Unfortunately, epidemiological data about causes of peripheral neuropathies in other geographical regions such as Asia or South America are sparse.

Hospital data-based epidemiological studies provide (often differing) lists of most frequent causes of peripheral neuropathy in Western countries (Table 1). Recently, even hereditary neuropathies have entered the “era of treatment in neurology”, with the approval for transthyretin stabilizing agents (tafamidis), RNA interference molecules (patisiran) and antisense oligonucleotids (inotersen) in hereditary transthyretin amyloidosis (ATTR v). For instance, almost every 10th patient suffers from a polyneuropathy of autoimmune origin, which is amenable to causal (immunosuppressive or immunomodulatory) therapies and, therefore, must not be overlooked. The diagnosis of peripheral neuropathy necessitates a thorough workup of possible etiologies in order to identify treatable causes of this disease spectrum as early as possible.

In the USA, it is estimated that patients with idiopathic neuropathies outnumber patients with Alzheimer’s disease up to threefold. Peripheral neuropathies are among the most common neurological diseases with an incidence of 77/100,000 inhabitants per year and a prevalence of 1–12% in all age groups and up to 30% in older people. This two-tiered approach promises higher yield and better cost-effectiveness in the diagnostic workup in patients with peripheral neuropathy. The recognition of characteristic clinical phenotypes combined with nerve conduction studies allows pursuing subsequent diagnostic pathways that incorporate nerve conduction studies and additional diagnostic tests. Based on these five clinical phenotypes, we suggest differential diagnostic pathways in order to establish the underlying cause. We propose a flow chart based on five common basic clinical patterns of peripheral neuropathy. Laboratory tests, including genetic testing, CSF examination, nerve imaging, and nerve biopsy, represent additional clinical tests that can be useful in specific clinical scenarios. Nerve conduction studies are essential to determine the phenotype (axonal versus demyelinating) and severity. The variability of symptoms allows distinguishing characteristic clinical phenotypes of peripheral neuropathy that should be recognized in order to stratify the diagnostic workup accordingly.

A thorough workup including clinical history and examination, nerve conduction studies, and comprehensive laboratory tests is warranted to identify treatable causes. The most common causes are diabetes, exposure to toxic substances including alcohol and chemotherapeutics, immune-mediated conditions, and gene mutations. Peripheral neuropathy represents a spectrum of diseases with different etiologies.

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