The National ALS Registry: a recruitment tool for research.

INTRODUCTION: Subject recruitment is critical for understanding fatal diseases like ALS, however linking patients with researchers can be challenging. The U.S. population-based National ALS Registry allows recruitment of persons with ALS (PALS) for research opportunities. METHODS: The Registry's Research Notification Mechanism was used to recruit PALS aged ≥21 years; participants completed a Web-based epidemiologic survey. PALS (n = 2,232) were sent an email describing the study, and 268 surveys were completed. RESULTS: The mean age (± SD) of eligible participants was 57.7 ± 9.3 years for men and 61.5 ± 8.9 for women. Most were men (63%) and Caucasian (92%). Of 256 potentially eligible participants, 37.5% (n = 96) returned an authorization to disclose protected health information. ALS was confirmed for 94% (83/88) from physician responses. CONCLUSIONS: This analysis demonstrates the National ALS Registry's usefulness in recruiting PALS for research. This recruitment source can potentially foster the discovery of better treatment options and therapies, and of prevention strategies.

Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy.

INTRODUCTION: Disease inclusion in the newborn screening (NBS) panel should consider the opinions of those most affected by the outcome of screening. We assessed the level and factors that affect parent attitudes regarding NBS panel inclusion of Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and spinal muscular atrophy (SMA). METHODS: The attitudes toward NBS for DMD, BMD, and SMA were surveyed and compared for 2 categories of parents, those with children affected with DMD, BMD, or SMA and expectant parents unselected for known family medical history. RESULTS: The level of support for NBS for DMD, BMD, and SMA was 95.9% among parents of children with DMD, BMD, or SMA and 92.6% among expectant parents. CONCLUSIONS: There was strong support for NBS for DMD, BMD, and SMA in both groups of parents. Given advances in diagnostics and promising therapeutic approaches, discussion of inclusion in NBS should continue.

Facial diplegia, pharyngeal paralysis, and ophthalmoplegia after a timber rattlesnake envenomation.

The timber rattlesnake, also known as Crotalus horridus, is well known to cause significant injury from toxins stored within its venom. During envenomation, toxic systemic effects immediately begin to cause damage to many organ systems including cardiovascular, hematologic, musculoskeletal, respiratory, and neurologic. One defining characteristic of the timber rattlesnake is a specific neurotoxin called crotoxin, or the "canebrake toxin," which is a potent ß-neurotoxin affecting presynaptic nerves that can cause paralysis by inhibiting appropriate neuromuscular transmission. We present an unusual case of an 8-year-old boy bitten twice on his calf by a timber rattlesnake, who presented with a life-threatening envenomation and suffered multisystem organ failure as well as a prominent presynaptic neurotoxicity resulting in facial diplegia, pharyngeal paralysis, and ophthalmoplegia.

Accuracy and usefulness of ICD-10 death certificate coding for the identification of patients with ALS: results from the South Carolina ALS Surveillance Pilot Project.

The purpose if this study was to investigate the positive predictive value and sensitivity of the ICD-10 code G12.2, which is used to identify patients who have possibly died from ALS. All patients with a motor neuron disease diagnosis code during the study period (2001-2005) were identified using administrative data. South Carolina death certificate data were used to assess the positive predictive value and sensitivity of the ICD-10 code G12.2. Two hundred and seventy known cases of ALS linked to the death certificate data file. G12.2 was coded as either the underlying or contributing cause of death for 229 cases, sensitivity = 85%. There were 318 deaths due to ALS identified by the G12.2 code where a medical record was available for review. Of those, 205 contained information supporting the diagnosis of ALS, positive predictive value = 65%. This evaluation raises questions concerning the validity of using mortality data in forming epidemiological conclusions in this patient population. However, it does appear that mortality data can be used in the development of case-finding algorithms to identify ALS patients through the use of administrative data sets.

Validity of hospital discharge data for identifying cases of amyotrophic lateral sclerosis.

Inpatient hospital encounters and emergency department visits were examined to identify cases of amyotrophic lateral sclerosis (ALS).The ninth edition of the International Classification of Disease, clinical modification (ICD-9-CM) for ALS was confirmed for ALS was confirmed in 93% of inpatient discharges and in 91% of emergency department visits by the diagnostic standard (chart review). Yearly prevalence rates ranged from 2.94 to 3.28 per 100,000 residents. The low calculated prevalence rates suggest that this method of case identification is inadequate and must be combined with other data sets to maximize confirmation of the clinical diagnosis.

Voltage gated potassium channel antibodies in amyotrophic lateral sclerosis.

