Michael J. Schneck

The Future of Neurology

Yogi Berra, the former New York Yankees baseball manager, known for his interesting phraseology, famously once said, “Its tough to make predictions, especially about the future.” While this has become somewhat of a tired cliche, there is an inherent validity to the argument that makes us somewhat cautious and humble in any discussion regarding the future of Neurology. At the risk of fumbling our way toward the truth, we remind ourselves that in order to find the truth, we need to ask the right questions. Other colleagues have written eloquently about the changing role of neurologists (Engstrom and Hauser, 1994; Bradley, 2000; Freeman and Vatz, 2010), and the fundamental changes facing Child Neurology (Ridel and Gilbert, 2010). A continuous stream of advances in basic neuroscience research, gene identification, neurogenomics, cutting-edge genetic techniques, neurodiagnostic tools including advanced neuroimaging technologies (Masdeu and Bakshi, 2005), and longitudinal biomarkers, coupled with new treatment modalities and paradigms for neurologic disease, suggests increased demands on available practitioners. In view of the growing aging population, associated with declines in infant mortality and treatment of infectious disease, more people will suffer from age related neurologic disorders such as stroke, dementia, Parkinsons disease, epilepsy, and autoimmune disorders (Engstrom and Hauser, 1994; Bradley, 2000; Freeman and Vatz, 2010; Weiner, 2007). In the past, a neurologist was recognized particularly for skilled diagnoses using clues derived from a thorough and elaborate history and physical examination, but treatment options were limited. Colloquially, the neurologist would “diagnose and adios.” With the advent of advanced neuroimaging and laboratory techniques, there has been much lament about the disappearance of the neurologists’ much vaunted skill in clinical diagnosis. And yet, the various tests, coupled with advanced treatment techniques, have certainly led to an explosion of opportunity, with both increased demand for neurologists and an increased number of people interested in the field. In the near future, the role of diagnostic testing in clinical neurology (as in all of medicine) will only further accelerate. There will be some value to the diagnostic prowess of neurologists in determining the appropriateness and meaning of complex and potentially unnecessary tests and procedures. As noted by Gooch and Amato (2010), in a discussion of the utility of anti-ganglioside antibodies in the diagnosis of multifocal motor neuropathy: “In this era of limited resources, the judicious exercise of sound clinical judgment in crafting a logical and efficient diagnostic evaluation has never been more important. Careful selection of the best path to the final diagnosis will not only most benefit our patients but will also as health reform continues to advance, insure that our precious (and finite) medical resources are not necessarily wasted” (Gooch and Amato, 2010). Still, academicians simply become Luddites if they lament how testing has superseded the neurologic history and physical examination which were never as accurate as we cared to admit. We respectfully suggest that the future of neurology will be critically dependent on harmonizing the tensions between clinical skills and an over-reliance on testing paradigms. The future of Neurology will also be reflected in the greater opportunities to develop therapeutic interventions, delay, or ideally prevent progressive neurodegenerative diseases, and the roles to be played by the new breed of neurologists in providing these interventions. There will likely be explosive growth in potential medical therapies including novel drugs, human pluripotent stem cell technology and gene therapies, and new immunosuppressant modalities in the near future (Mallarkey, 2008). There will also be an increased role for neurologists in interventional fields such as stroke, pain, neurostimulation, and even neuroregeneration. There will also be a continued separation between the practice of intensive and hospital-based neurology and office-based general and specialty neurology. The parallels with Cardiology/Internal Medicine combined with the growth of procedural non-surgical focused specialists in these fields are both obvious and inevitable given the profound shift toward a treatment oriented focus for neurology in the near future. The challenge for neurology will be whether we can satisfy the need for neurologic expertise in providing these treatments or whether others will pick up the slack for this pent-up demand for aggressive treatment of neurologic disease. The field of neurology remains one of the most dynamic areas of medicine, with advances on many fronts. Frontiers in Neurology offers an unprecedented opportunity for a more accessible, more manageable, and more useful dynamic interactive seminal exchange between the world community of neurologists and neuroscientists striving toward a common goal of excellence. Only by sharing your expertise and knowledge with the neurological community, can we achieve our ultimate goal of improving the quality of life and outcomes for patients with neurological disorders.

