Distal symmetric polyneuropathy phenotype in patients with sensory neuronopathy at the time of electrodiagnosis.

INTRODUCTION/AIMS: It is unknown how often patients with sensory neuronopathy (SNN) present with a distal symmetric polyneuropathy (DSP) phenotype. In these cases, electrodiagnostic testing may discriminate SNN with a DSP phenotype from DSP. METHODS: We reviewed the records of patients who met SNN diagnostic criteria between January 2000 and February 2021 and identified patients with a DSP phenotype at the time of electrodiagnosis. RESULTS: Sixty-two patients fulfilled SNN diagnostic criteria. At symptom onset, 20 (32.2%) patients presented with distal symmetric sensory symptoms limited to the feet. However, most progressed rapidly over 6 months or developed asymmetric symptoms. At the time of electrodiagnosis, only seven (11.3%) patients had a DSP phenotype. Of these seven patients, four had cerebellar ataxia with neuropathy and vestibular areflexia syndrome, one had vitamin B6 deficiency, one was thought to be alcohol-induced, and one was idiopathic. DISCUSSION: Patients with SNN rarely present with a DSP phenotype at the time of electrodiagnosis. The finding that one third of cases resemble DSP at onset highlights the importance of clinical monitoring. In patients with a DSP phenotype, the presence of ataxia at onset or significant progression within 6 months may suggest the possibility of SNN and should prompt additional investigations, such as electrodiagnosis.

Comparison of the United Kingdom and United States approaches to approval of new neuromuscular therapies.

Many novel therapies are now available for rare neuromuscular conditions that were previously untreatable. Hereditary transthyretin amyloidosis and spinal muscular atrophy are two examples of diseases with new medications that have transformed our field. The United States and the United Kingdom have taken disparate approaches to the approval and coverage of medications, despite both providing incentives to develop therapies targeting rare diseases. The US requires less evidence for approval when compared with medications for common diseases and does not have a mechanism to ensure or even encourage cost-effectiveness. The Institute of Clinical and Economic Review provides in-depth cost-effectiveness analyses in the US, but does not have the authority to negotiate drug costs. In contrast, the UK has maintained a similar scientific threshold for approval of all therapies, while requiring negotiation with National Institute for Health and Care Excellence to ensure that medications are cost-effective for rare diseases. These differences have led to approval of medications for rare diseases in the US that have less evidence than required for common diseases. Importantly, these medications have not been approved in the UK. Even when medications meet traditional scientific thresholds, they uniformly arrive with high list prices in the US, whereas they are available at cost-effective prices in the UK. The main downsides to the UK approach are that cost-effective medications are often available months later than in the US, and some medications remain unavailable.

Patients who meet electrodiagnostic criteria for CIDP rarely present with a sensory predominant DSP phenotype.

INTRODUCTION: It is unknown how often patients with electrodiagnostic evidence of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a potentially treatable condition, present with a distal symmetric polyneuropathy (DSP) phenotype. METHODS: We reviewed the records of patients who presented to our electrodiagnostic laboratory between January 1, 2011, to December 31, 2019, and fulfilled electrodiagnostic criteria for CIDP to identify those who presented with a sensory predominant DSP phenotype. RESULTS: One hundred sixty-two patients had a chronic acquired demyelinating neuropathy, of whom 138 met criteria for typical or atypical CIDP. Nine of these patients presented with a sensory predominant DSP phenotype, among whom six were eventually diagnosed with distal acquired demyelinating symmetric (DADS) neuropathy; one with Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes (POEMS) syndrome; and two with idiopathic DSP. The prevalence of acquired chronic demyelinating neuropathies among all patients presenting with a DSP phenotype was estimated to be 0.34%. DISCUSSION: Patients who meet electrodiagnostic criteria for CIDP rarely present with a sensory predominant DSP phenotype, and electrodiagnostic testing rarely identifies treatable demyelinating neuropathies in patients who present with a DSP phenotype.

Multifocal motor neuropathy.

