Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease caused by mutations in the TTR gene leading to multisystem organ dysfunction. Pathogenic TTR aggregation, misfolding, and fibrillization lead to deposition of amyloid in multiple body organs and frequently involve the peripheral nerve system and the heart. Common neurologic manifestations include: sensorimotor polyneuropathy (PN), autonomic neuropathy, small-fiber PN, and carpal tunnel syndrome. Many patients have significant progression due to diagnostic delays as hATTR PN is not considered within the differential diagnosis. Recently, two effective novel disease-modifying therapies, inotersen and patisiran, were approved by Health Canada for the treatment of hATTR PN. Early diagnosis is crucial for the timely introduction of these disease-modifying treatments that reduce impairments, improve quality of life, and extend survival. In this guideline, we aim to improve awareness and outcomes of hATTR PN by making recommendations directed to the diagnosis, monitoring, and treatment in Canada.

Background: High levels of uric acid (UA) are associated with various peripheral neuropathies. Furthermore, uric acid levels have been found to correlate with both the clinical and electrophysiological severity of diabetic sensorimotor polyneuropathy, mainly with sensory functions. Objectives: To determine whether higher UA levels are associated negatively with nerve function in healthy subjects. Methods: A total of 126 healthy subjects recruited prospectively for another study were included. We extracted demographic data, body mass index (BMI), blood pressure, Toronto Clinical Neuropathy Score (TCNS), electrophysiological findings, vibration perception thresholds (VPT), and laboratory test results including UA, hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), and lipid levels. Results: The mean age of the cohort was 56 ± 17 years with 56% females. Males had higher UA values compared with females. Univariate beta regression coefficient analysis between UA levels and demographic, clinical, electrophysiological, and laboratory findings showed significant positive correlations with male gender, components of the metabolic syndrome, and with VPT, while an inverse correlation was found with electrophysiological sensory parameters. A multivariate regression model showed positive correlations only with BMI, finger VPT, and triglycerides. Conclusion: Higher UA levels correlate with lower sensory nerve function in healthy subjects, expanding the evidence of possible negative influence of UA on peripheral nerves, although a causative role has not yet established.

To study the frequency of laboratory test abnormalities, and electrophysiological correlations, we performed a retrospective chart review of 226 patients with polyneuropathy. The frequency of laboratory test abnormalities, and correlations with electrophysiological findings were explored. Abnormal glucose handling tests were the most common findings (54%), followed by paraproteinemia (21%) and anemia (21%). The frequencies of paraproteinemia and anemia in our cohort were significantly higher than previously reported. In addition, several laboratory abnormalities correlated with electrophysiological findings of median neuropathy at the wrist, expanding current knowledge about the deleterious effects of various metabolic and hematologic derangements at this site.

Background: Preliminary studies have supported the utility of exercise as a treatment for Charcot–Marie–Tooth disease (CMT) patients. Despite being the most common inherited neuropathy, there remains a paucity of guidelines for CMT management. Methods: A retrospective chart review was performed on 297 CMT patients. Self-reported exercise and strength results from standardized dynamometer testing were obtained from adult patients’ first visits. Values were converted and analyzed based on previously reported age- and sex-matched normative values. Results: Participants with CMT2 had greater strength values than those with CMT1 in hand grip, elbow flexion, and dorsiflexion (p<0.05). Participants with CMT1 and CMT2 who exercised were statistically significantly stronger in elbow flexion and dorsiflexion than those who did not exercise. Conclusions: These preliminary results suggest that self-directed exercise is associated with greater strength in CMT patients of both CMT1 and CMT2 subtypes. Self-directed exercise may be a convenient, sustainable, and effective method of improving strength and decreasing disability in this population. Future research should explore the type of exercise prescription that best addresses the needs of the CMT population.

In 1892 Osler described ‘rapid loss of flesh’ in prolonged sepsis. Thereafter, for years, limb weakness was attributed to cachectic myopathy, and difficulty weaning from mechanical ventilation was attributed to diaphragmatic fatigue. In 1961 Mertens described ‘coma-polyneuropathies’, and in 1971 Henderson and colleagues described polyneuropathy in patients with burns. In 1984 Bolton and colleagues, in a series of reports, defined the clinical, electrophysiological and morphological features of septic encephalopathy and critical illness polyneuropathy. Evidence suggested that polyneuropathy was due to the ‘toxic’ effects of sepsis. Polyneuropathy was a common cause of difficulty in weaning when lung and cardiac cause had been excluded. Since 1984, cases of critical illness polyneuropathy have been reported from several countries. Moreover, a number of investigators reported instances of critical illness myopathy. Comprehensive studies by Latronico and colleagues indicated that polyneuropathy and myopathy often occurred together in the same patient. With successful treatment of sepsis, improvement often occurred in encephalopathy, polyneuropathy and myopathy, except in very severe cases.