Venous thromboembolism: deep venous thrombosis and pulmonary embolism in a neurosurgical population

OBJECT Venous thromboembolism (VTE), a combination of deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major cause of morbidity and death in neurosurgical patients. This study evaluates 1) the risk of developing lower-extremity DVT following a neurosurgical procedure; 2) the timing of initiation of pharmacological DVT prophylaxis upon the occurrence of VTE; and 3) the relationship between DVT and PE as related to VTE prophylaxis in neurosurgical patients. METHODS The records of all neurosurgical patients between January 2006 and December 2008 (2638 total) were reviewed for clinical documentation of VTE. As part of a quality improvement initiative, a subgroup of 1638 patients was studied during the implementation of pharmacological prophylaxis. A high-risk group of 555 neurosurgical patients in the intensive care unit underwent surveillance venous lower-extremity duplex ultrasonography studies twice weekly. All patients throughout the review received mechanical DVT prophylaxis. Pharmacological DVT prophylaxis, consisting of 5000 U of subcutaneous heparin twice daily (initially started within 48 hours of a neurosurgical procedure and subsequently within 24 hours of a procedure) was implemented in combination with mechanical prophylaxis. The DVT and PE rates were calculated for each group. RESULTS In the surveillance group (555 patients), 84% of the DVTs occurred within 1 week and 92% within 2 weeks of a neurosurgical procedure. There was a linear correlation between the duration of surgery and DVT development. The use of subcutaneous heparin reduced the rate of DVT from 16% to 9% when medication was given at either 24 or 48 hours postoperatively, without any increase in hemorrhagic complications. In the overall group (2638 patients), there were 94 patients who exhibited clinical signs of a possible PE and therefore underwent spiral CT; 22 of these patients (0.8%) had radiological confirmation of PE. There was no correlation between the use of pharmacological prophylaxis at either time point and the occurrence of PE, despite a 43% reduction in the lower-extremity DVT rate with pharmacological intervention. CONCLUSIONS The majority of DVTs occurred within the first week after a neurosurgical procedure. There was a linear correlation between the duration of surgery and DVT occurrence. Use of early subcutaneous heparin (at either 24 or 48 hours) was associated with a 43% reduction of developing a lower-extremity DVT, without an increase in surgical site hemorrhage. There was no association of pharmacological prophylaxis with overall PE occurrence.

Intravitreal Ranibizumab and Bevacizumab: A Review of Risk

Ranibizumab (Lucentis®), a recombinant monoclonal antibody, blocks all active forms of vascular endothelial growth factor A and was the first treatment for age-related macular degeneration shown to improve visual acuity in a substantial percentage of patients rather than slowing visual loss. Bevacizumab (Avastin®) has a similar action, is related to the ranibizumab compound with respect to its structure, but has not been approved by the FDA for intravitreal use and therefore must be utilized only in an off-label setting. While ranibizumab was approved by the FDA at a dose of 0.5 mg per intravitreal injection, the manufacturer recently issued a letter to physicians warning of the increased risk of stroke at the FDA-approved dose as compared to a lower studied dose of 0.3 mg. An interim analysis of the ongoing SAILOR study revealed a 1.2% risk of stroke in the 0.5 mg arm versus 0.3% in the 0.3 mg arm (p = 0.02). It is unclear whether the trend toward a higher risk of stroke in patients receiving 0.5 mg dose of ranibizumab would persist in the final analysis, but details such as causality, topography, and severity of stroke in the SAILOR study should also be delineated. The risks of intraocular use of bevacizumab remain largely unknown at this time.

