Modern Look at Transverse Myelitis and Inflammatory Myelopathy: Epidemiology of the National Veterans Health Administration Population.

BACKGROUND AND OBJECTIVES: To characterize population-level data associated with transverse myelitis (TM) within the US Veterans Health Administration (VHA). METHODS: This retrospective review used VHA electronic medical record from 1999 to 2015. We analyzed prevalence, disease characteristics, modified Rankin Scale (mRS) scores, and mortality data in patients with TM based on the 2002 Diagnostic Criteria. RESULTS: We identified 4,084 patients with an International Classification of Diseases (ICD) code consistent with TM and confirmed the diagnosis in 1,001 individuals (90.7% males, median age 64.2, 67.7% Caucasian, and 31.4% smokers). The point prevalence was 7.86 cases per 100,000 people. Less than half of the cohort underwent a lumbar puncture, whereas only 31.8% had a final, disease-associated TM diagnosis. The median mRS score at symptom onset was 3 (interquartile range 2-4), which remained unchanged at follow-up, although less than half (43.2%) of the patients received corticosteroids, IVIg, or plasma exchange. Approximately one-quarter of patients (24.3%) had longitudinal extensive TM, which was associated with poorer outcomes (p = 0.002). A total of 108 patients (10.8%) died during our review (94.4% males, median age 66.5%, and 70.4% Caucasian). Mortality was associated with a higher mRS score at follow-up (OR 1.94, 95% CI, 1.57-2.40) and tobacco use (OR 1.87, 95% CI, 1.17-2.99). DISCUSSION: This national TM review highlights the relatively high prevalence of TM in a modern cohort. It also underscores the importance of a precise and thorough workup in this disabling disorder to ensure diagnostic precision and ensure optimal management for patients with TM in the future.

Stiff person syndrome with Anti-GAD65 antibodies within the national veterans affairs health administration.

INTRODUCTION: Stiff person syndrome (SPS) is a neurological disorder characterized by muscle rigidity primarily in the truncal muscles, commonly associated with autoantibodies to the glutamic acid-decarboxylase 65 kD receptor (GAD65). There is limited epidemiological information on patients with SPS. METHODS: We performed a retrospective case review using the National United States Veterans Affairs Health Administration electronic medical record system. We analyzed prevalence, demographics, disease characteristics, and treatment outcomes in SPS patients who were anti-GAD65 antibody positive. RESULTS: Fifteen patients met our criteria. Point prevalence was 2.06 per million, and period prevalence was 2.71 per million. Men to women ratio was 14:1. All patients benefitted from treatment with symptomatic antispasmodic agents. Ten of 15 patients received intravenous immunoglobulin, with a majority demonstrating stable or improved modified Rankin scores. DISCUSSION: This investigation was a large North American epidemiological study of SPS with predominantly male patients. Symptomatic therapy was beneficial for most patients, with less clear sustained benefit of immunotherapy. Muscle Nerve 58:801-804, 2018.

Adult-onset Opsoclonus-Myoclonus Syndrome Associated With Ganglionic Acetylcholine Receptor Autoantibody.

INTRODUCTION: Opsoclonus-myoclonus syndrome (OMS) may have a toxin induced, parainfectious, or paraneoplastic etiology. Several autoantibodies have been associated with adult-onset OMS, most commonly antineuronal nuclear antibody 2 (Ri), and it is most frequently associated with breast or small cell lung cancer. The nicotinic ganglionic acetylcholine receptor autoantibody (α3-AChR Ab) has not been described in association. CASE REPORT: A 46-year-old woman was evaluated for symptoms of oscillopsia, tremor, gait imbalance, and mild cognitive deficits that began 6 weeks prior. Neurological examination demonstrated opsoclonus, myoclonus, and mild gait ataxia. Laboratory evaluation revealed an elevated α3-AChR Ab at 0.27 nmol/L (normal ≤0.02 nmol/L) with no other autoantibodies or infectious etiology detected. Thorough screening revealed no evidence of associated malignancy. Immunotherapy with weekly methylprednisolone led to significant improvement. CONCLUSIONS: This first reported case of α3-AChR Ab positivity in the setting of adult-onset OMS expands the spectrum of associated autoantibodies. The mechanism of disease may be linked to cholinergic nuclei within the brainstem. This case suggests including α3-AChR Ab in the evaluation of adult-onset OMS, and highlights the importance of further understanding α3-AChR within the brain.

Galanin expression in the mouse major pelvic ganglia during explant culture and following cavernous nerve transection.

Autonomic neurons commonly respond to injury/axotomy with an increased expression of neuropeptides including galanin and pituitary adenylyl cyclase-activating polypeptide (PACAP). The increased peptide expression may enhance neuronal survival and axonal regeneration. Using quantitative (Q) PCR and immunocytochemistry, the present study tested whether galanin expression increased in male mouse major pelvic ganglia (MPG) neurons in response to injury. Galanin transcript expression increased significantly in MPG neurons following 72 h in explant culture and 72 h after unilateral transection of the cavernous nerve. Under both conditions, the increase in galanin transcript levels was greater than the increase in PACAP transcript levels. In control MPG, galanin-IR nerve fibers formed pericellular arrangements around MPG neurons although few galanin-IR cells were evident and many of the galanin-IR cells may be small intensely fluorescent (SIF) cells. In 3-day-cultured MPGs, many more galanin-IR cells and nerve fibers were noted. The increased galanin expression was most apparent in neurons that were also immunoreactive for neuronal nitric oxide synthase, rather than tyrosine hydroxylase. Some explant-cultured MPG neurons exhibited immunoreactivity to galanin and PACAP. As reported previously for PACAP, there is an injury-induced increase in MPG galanin expression, which occurs preferentially in the parasympathetic postganglionic neurons.

PACAP expression in explant cultured mouse major pelvic ganglia.

The major pelvic ganglia (MPG) contain both parasympathetic and sympathetic postganglionic neurons and provide much of the autonomic innervation to urogenital organs and components of the lower bowel. Whereas many parasympathetic neurons were found to express vasoactive intestinal polypeptide (VIP), no MPG neurons exhibited immunoreactivity for pituitary adenylate cyclase-activating polypeptide (PACAP). However, in 3-day cultured MPGs, numerous PACAP-IR cells and nerve fibers were present, and transcript levels for PACAP increased significantly. In 3-day cultured MPGs, PACAP immunoreactivity was seen in cells that were also immunoreactive for VIP or neuronal nitric oxide synthase, but not tyrosine hydroxylase, indicating that PACAP expression occurred preferentially in MPG parasympathetic postganglionic neurons. Transcript levels for the VPAC2, but not VPAC1 or PAC1 receptor, also increased significantly following 3 days in culture. Transcript levels of activating transcription factor 3 (ATF-3), a marker of cellular injury, were increased 64-fold in 3-day explants, and ATF-3-IR nuclei were evident in both TH-IR and nNOS-IR neurons as well as in non-neuronal cells. In sum, these results demonstrate that, although only the parasympathetic neurons in explant cultured MPGs increase expression of PACAP, both sympathetic and parasympathetic postganglionic neurons in the cultured MPG whole-mount increase expression of ATF-3.