Idiopathic neuropathy: new paradigms, new promise.

Idiopathic neuropathy, now designated as chronic idiopathic axonal polyneuropathy (CIAP), is a major public health problem in the United States. The disorder affects an estimated 5-8 million Americans, comprising about one-third of patients with neuropathy, based on data from referral centers. Typically, patients develop symptoms in the sixth decade or older. The onset is insidious, with numbness, paresthesias, and pain appearing over months to years. Although strength is generally preserved, the sensory loss and pain can be disabling. The clinical approach to this condition has evolved in important ways over the years, enabling improved diagnosis and characterization of this population. Current work has focused on identifying modifiable risk factors that may be associated with idiopathic neuropathy. The results may suggest that an underlying mechanism such as oxidative stress contributes to the development of CIAP.

Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures.

Induced pluripotent stem cells (iPSCs) outwardly appear to be indistinguishable from embryonic stem cells (ESCs). A study of gene expression profiles of mouse and human ESCs and iPSCs suggests that, while iPSCs are quite similar to their embryonic counterparts, a recurrent gene expression signature appears in iPSCs regardless of their origin or the method by which they were generated. Upon extended culture, hiPSCs adopt a gene expression profile more similar to hESCs; however, they still retain a gene expression signature unique from hESCs that extends to miRNA expression. Genome-wide data suggested that the iPSC signature gene expression differences are due to differential promoter binding by the reprogramming factors. High-resolution array profiling demonstrated that there is no common specific subkaryotypic alteration that is required for reprogramming and that reprogramming does not lead to genomic instability. Together, these data suggest that iPSCs should be considered a unique subtype of pluripotent cell.

Reversible nitrous oxide-induced myeloneuropathy with pernicious anemia: case report and literature review.

A previously healthy 27-year-old woman developed a subacute myeloneuropathy after receiving nitrous oxide anesthesia for dental procedures. Neurologic evaluation revealed that she was vitamin B(12) deficient due to underlying pernicious anemia. Discontinuation of nitrous oxide and supplementation with vitamin B(12) resulted in dramatic clinical improvement, with near-complete normalization of her neurologic examination. This case and published reports reviewed here emphasize that favorable outcomes are possible following prompt recognition and treatment of vitamin B(12) deficiency.

Primary lateral sclerosis.

The spectrum of motor neuron diseases ranges from disorders that clinically are limited to lower motor neurons to those that exclusively affect upper motor neurons. Primary lateral sclerosis (PLS) is the designation for the syndrome of progressive upper motor neuron dysfunction when no other etiology is identified. Distinction between PLS and the more common amyotrophic lateral sclerosis (ALS) relies primarily on recognition of their symptoms and signs, as well as on ancillary, although non-specific, laboratory data. In this review, we survey the history of PLS from the initial descriptions to the present. We discuss the role of laboratory, electrodiagnostic, and imaging studies in excluding other diagnoses; the findings from major case series of PLS patients; and proposed diagnostic criteria. Consistent differences are evident in patients classified as PLS compared to those with ALS, indicating that, despite its limitations, this clinical designation retains important utility.

Primary lateral sclerosis: clinical and laboratory features in 25 patients.

OBJECTIVE: : The objective of this study was to characterize the clinical features and natural history of primary lateral sclerosis (PLS). BACKGROUND: : PLS is a motor neuron disorder defined by corticospinal and corticobulbar tract dysfunction without clinically significant lower motor neuron involvement. METHODS: : We collected data from 25 patients with PLS seen in 2 academic neurology departments over a 5-year period. RESULTS: : The PLS population represented approximately 3% of acquired motor neuron disease cases seen during that period. Twenty-three patients (92%) presented with lower limb weakness, spasticity, or difficulty with ambulation. None presented with upper limb symptoms. Eleven patients (44%) developed bulbar symptoms. All patients had hyperreflexia and increased muscle tone. Muscle weakness was observed in 15 patients (60%) and tended to be mild and asymmetric. Needle electromyography (EMG) was normal or showed only fasciculations in 15 patients (60%); 10 patients had features of mild active denervation, consisting of fibrillation or positive sharp wave potentials, but the extent of these findings did not satisfy World Federation of Neurology electrophysiological criteria for the diagnosis of amyotrophic lateral sclerosis. Fourteen patients (52%) continued independent ambulation. Of the 10 patients with active denervation on EMG, 6 (60%) required a walker, scooter, or wheelchair at a mean follow up of 6.2 years. There were no fatalities over the 5-year period. CONCLUSIONS: : Our experience supports the observation that PLS progresses more slowly than other forms of acquired motor neuron disease, particularly amyotrophic lateral sclerosis. Follow-up data suggest that patients with active denervation changes develop greater disability.