Summary of evidence-based guideline: Periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease Report of the Guideline Development Subcommittee of the American Academy of Neurology

Objective: To assess evidence regarding periprocedural management of antithrombotic drugs in patients with ischemic cerebrovascular disease. The complete guideline on which this summary is based is available as an online data supplement to this article. Methods: Systematic literature review with practice recommendations. Results and recommendations: Clinicians managing antithrombotic medications periprocedurally must weigh bleeding risks from drug continuation against thromboembolic risks from discontinuation. Stroke patients undergoing dental procedures should routinely continue aspirin (Level A). Stroke patients undergoing invasive ocular anesthesia, cataract surgery, dermatologic procedures, transrectal ultrasound–guided prostate biopsy, spinal/epidural procedures, and carpal tunnel surgery should probably continue aspirin (Level B). Some stroke patients undergoing vitreoretinal surgery, EMG, transbronchial lung biopsy, colonoscopic polypectomy, upper endoscopy and biopsy/sphincterotomy, and abdominal ultrasound–guided biopsies should possibly continue aspirin (Level C). Stroke patients requiring warfarin should routinely continue it when undergoing dental procedures (Level A) and probably continue it for dermatologic procedures (Level B). Some patients undergoing EMG, prostate procedures, inguinal herniorrhaphy, and endothermal ablation of the great saphenous vein should possibly continue warfarin (Level C). Whereas neurologists should counsel that warfarin probably does not increase clinically important bleeding with ocular anesthesia (Level B), other ophthalmologic studies lack the statistical precision to make recommendations (Level U). Neurologists should counsel that warfarin might increase bleeding with colonoscopic polypectomy (Level C). There is insufficient evidence to support or refute periprocedural heparin bridging therapy to reduce thromboembolic events in chronically anticoagulated patients (Level U). Neurologists should counsel that bridging therapy is probably associated with increased bleeding risks as compared with warfarin cessation (Level B). The risk difference as compared with continuing warfarin is unknown (Level U).

Acute Stroke Care in Illinois A Statewide Assessment of Diagnostic and Treatment Capabilities

Background and Purpose— To define areas for quality improvement in acute stroke care, a statewide assessment of preparedness for acute stroke diagnosis and treatment was carried out among 202 acute receiving hospitals in Illinois. Methods— Medical directors or their designees completed a 1-page survey form that addressed availability of personnel, diagnostic technology, and organized programs for the treatment of acute stroke patients at their facility. In the analysis, acute care receiving hospitals in the Greater Chicago Metropolitan Area (GCMA) (Cook, Dupage, Lake, Will, and Kane counties) were compared with those in the remainder of the state. Results— Of the acute care receiving hospitals, 91% responded to the survey. Overall, 99% had an emergency room receiving facility, 98.3% had a CT scanner, and slightly >70% had a recombinant tissue plasminogen activator (r-TPA) protocol. We found that 93.2% of residents in Illinois lived in a county with at least 1 acute care facility with an r-TPA treatment protocol. However, many of the non-GCMA receiving hospitals did not have a neurologist or a neurosurgeon available. Furthermore, specialized stroke diagnostic technology (eg, transcranial Doppler, diffusion-weighted MRI, MR angiography) was generally lacking in both the GCMA and non-GCMA, as were stroke community awareness programs and acute care stroke teams. Conclusions— Stroke is a preventable and treatable disease. However, there are barriers to stroke care that are based on the availability of personnel, diagnostic technology, and programs. A systematic approach to the organization, implementation, and maintenance of services could improve outcome for stroke patients and reduce the public health burden of this deadly disease.

Management of Arterial Blood Pressure in Acute Ischemic and Hemorrhagic Stroke

It is essential to control arterial blood pressure (BP) in both hemorrhagic and ischemic stroke patients to decrease morbidity following an acute event and decrease the long-term risk of stroke recurrence. Pathophysiology of BP control is dependent on understanding key relationships of cerebral blood flow and cerebral perfusion pressure. In the long term, hypertensive control decreases the rate of incident and recurrent hemorrhagic and ischemic stroke. In the acute setting, neither when to start antihypertensive medication nor the optimal BP target goals for short- and long-term control are well defined. There are several different drug classes available for BP control, with considerable debate as to which drugs are preferred for stroke patients. Medication selection and target BP depend on individual patient characteristics, including type of stroke, medical comorbidities, and timing of interventions in the context of the acute or postacute phases of stroke.

