G. Gronseth

The objective of this report was to develop a case definition of distal symmetric polyneuropathy to standardize and facilitate clinical research and epidemiologic studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetric polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiologic studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach to defining distal symmetric polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiologic research studies will ensure greater consistency of case selection.

Several issues regarding diagnosis, pharmacological treatment, and surgical treatment of trigeminal neuralgia (TN) are still unsettled. The American Academy of Neurology and the European Federation of Neurological Societies launched a joint Task Force to prepare general guidelines for the management of this condition. After systematic review of the literature the Task Force came to a series of evidence-based recommendations. In patients with TN MRI may be considered to identify patients with structural causes. The presence of trigeminal sensory deficits, bilateral involvement, and abnormal trigeminal reflexes should be considered useful to disclose symptomatic TN, whereas younger age of onset, involvement of the first division, unresponsiveness to treatment and abnormal trigeminal evoked potentials are not useful in distinguishing symptomatic from classic TN. Carbamazepine (stronger evidence) or oxcarbazepine (better tolerability) should be offered as first-line treatment for pain control. For patients with TN refractory to medical therapy early surgical therapy may be considered. Gasserian ganglion percutaneous techniques, gamma knife and microvascular decompression may be considered. Microvascular decompression may be considered over other surgical techniques to provide the longest duration of pain freedom. The role of surgery versus pharmacotherapy in the management of TN in patients with multiple sclerosis remains uncertain.

<b>Background:</b> Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standardized, the available literature was reviewed to provide evidence-based guidelines regarding the role of autonomic testing, nerve biopsy, and skin biopsy for the assessment of polyneuropathy. <b>Methods:</b> A literature review using MEDLINE, EMBASE, and Current Contents was performed to identify the best evidence regarding the evaluation of polyneuropathy published between 1980 and March 2007. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based upon the level of evidence. <b>Results and Recommendations:</b> 1) Autonomic testing should be considered in the evaluation of patients with polyneuropathy to document autonomic nervous system dysfunction (Level B). Such testing should be considered especially for the evaluation of suspected autonomic neuropathy (Level B) and distal small fiber sensory polyneuropathy (SFSN) (Level C). A battery of validated tests is recommended to achieve the highest diagnostic accuracy (Level B). 2) Nerve biopsy is generally accepted as useful in the evaluation of certain neuropathies as in patients with suspected amyloid neuropathy, mononeuropathy multiplex due to vasculitis, or with atypical forms of chronic inflammatory demyelinating polyneuropathy (CIDP). However, the literature is insufficient to provide a recommendation regarding when a nerve biopsy may be useful in the evaluation of DSP (Level U). 3) Skin biopsy is a validated technique for determining intraepidermal nerve fiber density and may be considered for the diagnosis of DSP, particularly SFSN (Level C). There is a need for additional prospective studies to define more exact guidelines for the evaluation of polyneuropathy. <b>AAN</b> = American Academy of Neurology; <b>AANEM</b> = American Academy of Neuromuscular and Electrodiagnostic Medicine; <b>AAPM&amp;R</b> = American Academy of Physical Medicine and Rehabilitation; <b>ART</b> = autonomic reflex testing; <b>BRSI</b> = baroreflex sensitivity index; <b>CASS</b> = composite autonomic scoring scale; <b>CIDP</b> = chronic inflammatory demyelinating polyneuropathy; <b>DSFN</b> = distal small fiber neuropathy; <b>DSP</b> = distal symmetric polyneuropathy; <b>EDx</b> = electrodiagnosis; <b>EFNS</b> = European Federation of Neurological Societies; <b>HRV</b> = heart rate variability; <b>IAN</b> = idiopathic autonomic neuropathy; <b>IENF</b> = intraepidermal nerve fibers; <b>MSNA</b> = muscle sympathetic nerve activity; <b>NCSs</b> = nerve conduction studies; <b>PGP 9.5</b> = protein-gene-product 9.5; <b>PN</b> = peripheral neuropathy; <b>PRT</b> = blood pressure recovery time; <b>QAE</b> = quantitative autonomic examination; <b>QSART</b> = quantitative sudomotor axon reflex test; <b>QSS</b> = Quality Standards Subcommittee; <b>QST</b> = quantitative sensory testing; <b>SFSN</b> = small fiber sensory polyneuropathy; <b>TST</b> = thermoregulatory sweat testing.

BACKGROUND: Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standardized, the available literature was reviewed to provide evidence-based guidelines regarding the role of laboratory and genetic tests for the assessment of DSP. METHODS: A literature review using MEDLINE, EMBASE, and Current Contents was performed to identify the best evidence regarding the evaluation of polyneuropathy published between 1980 and March 2007. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based upon the level of evidence. RESULTS AND RECOMMENDATIONS: 1) Screening laboratory tests may be considered for all patients with polyneuropathy (Level C). Those tests that provide the highest yield of abnormality are blood glucose, serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein immunofixation electrophoresis (Level C). If there is no definite evidence of diabetes mellitus by routine testing of blood glucose, testing for impaired glucose tolerance may be considered in distal symmetric sensory polyneuropathy (Level C). 2) Genetic testing should be conducted for the accurate diagnosis and classification of hereditary neuropathies (Level A). Genetic testing may be considered in patients with cryptogenic polyneuropathy who exhibit a hereditary neuropathy phenotype (Level C). Initial genetic testing should be guided by the clinical phenotype, inheritance pattern, and electrodiagnostic features and should focus on the most common abnormalities which are CMT1A duplication/HNPP deletion, Cx32 (GJB1), and MFN2 mutation screening. There is insufficient evidence to determine the usefulness of routine genetic testing in patients with cryptogenic polyneuropathy who do not exhibit a hereditary neuropathy phenotype (Level U).

BACKGROUND: Distal symmetric polyneuropathy (DSP) is the most common variety of neuropathy. Since the evaluation of this disorder is not standardized, the available literature was reviewed to provide evidence-based guidelines regarding the role of autonomic testing, nerve biopsy and skin biopsy for the assessment of polyneuropathy. METHODS: A literature review using MEDLINE, EMBASE, Science Citation Index and Current Contents was performed to identify the best evidence regarding the evaluation of polyneuropathy published between 1980 and March 2007. Articles were classified according to a four-tiered level of evidence scheme and recommendations were based upon the level of evidence. RESULTS AND CONCLUSIONS: 1. Autonomic testing may be considered in the evaluation of patients with polyneuropathy to document autonomic nervous system dysfunction (Level B). Such testing should be considered especially for the evaluation of suspected autonomic neuropathy (Level B) and distal small fiber sensory polyneuropathy (SFSN) (Level C). A battery of validated tests is recommended to achieve the highest diagnostic accuracy (Level B). 2. Nerve biopsy is generally accepted as useful in the evaluation of certain neuropathies as in patients with suspected amyloid neuropathy, mononeuropathy multiplex due to vasculitis, or with atypical forms of chronic inflammatory demyelinating polyneuropathy (CIDP). However, the literature is insufficient to provide a recommendation regarding when a nerve biopsy may be useful in the evaluation of DSP (Level U). 3. Skin biopsy is a validated technique for determining intraepidermal nerve fiber (IENF) density and may be considered for the diagnosis of DSP, particularly SFSN (Level C). There is a need for additional prospective studies to define more exact guidelines for the evaluation of polyneuropathy.