Getting to value in neurological care: a roadmap for academic neurology.

Academic neurology is undergoing transformational changes. The public investment in biomedical research and clinical care is enormous and there is a growing perception that the return on this huge investment is insufficient. Hospitals, departments, and individual neurologists should expect more scrutiny as information about their quality of care and financial relationships with industry are increasingly reported to the public. There are unprecedented changes occurring in the financing and delivery of health care and research that will have profound impact on the mission and operation of academic departments of neurology. With the passage of the Patient Protection and Affordable Care Act (PPACA) there will be increasing emphasis on research that demonstrates value and includes the patient's perspective. Here we review neurological investigations of our clinical and research enterprises that focus on quality of care and comparative effectiveness, including cost-effectiveness. By highlighting progress made and the challenges that lie ahead, we hope to create a clinical, educational, and research roadmap for academic departments of neurology to thrive in today's increasingly regulated environment.

Outcomes research in amyotrophic lateral sclerosis: lessons learned from the amyotrophic lateral sclerosis clinical assessment, research, and education database.

OBJECTIVE: To examine the care of patients with ALS following the publication of the standardized recommendations for the management of patients with amyotrophic lateral sclerosis (ALS) published in 1999 by the American Academy of Neurology. METHODS: Specific aspects of ALS patient management have been evaluated serially using a national Amyotrophic Lateral Sclerosis Clinical Assessment, Research, and Education (ALS CARE) database to encourage compliance with these recommendations and to assure continuing quality improvement. RESULTS: The most recent analysis of 5,600 patients shows interesting epidemiological observations and treatment trends. Proper management of many ALS symptoms has increased substantially since the first publication of the guidelines, and awareness of pseudobulbar affect has increased. Other recommendations are underutilized: Only 9% undergo percutaneous endoscopic gastrostomy, although this procedure was recommended in 22% of patients; and noninvasive positive pressure ventilation was used by only 21% of patients despite being associated with improved 5-year survival rates. INTERPRETATION: This observational database has been a useful tool in monitoring compliance with the standard of care for patients with ALS and may have resulted in greater adherence to guidelines.

Using the Frontal Assessment Battery to identify executive function impairments in amyotrophic lateral sclerosis: A preliminary experience.

Up to 50% of persons with amyotrophic lateral sclerosis (ALS) develop cognitive impairments, particularly of executive function (EF). The Frontal Assessment Battery (FAB) provides a method for rapid assessment of EF. We investigated the FAB as an assessment of cognitive impairment among 16 subjects with ALS, and evaluated their performance on the FAB and the Mini-Mental State Examination (MMSE). Raw FAB and MMSE scores were Z-transformed using published age- and education-based norms. FAB Z-scores were significantly lower than MMSE Z-scores (p<0.03). Eight subjects (50%) were impaired (Z < or = -2) on the FAB while no subjects were impaired on the MMSE. MMSE and FAB scores did not vary as function of disease duration, laterality of onset, or Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Further study of the suitability of the FAB as a domain-specific screening measure of executive dysfunction for ALS is warranted.

Finding twinkle in the eyes of a 71-year-old lady: a case report and review of the genotypic and phenotypic spectrum of TWINKLE-related dominant disease.

Progressive external ophthalmoplegia (PEO) can be caused by a disorder characterized by multiple mitochondrial DNA (mtDNA) deletions due to mutations in the TWINKLE gene, encoding a mtDNA helicase. We describe a 71-year-old woman who had developed PEO at age 55 years. She had cataracts, diabetes, paresthesias, cognitive defects, memory problems, hearing loss, and sensory ataxia. She had muscle weakness with ragged red fibers on biopsy. MRI showed static white matter changes. A c.908G>A substitution (p.R303Q) in the TWINKLE gene was identified. Multiple mtDNA deletions were detected in muscle but not blood by a PCR-based method, but not by Southern blot analysis. MtDNA copy number was maintained in blood and muscle. A systematic literature search was used to identify the genotypic and phenotypic spectrum of dominant TWINKLE-related disease. Patients were adults with PEO and symptoms including myopathy, neuropathy, dysarthria or dysphagia, sensory ataxia, and parkinsonism. Diabetes, cataract, memory loss, hearing loss, and cardiac problems were infrequent. All reported mutations clustered between amino acids 303 and 508 with no mutations at the N-terminal half of the gene. The TWINKLE gene should be analyzed in adults with PEO even in the absence of mtDNA deletions in muscle on Southern blot analysis, and of a family history for PEO. The pathogenic mutations identified 5' beyond the linker region suggest a functional role for this part of the protein despite the absence of a primase function in humans. In our patient, the pathogenesis involved multiple mtDNA deletions without reduction in mtDNA copy number.

Projecting the Adequacy of the Multiple Sclerosis Neurologist Workforce.

