Drug-induced peripheral neuropathies

Review of the various drugs in current clinical use showed that over 50 of them may cause a purely sensory or mixed sensorimotor neuropathy. These include antimicrobials, such as isoniazid, ethambutol, ethionamide, nitrofurantoin, and metronidazole; antineoplastic agents, particularly vinca alkaloids; cardiovascular drugs, such as perhexiline and hydrallazine; hypnotics and psychotropics, notable methaqualone; antirheumatics, such as gold, indomethacin, and chloroquine; anticonvulsants, particularly phenytoin; and other drugs, including disulfiram, calcium carbimide, and dapsone. Patients receiving drug treatment who complain of paraesthesie, pain, muscle cramps, or other abnormal sensations and those without symptoms who are receiving drugs that are known or suspected to be neurotoxic should undergo neurological examination and studies of motor and sensory nerve conduction. This will allow the incidence of drug-induced peripheral neuropathy to be determined more precisely

Intramedullary spinal cord metastasis from mammary carcinoma

Metastases to the substance of the spinal cord are almost certainly more frequent than generally supposed. The majority of previously reported cases have been bronchogenic primaries and only three have been from mammary carcinomas. The case of a 47-year-old woman who became paraplegic eight years after radical mastectomy for carcinoma of the breast is reported. An episode of herpes zoster in the fourth thoracic dermatome preceded the onset of paraplegia. At necropsy there were widespread metastases in many organs. A solitary metastasis was found in the thoracic cord extending from T3 to T6 and extending into a dorsal nerve root at T4

Cytokines in immune-mediated inflammatory myopathies: Cellular sources, multiple actions and therapeutic implications

The idiopathic inflammatory myopathies are a heterogeneous group of disorders characterised by diffuse muscle weakness and inflammation. A common immunopathogenic mechanism is the cytokine driven infiltration of immune cells into the muscle tissue. Recent studies have dissected further the inflammatory cell types and associated cytokines involved in the immune-mediated myopathies and other chronic inflammatory and autoimmune disorders. In this review we outline the current knowledge of cytokine expression profiles and cellular sources in the major forms of inflammatory myopathy and detail the known mechanistic functions of these cytokines in the context of inflammatory myositis. Furthermore, we discuss how the application of this knowledge may lead to new therapeutic strategies for the treatment of the inflammatory myopathies, in particular for cases resistant to conventional forms of therapy

The role of interleukin-17 in immune-mediated inflammatory myopathies and possible therapeutic implications

The idiopathic inflammatory myopathies are a heterogeneous group of autoimmune muscle disorders with distinct clinical and pathological features and underlying immunopathogenic mechanisms. Traditionally, CD4+ Th1 cells or CD8+ cytotoxic effector T cells and type I/II interferons have been primarily implicated in the pathogenesis of the inflammatory myopathies. The presence of IL-17A producing cells in the inflamed muscle tissue of myositis patients and the results of in vitro studies suggest that IL-17A and the Th17 pathway may also have a key role in these diseases. The contribution of IL-17A to other chronic inflammatory and autoimmune diseases has been well established and clinical trials of IL-17A inhibitors are now at an advanced stage. However the precise role of IL-17A in the various forms of myositis and the potential for therapeutic targeting is currently unknown and warrants further investigation

Synucleinopathy in amyotrophic lateral sclerosis: A potential avenue for antisense therapeutics?

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease classified as both a neurodegenerative and neuromuscular disorder. With a complex aetiology and no current cure for ALS, broadening the understanding of disease pathology and therapeutic avenues is required to progress with patient care. Alpha-synuclein (αSyn) is a hallmark for disease in neurodegenerative disorders, such as Parkinson’s disease, Lewy body dementia, and multiple system atrophy. A growing body of evidence now suggests that αSyn may also play a pathological role in ALS, with αSyn-positive Lewy bodies co-aggregating alongside known ALS pathogenic proteins, such as SOD1 and TDP-43. This review endeavours to capture the scope of literature regarding the aetiology and development of ALS and its commonalities with “synucleinopathy disorders”. We will discuss the involvement of αSyn in ALS and motor neuron disease pathology, and the current theories and strategies for therapeutics in ALS treatment, as well as those targeting αSyn for synucleinopathies, with a core focus on small molecule RNA technologies

Enterovirus hypothesis for motor neurone disease

Letter to the Edito

Sleep disordered breathing and subclinical impairment of respiratory function are common in sporadic inclusion body myositis

Relatively little is known about frequency and extent of respiratory problems in sporadic inclusion body myositis (IBM). To address this issue a study of peripheral muscle and respiratory function and related symptoms was performed in a cohort with biopsy-proven IBM. Dyspnoea, daytime sleepiness, dysphagia, spirometry, respiratory muscle strength, arterial blood gas tensions and ventilation during sleep were assessed. Sixteen patients were studied (10 males; age 68.1 ± 9.9 years; disease duration 11.9 ± 5.0 years; body mass index 28.5 ± 4.0 kg/m2). Four reported excessive daytime sleepiness; 8 had at least mild dysphagia; forced vital capacity was <80% predicted normal in 7; sniff nasal inspiratory pressure was reduced in 3; daytime hypoxemia was present in 9 and hypercapnia in one. Sleep study was performed in 15 and revealed sleep disordered breathing (apnoea–hypopnoea index 23.4 ± 12.8 (range 7–50.3) events/h) in all. There were no consistent relationships between respiratory function impairment, occurrence of sleep disordered breathing, and severity of peripheral muscle weakness. Thus, asymptomatic impairment of respiratory function was common and sleep disordered breathing observed in all patients tested, irrespective of daytime respiratory function. This suggests respiratory function testing, including sleep study, should be performed routinely in IBM, irrespective of peripheral muscle function or other disease severity parameters

Targeted molecular therapeutics for Parkinson's Disease: A role for antisense oligonucleotides?

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by marked heterogeneity in clinical symptoms and a complex genetic background..

Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset

Neurofilament heavy (NEFH) is one of the critical proteins required for the formation of the neuronal cytoskeleton and polymorphisms in NEFH are reported as a rare cause of sporadic ALS (sALS). In the current study, a candidate tetranucleotide (TTTA) repeat variant in NEFH was selected using an in-silico short structural variant (SSV) evaluation algorithm and investigated in two cohorts of North American sALS patients, both separately and combined (Duke cohort n = 138, Coriell cohort n = 333; combined cohort n = 471), compared to a group of healthy controls from the Coriell Institute biobank (n = 496). Stratification according to site of disease onset revealed that the 9 TTTA allele was associated with reduced disease risk, specifically confined to spinal-onset sALS patients in the Duke cohort (p = 0.001). Furthermore, carriage of the 10 TTTA allele was associated with a 2.7 year later age of disease onset in the larger combined sALS cohort (p = 0.02). These results suggest that the 9 and 10 TTTA motif length may have a protective advantage for potentially lowering the risk of sALS and delaying the age of disease onset, however, these results need to be replicated in larger multicenter and multi-ethnic cohorts