Multifocal motor neuropathy is an acquired disorder in which demyelination of motor axons, presumably due to autoimmune attack, results in progressive painless weakness without sensory loss. Motor axonal damage also occurs. It is a frequent mimic of motor neuron disease. Recognition of multifocal motor neuropathy is critical because it tends to be very responsive to treatment. Infusion of intravenous immunoglobulin is the initial treatment of choice, but other immunosuppressive treatments may also be effective. It appears that corticosteroids produce minimal benefit.

Cerebrospinal Fluid Protein Level and Mechanical Ventilation in Guillain-Barré Syndrome patients.

The prognostic value of cerebrospinal fluid (CSF) protein in Guillain Barré Syndrome (GBS) is unclear. We aimed to explore the potential association between CSF protein level and mechanical ventilation in GBS. We undertook a retrospective study of GBS patients from January 2000 to November 2019 at the University of Michigan. 94 patients were ultimately included for evaluation. After adjusting for the Erasmus GBS Respiratory Insufficiency Scale (EGRIS), we did not find a significant difference in CSF protein between ventilated and non-ventilated patients. Elevated CSF protein level does not appear to portend an increased likelihood of mechanical ventilation in GBS patients.

Minorities, men, and unmarried amyotrophic lateral sclerosis patients are more likely to die in an acute care facility.

Studies suggest that dying at home is a more favorable experience. This study investigated where amyotrophic lateral sclerosis (ALS) patients die and the patient demographics associated with dying in an acute care facility or nursing home compared to home or hospice. Centers for Disease Control and Prevention Multiple Cause Mortality Files from 2005 to 2010 were used to identify ALS patients and to classify place of death. Multinomial logistic regression was used to determine the association between patient demographics and place of death. Between 2005 and 2010, 40,911 patients died of ALS in the United States. Place of death was as follows: home or hospice facility 20,231 (50%), acute care facility (25%), and nursing home (20%). African Americans (adjusted multinomial odds ratio (aMOR) 2.56, CI 2.32-2.83), Hispanics (aMOR 1.44, CI 1.30-1.62), and Asians (aMOR 1.87, CI 1.57-2.22) were more likely to die in an acute care facility, whereas females (aMOR 0.76, CI 0.72-0.80) and married individuals were less likely. Hispanics (aMOR 0.68, CI 0.58-0.79) and married individuals were less likely to die in a nursing home. In conclusion, minorities, men, and unmarried individuals are more likely to die in an acute care facility. Further studies are needed to better understand place of death preferences.

Increased susceptibility to ventricular arrhythmias is associated with changes in Ca2+ regulatory proteins in paraplegic rats.

Paraplegia may increase susceptibility to ventricular arrhythmias by altering the autonomic control of the heart. Altered cardiac autonomic control has been documented to change the expression of genes that encode cardiac Ca2+ regulatory proteins. Therefore, we tested the hypothesis that paraplegia alters cardiac electrophysiology with concomitant changes in Ca2+ regulatory proteins in a manner that increases the susceptibility to ventricular arrhythmias. To test this hypothesis, intact (n = 10) and paraplegic (n = 6) male Wistar rats were chronically instrumented to measure atrioventricular (AV) interval, sinus cycle length, sinus node recovery time (SNRT), SNRT corrected for spontaneous sinus cycle (cSNRT), Wenckebach cycle length (WCL), and the electrical stimulation threshold to induce ventricular arrhythmias. In addition, relative protein abundance and mRNA expression for sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA), phospholamban, and the Na/Ca exchanger were determined in intact (n = 8) and paraplegic (n = 8) rats. Paraplegia significantly (P < 0.05) reduced AV interval (-25%), sinus cycle length (-24%), SNRT (-28%), cSNRT (-53%), WCL (-19%), and the electrical stimulation threshold to induce ventricular arrhythmia (-48%). Paraplegia significantly increased the relative protein abundances of SERCA (45%) and the Na/Ca exchanger (40%) and decreased phospholamban levels (-28%). In contrast, only the relative mRNA expression of the Na/Ca exchanger was increased (25%) in paraplegic rats. These data demonstrate that paraplegia enhances cardiac electrophysiological properties and alters Ca2+ regulatory proteins in a manner that increases susceptibility to ventricular arrhythmias.