Guidelines e3 Diagnosis of Polyneuropathies Guidelines of the German Society of Neurology Authors D. Heuß1, M. Auer−Grumbach2, W. F. Haupt3, W. Löscher4, B. Neundörfer5, B. Rautenstrauß6, S. Renaud7, C. Sommer8 Affiliations The affiliations are listed at the end of the article. Keywords Abstract What’s new? l" polyneuropathies ! ! l" definition The most important recommendations at a " Mitofusin−2−(MFN2−)mutations are the most l" manifestation types glance: History and clinical findings provide the common cause of CMT 2 neuropathies (Ver− l" clinical examination most important data for the classification of hoeven et al. 2006) (III) (B). l" differential diagnosis polyneuropathies (familial, acute versus chronic " Antibodies to MAG or SGPG occur frequently l" neurophysiological examination course, concomitant disease; involved organ sys− in patients with IgM amyloidosis but their l" muscle and nerve biopsy tems, symmetrical versus multifocal etc.) (IV) (C). presence alone does not predict occurrence or l" skin biopsy Electrophysiological examination is necessary to type of polyneuropathy (Garces−Sanchez et al. l" genetic testing determine the pattern of distribution and the 2008) (III) (B). l" laboratory tests type of lesion (axonal versus demyelinating) in " Several new or recently established methods order to detect specific patterns of damage (e.g. facilitate the diagnosis of small−fiber neuro− conduction blocks) and to assess the resulting pathy which is not detectable by conventional degree of muscle damage (¹denervation“) (B). electrophysiological methods (Sommer and Laboratory tests should include the most impor− Lauria 2007) (III) (B). tant treatable polyneuropathies (see below) (C). " Ultrasound and MRI examinations are helpful The examination of CSF is useful in the differen− in the diagnosis of neuropathies according to tial diagnosis of inflammatory polyneuropathies preliminary studies (Bendszus and Stoll 2005, (B). Nodera et al. 2006, Ito et al. 2007) (III) (B). Genetic examinations are warranted in the case " Serum holo−transcobalamin (HoloTC) is the of a positive family history for polyneuropathy earliest marker of vitamin B deficiency (Herr− or in the presence of typical signs of hereditary mann et al. 2005, Obeid and Herrmann 2007) polyneuropathy (pes cavus or hammer toes). (IIa) (B). Nerve biopsies are recommended in the case of " Serum holo−transcobalamin levels following suspected treatable polyneuropathy that cannot oral application of vitamin B12 is suitable to be diagnosed by other means (e.g. vasculitis, examine the resorption on vitamin B12 (Bor et atypical CIDP, amyloidosis). Nerve biopsies al. 2004, Bor et al. 2005) (III) (B). This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. should be performed and analysed only in spe− cialized centers (C). Bibliography When considering small fiber neuropathy, quan− DOI 10.1055/s−0029−1220453 titative sensory testing and quantification of skin Akt Neurol 2009; 36: e3±e13 innervation are helpful diagnostic instruments. Georg Thieme Verlag KG Stuttgart ´ New York ´ ISSN 0302−4350 Definition cells, their connective tissue cover structures Corresponding author ! (peri− and epineurium) and their supplying blood Prof. Dr. Dieter Heuß Polyneuropathies (PNP) (Dyck et al. 1993, Men− and lymphatic vessels which lie outside of the Neuromuskuläres Zentrum, dell et al. 2001, Neundörfer and Heuß 2006, central nervous system (CNS) belong to the PNS. Neurologische Klinik des Uni− Pestronk 2008) are generalised diseases of the versitätsklinikums Erlangen Schwabachanlage 6 peripheral nervous system (PNS). All elements of 91054 Erlangen the motor, sensory, and autonomic nerves with dieter.heuss@uk−erlangen.de their Schwann cells and ganglionary satellite Heuß D et al. Diagnosis of Polyneuropathies¼ Akt Neurol 2009; 36: e3±e13 e4 Guidelines Figure 1 Distribution of etiology in 1195 patients Diabe t e s 34,8 with polyneuropathy (Engelhardt 1994). U nk no wn 22,0 Alk oholism 11,1 AIDS (GB S) 6,3 Inf ec t ion 5,4 V a s c ulit is 4,1 CIDP 4,1 Mal ab sor p t ion 3,8 P ar ane opl a sia 2,7 CMT 2,2 P ar a pro t einemia 1,1 T o xin 0,9 Am y l oid osis 0,5 HNP P 0,2 Ot her 0,9 0 10 20 30 40 General principles of diagnostics " Muscle weakness ! " Muscle atrophy The basic and complementary examinations in the diagnosis of polyneuropathies can be classified as: Loss of autonomic function " Obligatory examinations See l" table 1 " History " Clinical examination Specific history " Neurophysiological examinations Course and duration of complaints " Standard laboratory examinations The course of disease is relevant for the diagnosis " Facultative examinations " <4 weeks: acute " Extended laboratory tests " 4±8 weeks: subacute " CSF