Bilateral occipital-parietal hemorrhagic infarctions following chiropractic cervical manipulation

A 26-year-old woman presented with acute headache and hand-motion vision in both eyes. One day prior to presentation she went to her chiropractor for cervical manipulation. The patient had received 20 chiropractic manipulations over the previous two years. CT scan and MRI showed bilateral, symmetric occipital-parietal hemorrhagic infarctions. Angiography revealed severe focal stenosis in the distal vertebral arteries bilaterally at the superior C1 level possibly representing dissections. There was also a pseudoaneurysm of the left vertebral artery at the C1 level. Risk factors included chiropractic manipulation, recent fever, and therapies for polycystic ovarian disease. The patient showed slow, steady improvement in her vision. Twenty days following admission, vision was 20/20 OU. The improvement in her vision most likely reflects the reduction in swelling and absorption of blood at the site of the strokes.

Is Psychological Stress a Risk Factor for Cerebrovascular Disease

Psychological stress has been implicated as a risk factor for a number of medical conditions. The association has been particularly well-studied for coronary heart disease. In contrast, there are only a few studies regarding the role of psychological stress as a risk factor for stroke. Additional research is clearly necessary to better delineate the degree of risk and the physiological mechanisms through which psychological stress may play a role in the development of cerebrovascular disease.

Correlation of Elevated Troponin and Echocardiography in Acute Ischemic Stroke

BACKGROUND Previous research has revealed a higher prevalence of elevated cardiac troponin T or I levels amongst patients admitted with stroke, which has been associated with increased cardiovascular events, higher mortality rates, and poor inpatient prognosis. Because cardiac comorbidities account for almost 20% of deaths after ischemic stroke, it is important to understand the relationship between troponin elevation, cardiac events, and acute ischemic stroke (AIS). METHODS We evaluated 137 consecutive patients ≥ 18 years of age who presented within 48 hours of AIS onset. All patients had laboratory markers drawn on admission, including troponin and brain natriuretic peptide, along with transthoracic echocardiogram with Doppler. The mean age of our study population was 71.7 ± 14.6 years. RESULTS Twenty-four of 137 patients (17.5%) had a positive troponin level. Sixteen of 24 (67%) patients with a positive troponin level had a new wall motion abnormality on echocardiogram that was suggestive of unstable atherosclerotic disease. On statistical analysis, we found a significant association between troponin and brain natriuretic peptide elevation with positive segmental wall motion abnormality on echocardiogram. CONCLUSIONS These study findings represent a new paradigm of interpreting elevated cardiac biomarkers and may help with risk stratification and diagnosis of patients presenting with AIS.

Management of Diffuse Low-Grade Cerebral Gliomas

World Health Organization grade II gliomas (GIIG) are diffuse, slow-growing, primary neuroectodermal tumors that occur in the central nervous system. They are generally seen in young individuals and are slightly more common in Whites and males. Most patients present with seizures but neurologic deficits are rare. Magnetic resonance imaging best detects GIIG and they are most frequently located in the frontal and temporal lobes. An accurate pathologic diagnosis is essential because the natural history of a GIIG may be unpredictable. In recent years, the emphasis has been on surgically removing as much tumor as safely possible to obtain an accurate diagnosis, improve symptoms, reduce tumor burden, and determine the need for adjuvant therapies. Radiation and chemotherapy are integral to the management of GIIG but their efficacy varies by tumor histology and is balanced against complications associated with them. Genetic, histopathologic, clinical, and radiographic changes are noted as GIIG progress to malignant gliomas. The risk of malignant transformation and subsequent survival may be predicted by pretreatment and treatment-related factors.