Chafic Karam

Polyneuropathy improvement following autologous stem cell transplantation for POEMS syndrome

Objective: To study the evolution of the neuropathy and long-term disability in a large cohort of patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome following autologous stem cell transplantation (ASCT). Methods: Retrospective chart review documenting the clinical, electrophysiologic, and laboratory characteristics of patients with POEMS syndrome undergoing ASCT at Mayo Clinic, Rochester. Results: Sixty patients with a median follow-up time of 61 months were studied. All patients had peripheral polyneuropathy and demonstrated neurologic improvement after ASCT (apart from one patient who died early). Before ASCT, 27 patients (45%) required a wheelchair and 17 (29%) required a walker or foot brace. At the end of the follow-up period, no patient was using a wheelchair and 23 patients (38%) were using a foot brace. The median Neuropathy Impairment Score improved from 66 to 48 points at 12 months and to 30 points at most recent follow-up (p < 0.0001). Median Rankin Scale score improved from 3 to 1.5 (p < 0.0001). Vascular endothelial growth factor levels decreased from a median of 452 to 63.5 pg/mL (p < 0.0001). The ulnar compound motor action potential amplitude (median) improved from 4.3 to 7.6 mV (p < 0.0001) and ulnar compound motor action potential conduction velocity (median) improved from 34 to 51 m/s (p < 0.0001). Predicted forced vital capacity improved from 81% to 88% (p < 0.0001). Periengraftment syndrome occurred in 24 patients. Fourteen patients required additional chemotherapy and/or radiation following ASCT, but there was no clinical deterioration in the neuropathy in any of these patients. Six patients died: 1 due to POEMS, 1 due to failed engraftment, and 4 due to other malignancies (2 myelodysplastic syndrome, 1 lymphoma, 1 metastatic lung cancer). Conclusion: Patients with POEMS syndrome who undergo ASCT have a significant and meaningful improvement of their neuropathy by multiple measurements during both short and long-term follow-up, which corresponds to reduction in morbidity and disability (none are in wheelchair long-term). Periengraftment syndrome was common but manageable. Fatal complications, although rare, did occur, usually in association with other malignancies. Classification of evidence: This study provides Class IV evidence that for patients with POEMS syndrome, ASCT improves neuropathy-related function.

Frontal lobe abnormalities on MRS correlate with poor letter fluency in ALS

Objective: To examine whether frontal lobe abnormalities on magnetic resonance spectroscopy (MRS) in amyotrophic lateral sclerosis (ALS) correlate with poor letter fluency (LF). Methods: Twenty-five patients with ALS (20 with definite, probable, or possible ALS and 5 with progressive muscular atrophy) performed an LF task, involving F word generation in 1 minute, and underwent MRS. Comparisons were made between patients with ALS with impaired LF and unimpaired LF based on an empirically derived cutoff score. A Spearman correlation was performed between the patients N-acetyl acetate/creatinine-phosphocreatinine ratio (NAA/Cr) and the number of F words generated. Results: LF was impaired in 50% of patients with ALS. Patients with impaired LF had reduced NAA/Cr in the DLPFC compared with those with unimpaired LF (p = 0.007). There was a significant correlation between LF and NAA/Cr in the DLPFC (r = 0.51, p = 0.0009). The ALS Functional Rating Scale score, clinical region of motor onset, and disease category had no effect on LF or NAA/Cr in the DLPFC. Conclusions: A reduced NAA/Cr in the DLPFC of patients with ALS is a marker of neuronal dysfunction and correlates with impaired performance on a clinical measure of executive function.

Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children

Editors’ Note: Commenting on the updated diagnostic criteria for pseudotumor cerebri syndrome (PTCS), De Simone et al. explain why the lumbar puncture (LP) opening pressure (OP) is not sufficient to make the diagnosis of PTCS. Commenting on the same criteria, Dasheiff explains how table 1 in the article may be misleading and should reflect more the association of those conditions cited with PTCS rather than causality. Friedman et al., authors of the criteria, respond. —Chafic Karam, MD, and Robert C. Griggs, MD

Complementary and Alternative Therapies in Amyotrophic Lateral Sclerosis

Given the severity of their illness and lack of effective disease-modifying agents, it is not surprising that most patients with amyotrophic lateral sclerosis (ALS) consider trying complementary and alternative therapies. Some of the most commonly considered alternative therapies include special diets, nutritional supplements, cannabis, acupuncture, chelation, and energy healing. This article reviews these in detail. The authors also describe 3 models by which physicians may frame discussions about alternative therapies: paternalism, autonomy, and shared decision making. Finally, the authors review a program called ALSUntangled, which uses shared decision making to review alternative therapies for ALS.

