exhibit exaggerated or inappropriate episodes of laughter, crying, or both without an apparent motivating stimulus or in response to stimuli that would not have elicited such an emotional response before the onset of the underlying disease. During these episodes, patients have difficulty controlling their emotional expression according to the contextual information. In contrast, patients with mood disorders have a pervasive and sustained change in their emotional experience and thus exhibit spells of laughter or crying because of an underlying mania or depression. This article focuses on the clinical presentation, diagnosis, prevalence, and proposed pathophysiological mechanisms of and available treatment options for this clinical phenomenon.

Importance of proper patient selection and endpoint selection in evaluation of new therapies in acute stroke: further analysis of the SENTIS trial.

Background The magnitude of treatment effect in acute stroke depends on several factors, including time from symptom onset (TFSO) to treatment and severity of the initial insult. Objective To report further evaluation of NeuroFlo therapy, focusing on the effect of time and stroke severity. Methods SENTIS was a prospective randomized trial (N=515) comparing standard medical therapy with/without NeuroFlo therapy. For this analysis, we evaluated outcomes in groups of patients based on TFSO and stroke severity: patients randomized <6 h, 6–10 h, and >10 h with mild (NIHSS<8), moderate (8–14), and severe (>14) symptoms at randomization. 90-Day mRS (modified Rankin Scale) scores and stroke-related death rates were compared between treatment groups. Results For patients randomized <6 h TFSO (n=128), the OR for mRS 0–2 was 3.11 (CI 1.30 to 7.46, p=0.011) for treated versus non-treated patients. In patients with disease of moderate severity (NIHSS 8–14, n=214), NeuroFlo-treated patients were more likely to have a good outcome (mRS 0–2; OR=1.84, CI 1.02 to 3.33, p=0.043). The stroke-related death rate was better in the treated group with TFSO >10 h and NIHSS >14 (n=42) (OR=7.10, CI 1.13 to 44.55, p=0.036). Conclusions The results of our analysis support the importance of careful selection of outcome measures and the impact that rapid treatment and initial stroke severity have on outcome. Clinical trial registration URL://http.clinicaltrials.gov.Unique identifier: NCT00119717.

Retrospective analysis of parenteral magnesium sulfate administration in decreased incidence of clinical and neuroradiological cerebral vasospasm: a single center experience

Abstract Objective: Experimental work suggests a neuroprotective role for magnesium sulfate in aneurysmal subarachnoid hemorrhage. We retrospectively review the incidence of clinically relevant vasospasm in patients treated or not with continuous magnesium infusion after onset of subarachnoid hemorrhage. Methods: All patient records in Albany Medical Center with the diagnosis of SAH between January 1999 and June 2004 were reviewed. Patients who presented to the emergency department within 72 hours of onset were entered in the study. Patients were defined as in clinical vasospasm if there was an acute neurological change in association with abnormal trancranial Doppler (TCD), CT angiogram (CTA) or digital subtraction angiography (DSA). Results: A total of 85 patients were selected. Magnesium sulfate was infused in 43 patients. When compared with patients who did not receive MgSO4, there was a statistically significant lower incidence of clinical and radiological vasospasm in those who had the continuous infusion of magnesium sulfate (p<0.01). There was no statistically significant difference between patients who were coiled or clipped. Conclusion: Continuous magnesium sulfate infusion for the management of clinically significant cerebral vasospasm is safe and reduces the incidence of clinically significant cerebral vasospasm. Large, multicenter, controlled studies should be performed in order to determine the true effectiveness of the treatment in a controlled setting.

Middle cerebral artery stenosis associated with moyamoya pattern collateralization.

Background and Purpose: Moyamoya disease is a well described phenomenon. This pattern of collateralization associated with isolated middle cerebral artery stenosis and the natural history of this entity have not been well described. Methods: Cerebral angiograms and CT angiograms performed between August 2004 and August of 2006 demonstrating moyamoya collateralization were retrospectively reviewed. All cases of middle cerebral artery stenosis associated with a rete pattern of collateralization were included in this series. Demographic, clinical, and angiographic data were obtained. Results: There were three cases of middle cerebral artery stenosis associated with a moyamoya pattern of collateralization. The average age of the patients was 36-years old, 2 were male, and all were Caucasian. All patients presented with ischemic symptoms. The average degree of stenosis was 91%. No stenosis was seen in the supraclinoid internal carotid arteries or elsewhere in the intracranial vasculature. Conclusion: We describe an unusual pattern of anastomosis associated with isolated severe middle cerebral artery stenosis or occlusion in Caucasians.

Efficacy of NeuroFlo device in treatment of patients with atrial fibrillation.

Atrial fibrillation (AF) is a well-established independent risk factor for stroke. We examined cerebral blood flow augmentation in the treatment of acute ischemic stroke (AIS) in patients with AF by performing secondary analysis of data from the Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS) trial, a randomized controlled trial evaluating NeuroFlo treatment in stroke patients within 14 hours of symptom onset. We report subgroup analyses of outcomes in SENTIS patients with a history or new diagnosis of AF. Among patients with AF, those treated with NeuroFlo demonstrated significant improvement over those not treated for multiple end points: global efficacy end point (P=.030), modified Rankin Scale (mRS) score 0-2 versus 3-6 (P=.029), and stroke-related mortality (P=.015). There was a significant improvement in global end point for those aged 60 years or older (P=.042) and 80 years or older (P=.017), with a trend toward improvement for age 70 years or older (P=.055), and significant improvement in those who achieved good outcomes (mRS score 0-2 versus 3-6) at age 60 years or older (P=.038), 70 years or older (P=.022), and 80 years or older (P=.008). NeuroFlo treatment in stroke patients with AF resulted in significantly better outcomes compared with nontreated patients with AF. Collateral flow recruitment, maintenance of cerebral blood flow around stroke core, and improvement of penumbral blood flow are potential mechanisms for these improved outcomes. NeuroFlo may represent a valid therapeutic option for patients with AF and AIS, and therefore, future trials of the device are warranted.