examination " <8 weeks: chronic " Biopsy of muscle, nerve, or skin Examples: Guillain−BarrØ syndrome (GBS) acute, chronic inflam− " Genetic examinations matory demyelinating polyneuropathy (CIDP) acute to subacute, hereditary motor and sensory polyneuropathy (CMT) chronic with positive family history Clinical diagnostics ! Cave The clinical diagnosis of a polyneuropathy is based on the his− vasculitic polyneuropathies can develop over years and in− tory, symptoms reported by the patient, and on the clinical signs. filtration of the PNS with lymphoma cells (neurolympho− matosis) can present as an acute axonal or demyelinating Important questions in history taking polyneuropathy. Sensory plus−symptoms and deficits " Tingling " Pins and needles sensations Questions concerning impairment or concomitant " Warm and cold paraesthesias diseases This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. " Stabbing pain " Sports abilities as a child, problems when purchasing shoes " Electrifing feeling " Frequent stumbling (distal weakness?) " Numbness " Trouble when rising from low chairs, from squatting and " Feeling of constriction when climbing stairs (proximal weakness) " Swollen feeling " Other diseases which might cause polyneuropathies " Feeling of unpleasant pressure (diabetes, kidney disease, collagenosis, malignant disease) " Feeling of walking on cotton (l" Fig.1) " Unstable gait, especially in the dark " Operations (laminectomy etc.) " Loss of temperature sensation " History of medications, illicit drugs, toxins, especially alcohol " Painless skin injuries consumption (Neundörfer 2006) Motor irritation and loss of function phenomena Medication−induced polyneuropathies: Aside from the well− " Fasciculations known potentially polyneuropathy−inducing medications (che− " Muscle contractions motherapy agents, INH, thalidomide, etc.) polyneuropathies " Muscle cramps have been described due to other medications, previously not Heuß D et al. Diagnosis of Polyneuropathies ¼ Akt Neurol 2009; 36: e3±e13 Guidelines e5 known to be neurotoxic. Statins in some cases produce sensory Table 1 Results of autonomic nerve tests. and sensomotor polyneuropathies after long−term application which are reversible after discontinuation of the statin (de Lan− Effects of efferent autonomic denervation Somatic nerves gen and van Puijenbroek 2006). Bortezomib (Velcade), a new ± Pupillary abnormalities protease−inhibitor, which is used in the treatment of multiple ± Trophic disturbances: edema, ulcers, osteoarthropathy myeloma, causes painful sensorimotor polyneuropathies which ± Hyp− and anhidrosis are only partially reversible (Richardson et al. 2006). Linezolid, ± Vasomotor dysfunction: othostatic hypotension, rubeosis plantarum a new antibiotic of the oxazolidine group, produces a painful Visceral nerves sensorimotor polyneuropathy after long−term application and a ± Cardiovascular: resting tachycardia, unmodulated heart rate toxic opticopathy (Bressler et al. 2004, Rucker et al. 2006). Also, ± Gastrointestinal: dystonia of oesophagus, gastric paresis, diarrhea, medications which are used in the treatment of neuropathies obstipation, gall bladder dysfunction such as rituximab or tumor necrosis factor blockers, can cause ± Liver: disturbance of glucose metabolism polyneuropathies in rare cases (Richez et al. 2005, Mauermann ± Exocrine pancreatic function: loss of reflectory secretion et al. 2007). ± Urogenital: Loss of bladder control, erectile dysfunction, retrograde ejaculation Systems review Effects of afferent autonomic denervation ± Loss of pain in cardiac ischemia " Diminished perspiration of extremities or compensatory ± Loss of vegetative reaction in hypoglycaemia perspiration of the trunk ± Loss of bladder filling sensation " Disturbances of bowel or bladder function ± Loss of scrotal pain " Erectile dysfunction ± Loss of labor pain " Joint pain " Dermatological signs " Syncopes Table 2 Polyneuropathies with autonomic involvement (modified after McDougall and McLeod 1996). Family history Pronounced autonomic involvement Ask expressly for disturbances of gait, foot deformities, atrophic ± Acute pandysautonomia (thin) calves ± Diabetic polyneuropathy ± Polyneuropathy in amyloidosis General examination ± GBS " Skeletal abnormalities: pes cavus, flat feet, hammer toes, ± Porphyric polyneuropathy scoliosis, kyphosis, Charcot arthropathy, pathological frac− ± Hereditary sensory−autonomic neuropathy (HSAN) type III tures (familial dysautonomia, Riley−Day syndrome) " Organomegaly ± Hereditary sensory−autonomic neuropathy (HSAN) type IV " Alterations of the skin and skin appendages: ulcers, pigmen− ± Paraneoplastic polyneuropathy tation changes, purpura, loss of leg hair, alopecia, curved nails,