BACKGROUND: Anecdotal reports suggest shortages among neurologists who provide multiple sclerosis (MS) patient care. However, little information is available regarding the current and future supply of and demand for this neurologist workforce. METHODS: We used information from neurologist and neurology resident surveys, professional organizations, and previously reported studies to develop a model assessing the projected supply and demand (ie, expected physician visits) of neurologists providing MS patient care. Model projections extended through 2035. RESULTS: The capacity for MS patient visits among the overall neurologist workforce is projected to increase by approximately 1% by 2025 and by 12% by 2035. However, the number of individuals with MS may increase at a greater rate, potentially resulting in decreased access to timely and high-quality care for this patient population. Shortages in the MS neurologist workforce may be particularly acute in small cities and rural areas. Based on model sensitivity analyses, potential strategies to substantially increase the capacity for MS physicians include increasing the number of patients with MS seen per neurologist, offering incentives to decrease neurologist retirement rates, and increasing the number of MS fellowship program positions. CONCLUSIONS: The neurologist workforce may be adequate for providing MS care currently, but shortages are projected over the next 2 decades. To help ensure access to needed care and support optimal outcomes among individuals with MS, policies and strategies to enhance the MS neurologist workforce must be explored now.

The natural history of cognitive dysfunction in late-onset GM2 gangliosidosis.

BACKGROUND: Late-onset GM2 gangliosidosis (LGG) is a rare disease that is often considered in the differential diagnosis of adolescents and young adults who present with multiple realms of neurologic dysfunction. Cognitive disturbances are common but have not been systematically studied. OBJECTIVE: To determine the natural history of cognitive dysfunction in patients with LGG. DESIGN: Case series and literature review. SETTING: Urban tertiary referral clinic. PATIENTS: Individuals with hexosaminidase A deficiency as the origin of LGG. MAIN OUTCOME MEASURES: Cognitive dysfunction, psychiatric symptoms, and cerebellar, upper motor neuron, lower motor neuron, or extrapyramidal symptoms and signs. RESULTS: Historical and examination data from 62 patients were found. Forty-four percent of LGG patients had some degree of cognitive dysfunction. Cognitive dysfunction was associated with a greater number of other elemental neurologic deficits. In 21 patients with acceptable longitudinal information, 8 (38%) had a static cognitive disorder, whereas progressive dementia was evident in 13 patients (62%), including 2 of our cases with serial neuropsychological testing. Neuroimaging often showed nonspecific cerebellar and/or cerebral atrophy. CONCLUSIONS: Cognitive dysfunction is a frequent manifestation of LGG. Patients who experience cognitive dysfunction are more likely to have a greater number of other neurologic manifestations of the disease. Cognitive dysfunction may take the form of static encephalopathy, but progressive dementia is more often encountered. The pathogenesis of cognitive dysfunction in this disease is unknown, highlighting the need for further study.

The practice of neurology: Looking ahead by looking back.

Over the last 50 years, there have been many improvements in therapy for individuals with neurologic disorders. Simultaneously, the complexity and cost of care have increased. The delivery of neurologic services is inefficient. The needs of both patients and neurologists are not being optimally addressed. Although greater attention is on the quality, safety, and value of the care, there remains a need for fundamental redesign in the way neurologic services are provided. The future practice of neurology will likely be interdisciplinary and provide both easy access and efficient coordination of services. No matter what changes in financing of health care are adopted, focus needs to be on reducing health care costs. Patients seeking neurologic care will expect seamless, innovative, and cost-effective services and to be active participants in their care. The proposed modifications address current demands and advocate for prospective innovative solutions. The changes proposed to improve care for patients will simultaneously make the careers of neurologists more gratifying and less stressful.

Anticholinesterase Therapy Worsening Head Drop and Limb Weakness Due to a Novel DOK7 Mutation.

Dok-7 myasthenia is an autosomal recessive congenital myasthenic syndrome due to DOK7 mutations. Anticholinesterase therapy is ineffective and may worsen the weakness in patients with Dok-7 myasthenia or few other forms of congenital myasthenic syndromes. We describe a 31-year-old man previously diagnosed with seronegative myasthenia gravis. Repetitive stimulation of the right spinal accessory nerve showed 51% decrement. Needle electromyography revealed myopathic changes in clinically affected muscles. Muscle biopsy was normal. The patient was referred to us for worsening weakness after taking pyridostigmine. We searched for DOK7 mutations and identified compound heterozygous mutations of a common c.1124_1127dupTGCC mutation and a novel splice site mutation, c.772+2_+4delinsCCGGGCAGGCGGGCA. Discontinuation of pyridostigmine improved weakness. He further regained strength with oral albuterol therapy and decrement was reduced to 25%. Worsening of symptoms with anticholinesterase therapy in patients with "seronegative myasthenia gravis" should prompt clinicians to consider a possibility of congenital myasthenic syndromes to avoid unnecessary use of immunosuppressive therapy. Patients with Dok-7 myasthenia respond well to oral albuterol treatment.

Oculopharyngeal muscular dystrophy as a cause of progression of weakness in antibody positive myasthenia gravis.

Many neuromuscular conditions cause bulbar and limb weakness, and when several conditions coexist they present additional diagnostic challenges. Here we describe a case of a 45-year-old woman with antibody positive myasthenia gravis since age 16, who then develops treatment-resistant weakness due to genetically proven oculopharyngeal muscular dystrophy. We conclude that the development of treatment-resistant weakness in myasthenia gravis should spur further work up for other neuromuscular disorders including oculopharyngeal muscular dystrophy.

Practicing medicine versus pushing paper.

A neurologist reflects on the realities of his workday after a patient asks why doctors complain about payers' bureaucratic oversight.