To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
The vasculitic neuropathies are a diverse group of disorders characterised by the acute-to-subacute onset of painful sensory and motor deficits that result from inflammatory destruction of nerve blood vessels and subsequent ischaemic injury. They are common in patients with primary systemic vasculitis and are seen in vasculitis secondary to disorders such as rheumatoid arthritis, viral infections, and diabetic inflammatory neuropathies. It is imperative that neurologists recognise these disorders to initiate treatment promptly and thereby prevent morbidity and mortality. To simplify the approach to patients with vasculitis of the peripheral nerves, a straightforward, dichotomous classification scheme can be used in which the vasculitic neuropathies are divided into two groups-nerve large arteriole vasculitis and nerve microvasculitis-on the basis of the size of the involved vessels. The size of the affected blood vessels correlates with the clinical course and prognosis in patients with vasculitic neuropathy.
The MG-QOL15r is now the preferred HRQOL instrument for MG because of improved clinimetrics and ease of use. This revision does not negate previous studies or interpretations of results using the MG-QOL15. Muscle Nerve 54: 1015-1022, 2016.
The sensory neuronopathies (or ganglionopathies) are a small subcategory of neuropathies characterized by primary degeneration of the dorsal root ganglia and trigeminal ganglion sensory neurons, resulting in a distinctive clinical presentation. Patients typically have subacute onset of asymmetric, non-length-dependent sensory impairment and early ataxia. The etiologies of acquired sensory neuronopathies are rather limited. Early identification is imperative, as they may herald an underlying malignancy or an autoimmune condition such as Sjögren syndrome. This review addresses the various causes of acquired sensory neuronopathies, the recommended diagnostic approach, and treatment options. Finally, I will briefly discuss a select few hereditary and degenerative sensory neuronopathies, which, in contrast to the acquired disorders, are slowly progressive and are usually associated with additional neurological symptoms.
Neuropathies associated with nutritional deficiencies are routinely encountered by the practicing neurologist. Although these neuropathies assume different patterns, most are length‐dependent, sensory axonopathies. Cobalamin deficiency neuropathy is the exception, often presenting with a non–length‐dependent sensory neuropathy. Patients with cobalamin and copper deficiency neuropathy characteristically have concomitant myelopathy, whereas vitamin E deficiency is uniquely associated with a spinocerebellar syndrome. In contrast to those nutrients for which deficiencies produce neuropathies, pyridoxine toxicity results in a non–length‐dependent sensory neuronopathy. Deficiencies occur in the context of malnutrition, malabsorption, increased nutrient loss (such as with dialysis), autoimmune conditions such as pernicious anemia, and with certain drugs that inhibit nutrient absorption. When promptly identified, therapeutic nutrient supplementation may result in stabilization or improvement of these neuropathies.
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