Eye of the storm.

This Gomori trichrome stain of a muscle biopsy was photographed with an iPhone camera placed over the microscope eyepiece. The typical necrotizing vasculitis bears a close resemblance to a hurricane viewed from space with the vessels lumen and wall representing the eye and eye wall of the storm, respectively.

Palliative Care Issues in Amyotrophic Lateral Sclerosis An Evidenced-Based Review

As palliative care physicians become increasingly involved in the care of patients with amyotrophic lateral sclerosis (ALS), they will be asked to provide guidance regarding the use of supplements, diet, exercise, and other common preventive medicine interventions. Moreover, palliative care physicians have a crucial role assisting patients with ALS in addressing health care decisions to maximize quality of life and cope with a rapidly disabling disease. It is therefore important for palliative care physicians to be familiar with commonly encountered palliative care issues in ALS. This article provides an evidenced-based review of palliative care options not usually addressed in national and international ALS guidelines.

Comprehensive rehabilitative care across the spectrum of amyotrophic lateral sclerosis

BACKGROUND Amyotrophic lateral sclerosis (ALS or Lou Gehrigs disease) is a neurodegenerative disease that results in progressive muscle weakness and wasting. There is no known cure and the disease is uniformly fatal. PURPOSE This review discusses current concepts in ALS care, from breaking the diagnosis to end-of-life care. People with ALS have several multidisciplinary needs due to a complex and dynamic disease process. They benefit from rehabilitation interventions that are individualized and have the goal of optimizing independence, function, and safety. These strategies also help minimize symptomatic burden and maximize quality of life. CONCLUSION Patient-centered, multidisciplinary care has a significant impact on the life of people with ALS and is the current standard of care for this patient population.

Vasculitic neuropathy following exposure to minocycline

Objective: To report 3 patients with minocycline-induced autoimmunity resulting in peripheral nerve vasculitis. Methods: We report 3 patients who, during minocycline treatment for acne vulgaris, developed subacute onset of pain and weakness caused by vasculitis in single and multiple mononeuropathy patterns. Results: Each patient underwent either a nerve or muscle biopsy that confirmed vasculitis. One patient additionally developed systemic symptoms (including fever, fatigue, and night sweats) and another had a posterior circulation stroke. Symptoms developed with either early or prolonged use of minocycline. Despite withdrawal of minocycline, patients needed long-term immunotherapy to gain neurologic improvement. Conclusions: Our findings suggest that the typical neuropathy associated with minocycline use is painful single or multiple mononeuropathy due to peripheral nerve vasculitis, which may also be accompanied by presumed CNS vasculitis (presenting as stroke).

Write click: Editor's choice

Editors’ Note: Wu et al. argue that, in certain races, the SMPD1 p.L302P mutation does not play an important role in Parkinson disease risk. Orr-Urtreger et al. are not surprised, since this is a founder Ashkenazi mutation. They suggest sequencing of the entire SMPD1 gene, in a much larger cohort of patients and controls, to examine the possible effects of rare SMPD1 mutations in non-Ashkenazi populations. Silvestri et al. and St. Louis et al. compare their findings in studies of sleep disorders in patients with myotonic dystrophy type 2 (DM2) and try to explain differences in their results, especially regarding obstructive sleep apnea. They agree on the necessity of prospective large-scale studies in patients with DM2 looking objectively at sleep abnormalities. —Chafic Karam, MD, and Robert C. Griggs, MD

Bright tongue sign in Pompe disease

A 38-year-old man was referred for progressive gait difficulty. A brain MRI was obtained as part of his workup prior to referral. Upon review of the brain MRI—reported normal by the radiologist—the tongue looked bright on the T1 sequence (figure). Investigation revealed that he had Pompe disease. Bright tongue sign is well-known in patients with bulbar amyotrophic lateral sclerosis but also can be seen in other neuropathies or myopathies that can affect the tongue muscle. Attention to abnormalities of the tongue, even on nondedicated brain MRI studies, may help neurologists with the diagnosis.1