Weakness of the limbs and respiratory muscles has increasingly been found to be a frequent event that complicates the medical history of patients in Intensive Care. The problem normally affects more serious cases and presents as muscular weakness leading to flaccid paralysis and difficulty in weaning patients off mechanical ventilation. This latter sign leads the intensivist to suspect possible involvement of the neuromuscular respiratory system. Unfortunately, in-depth clinical assessment of the neuromuscular respiratory system is difficult with critically ill patients, and electrophysiological studies have been used instead to overcome this problem. Of these latter, electric and electromagnetic stimulation of the phrenic nerve have been successful (along with needle electromyography of the diaphragm) in identifying the causes of neuromuscular respiratory insufficiency, especially in Intensive Care. In this brief chapter, we will be discussing the technique of electric stimulation of the phrenic nerve and neuromuscular respiratory insufficiency within the field of critical illness polyneuropathy.

With better survival of critically ill patients, ‘de novo’ arising neuromuscular complications like critical illness myopathy or polyneuropathy have been increasingly observed. Prolonged hospitalization not only imposes risks like pneumonia or thrombosis on patients but also represents a real budget threat to modern intensive-care medicine. Clinical symptoms like muscle weakness and weaning failure are common to critical illness myopathy and critical illness polyneuropathy and do not allow for distinction. Specific therapies are not yet available, and the quest for the pathomechanisms has proved more complicated than anticipated. Especially for critical illness myopathy, multiple sites of disturbances to the excitation–contraction coupling cascade are possible causes of muscle weakness. The present review summarizes the epidemiological, clinical and diagnostic features of critical illness myopathy and then focuses on current concepts of the presumed pathomechanisms of critical illness myopathy. Sepsis was shown to be a major cause of critical illness myopathy and special emphasis will be placed on how sepsis and inflammatory mediators influence (i) the membrane excitability at the level of voltage-gated ion channels and (ii) the intracellular protein signalling that results in selective loss of myosin protein content and muscle wasting. For (i), critical illness myopathy represents a new type of acquired channelopathy affecting the inactivation properties of Na+ channels. For (ii), both protein proteolysis and protein build up at the transcriptional level seem to be involved. Findings from different studies are put into a common context to propose a model for cytokine-mediated failure of muscle in severe sepsis. This can open a series of new possible trials to test specific therapeutic strategies in the future.

Neuromuscular complications encountered in intensive care can be due to peripheral nerves (polyneuropathies), muscles (myopathies), neuromuscular end-plate (transmission deficit) or a combination of these. Neurophysiopathological tests that enable us to diagnose and maybe differentiate between these causes are essentially electroneurographs and electromyographs. These assess, either directly or indirectly, the integrity of the peripheral system, both sensory (centripetal afferent pathways) and motor (lower motor neurones, neuromuscular junction, muscle membrane and contractile substrate). Electrical activity in the muscle is measured using a special device (an electromyograph) comprising preamplifiers, a computer with special programmes and algorithms for analysing, digitalizing, amplifying and filtering the recorded signal and a monitor on which to visualize the on-line trace. The machine also has speakers. These serve to recognize and identify the physiological events being recorded as they make such unusual, individual sounds. An electric stimulator with constant current can be used to stimulate branches of superficial nerves (motor, sensory or mixed) so that electric conduction speed can be studied and the sensory or motor response analysed. The results can be saved on a hard disc or on any magnetic or digital support, viewed off-line or even printed.

Direct muscular stimulation is quick, simple, non-invasive and can be carried out at the patient’s bedside. More importantly, it is reliable even when the patients cannot cooperate or are comatose. From the small amount of data available, it seems to be as accurate as neuromuscular biopsy in diagnosing critical illness myopathy. It would therefore be advisable to use it in everyday clinical practice.

We report a case of Miller Fisher syndrome presenting in an ENT setting. The referral was made on the basis of worsening nasal regurgitation following Campylobacter jejuni enteritis. The aim of this report is not to add to the recorded instances of Miller Fisher syndrome, but to help raise the level of its awareness amongst otolaryngologists. Emphasis is placed on the mode of presentation and management issues, as early diagnosis is crucial and confers a favourable prognosis. In that respect, we consider this case noteworthy and instructive.