Presence of Decreased Intraepidermal Nerve Fiber Density Consistent with Small Fiber Neuropathy in Patients with Central Post-Stroke Pain.

OBJECTIVE: In our attempt to more completely assess potential underlying mechanisms responsible for central post-stroke pain (CPSP), we performed analysis of skin biopsies from the symptomatic lower extremity of four consecutive patients meeting inclusion criteria. BACKGROUND: Central post stroke pain (CPSP) is a chronic neuropathic pain syndrome with poorly understood pathophysiology. It manifests as severe treatment refractory pain in the affected limbs within weeks to months following a stroke. The diagnosis is made based on clinical criteria which are currently not well defined. DESIGN/METHODS: Patients were diagnosed with CPSP by a stroke-trained neurologist and pain management specialist; subjects whose persistent pain was clearly due to another pain syndrome were excluded. The specimens were obtained by means of 3 mm skin punch biopsy from the unilateral symptomatic lower extremity (thigh and calf). Immunohistochemistry analysis was performed to quantify the epidermal nerve fiber density (ENFD). RESULTS: The analysis of biopsies in all four patients meeting inclusion criteria revealed evidence of decreased ENFD within the symptomatic region. These findings have previously been considered diagnostic for small fiber neuropathy. CONCLUSIONS: We have demonstrated evidence of decreased ENFD in a small series of patients with CPSP. These findings do not imply causality; however, they do bring up several important questions for further consideration. Does the central nervous system injury associated with stroke result in small fiber neuropathy in certain patients? Are patients with asymptomatic, previously undiagnosed small fiber neuropathy at increased risk for developing CPSP following a stroke? Do these findings have any implication for treatment? Further studies including prospective analyses are necessary to better understand these findings for both diagnostic and treatment purposes. Study Supported by: Disclosure: Dr. Yushvayev-Cavalier has nothing to disclose. Dr. Amory has nothing to disclose. Dr. Bernardini has nothing to disclose. Dr. Argoff has received personal compensation for activities with Endo Pharmaceuticals, Eli Lilly, Janssen Pharmaceutica, Neurogesx, Horizon Pharma, Depomed, Eli Lilly, Covidien, Nuvo Research, Shionogi Pharmaceuticals, Pfizer, and Teva Neuroscience as a

Lateral Medullary Stroke in Patient with Granulomatous Polyangiitis

Granulomatous polyangiitis (GPA), also known as Wegener granulomatosis, is a systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis that infrequently affects the central nervous system. We report a 41-year-old man with lateral medullary infarction who developed rapidly progressive renal failure. He was diagnosed with GPA based on positive serum c-ANCA and antiproteinase 3 antibodies and demonstration of pauci-immune crescentic glomerulonephritis on kidney biopsy. He was treated with Coumadin, pulse steroids, cyclophosphamide, and plasmapheresis. He had resolution of his neurologic deficits and improvement in renal function. This case report highlights the importance to consider GPA vasculitis in the differential diagnosis of stroke in patients with development of acute kidney injury.

Cerebral autoregulation in acute SAH The more we know the better

Regulation of cerebral blood flow serves to protect the brain in the face of changing perfusion pressure. In acute subarachnoid hemorrhage (SAH), this autoregulation faces challenges both from reduced local cerebral perfusion pressure caused by cerebral vasospasm and from reductions in global cerebral perfusion pressure due to hydrocephalus. Early impairment of cerebral autoregulation plays a major role for development of delayed cerebral ischemia (DCI) in SAH patients.1 The mechanism of cerebral autoregulation itself involves myogenic and neurogenic (sympathetic or cholinergic) mechanisms. Impairment of these mechanisms in acute SAH may differentially contribute to early brain damage through DCI with territorial infarctions due to severe vasospasm, DCI with watershed infarctions due to microvascular dysfunction, or both. Understanding the pathophysiology of impaired vasoregulation in acute SAH and the potentially different roles in clinical complications would constitute an important step forward in development of specific treatments to improve autoregulation and outcomes in SAH.

Kevin Delgado Barron, MD (1929–2013)

Dr. Kevin Delgado Barron died on October 28, 2013, at his home in Loudonville, New York, in the company of his family. He was 84. Dr. Barron was born in St. Johns, Newfoundland, British Dominion, Canada, in 1929, third son of John A. Barron and Mercedes Delgado. He attended medical school at Dalhousie Medical School in Halifax, Nova Scotia, Canada. After concluding his internal medicine clerkship at Victoria General Hospital in Halifax and Queen Mary VA Hospital, Montreal, Canada, and a brief stint in 1952 as ships doctor on coastal steamer the SS Kyle, he completed his neurology residency at Montefiore Hospital, New York, followed by a fellowship in neuropathology. Subsequent academic appointments included instructor at the Neurological Institute at Columbia University Medical Center, New York; associate in neurology, psychiatry, and pathology at Northwestern University Medical School, Chicago; and section chief of neurology service and director of the electron microscope laboratory and the neuropathology research service at the VA Hospital, Hines, Illinois.