Although overlap exists between the clinical manifestations in patients with acquired peripheral nerve hyperexcitibility and amyotrophic lateral sclerosis (ALS), the presence of VGKC antibodies has not been associated with the development or clinical manifestations of motor neuron disease. We present the finding of elevated potassium channel antibodies in a cohort of patients with ALS and demonstrate a higher number of abnormal titer levels and higher mean titer levels in ALS patients compared to a cohort of patients with peripheral nervous system disorders. These results suggest the possibility of a subset of ALS patients where autoimmunity could play a role in disease development and progression.

Peripheral neuropathy in genetic mitochondrial diseases.

Peripheral neuropathy is an underrecognized but common occurrence in genetic mitochondrial disorders. To gain insight into the frequency and clinical presentation of this complication, nerve conduction studies were performed on 43 subjects with congenital lactic acidosis enrolled in a controlled clinical trial of oral dichloroacetate. Median and peroneal motor conduction studies and median and sural sensory conduction studies were performed on each patient. The mean amplitude of the peroneal motor nerve (P < 0.001) and the conduction velocities of the median (P < 0.001) and peroneal (P < 0.001) motor nerves were uniformly lower in our subjects than in healthy literature control subjects. There were no significant differences in sensory nerve conduction studies. A generalized reduction in motor nerve conduction velocity was the dominant electrophysiological abnormality in the patients in this study and was independent of age, sex, or congenital mitochondrial disorder. We postulate that cellular energy failure is the most likely common cause of peripheral neuropathy in patients with genetic mitochondrial diseases, owing to the high demand for adenosine triphosphate via aerobic carbohydrate metabolism by nerve tissue.

Juvenile-onset Leigh syndrome with an acute polyneuropathy at presentation.

Subacute necrotizing encephalomyelopathy or Leigh syndrome can be associated with a polyneuropathy. By far, the most commonly encountered neuropathy is a chronic neuropathy with features of demyelination, which can be the presenting manifestation of Leigh syndrome. On rare occasions, the neuropathy encountered can represent a more acute process. We describe a rare case of juvenile-onset Leigh syndrome presenting with an acute polyneuropathy.

Neurological deficits during treatment with tumor necrosis factor-alpha antagonists.

INTRODUCTION: Neurological deficits that occur during treatment with tumor necrosis factor (TNF)-α antagonists are rare, and their clinical features have not been fully elucidated. METHODS: Retrospective review of medical records of 9 patients who were given TNF-α antagonists, subsequently developed neurological deficits and were cared for at the Medical University of South Carolina between January 2002 and May 2010. Adverse drug reaction probability scale was used for the assessment of their causal connection. RESULTS: The underlying diseases for which TNF-α antagonists were administered included rheumatologic disorders (4), sarcoidosis (3), psoriasis (1) and Crohn's disease (1). Etanercept, infliximab or adalimumab was administered to these patients. Neurological complications included central or peripheral demyelination (5), antiphospholipid syndrome/central nervous system lupus (1), Epstein-Barr virus encephalitis (1), axonal sensory polyneuropathy (1) and small fiber polyneuropathy (1). TNF-α antagonists were discontinued in 8 patients and clinical improvement was seen in 3 of them. Additional therapies were given in 4 patients. An adverse drug reaction probability score suggested probable (3/9) and possible (6/9) causal relationships. CONCLUSIONS: Neurological deficits that develop during treatment with TNF-α antagonists are relatively rare but important potential complications of these drugs. Determining if the relationship between the neurological deficits and TNF-α antagonist therapy is causal can be challenging and can impact patient care.

Single-fiber electromyography during menstrual exacerbation and ovulatory suppression in MuSK antibody-positive myasthenia gravis.

We report a patient with muscle-specific tyrosine kinase (MuSK) antibody-positive myasthenia gravis who experienced worsening of myasthenic weakness associated with alterations in estrogen and progesterone levels during the administration of oral contraceptive therapy. Single-fiber electromyography was performed to document changes in neuromuscular transmission associated with the clinical exacerbation and subsequent resolution of the menstrual exacerbation and clinical improvement experienced with continuous monophasic oral contraceptive therapy. The potential long-term benefit of ovulatory suppression in MuSK antibody-positive myasthenia gravis is discussed.

Neurosarcoidosis.

Neurosarcoidosis is an uncommon disorder and requires a careful clinical evaluation to reach a diagnosis. Generally, patients with peripheral symptoms, which include paresthesias, muscle weakness, and stocking glove deficits, have a better outcome compared with those with central nervous system involvement. Patients with mass lesions or hydrocephalus tend to have more relapses and are often more resistant to routine therapy. Neurosarcoidosis often responds to glucocorticoids, usually within days or weeks of initiating therapy. Patients are usually maintained on 40 to 80 mg per day for 4 to 6 weeks, which is then tapered slowly. Alternative treatments for refractory neurosarcoidosis, or to reduce or eliminate steroids, include methotrexate, cyclophosphamide, azathioprine, cyclosporine, infliximab, chlorambucil, chloroquine, and hydroxychloroquine.