Small and large fiber sensory polyneuropathy in type 2 diabetes: Influence of diagnostic criteria on neuropathy subtypes.

Diabetic polyneuropathy (DPN) can be classified based on fiber diameter into three subtypes: small fiber neuropathy (SFN), large fiber neuropathy (LFN), and mixed fiber neuropathy (MFN). We examined the effect of different diagnostic models on the frequency of polyneuropathy subtypes in type 2 diabetes patients with DPN. This study was based on patients from the Danish Center for Strategic Research in Type 2 Diabetes cohort. We defined DPN as probable or definite DPN according to the Toronto Consensus Criteria. DPN was then subtyped according to four distinct diagnostic models. A total of 277 diabetes patients (214 with DPN and 63 with no DPN) were included in the study. We found a considerable variation in polyneuropathy subtypes by applying different diagnostic models independent of the degree of certainty of DPN diagnosis. For probable and definite DPN, the frequency of subtypes across diagnostic models varied from: 1.4% to 13.1% for SFN, 9.3% to 21.5% for LFN, 51.4% to 83.2% for MFN, and 0.5% to 14.5% for non-classifiable neuropathy (NCN). For the definite DPN group, the frequency of subtypes varied from: 1.6% to 13.5% for SFN, 5.6% to 20.6% for LFN, 61.9% to 89.7% for MFN, and 0.0% to 6.3% for NCN. The frequency of polyneuropathy subtypes depends on the type and number of criteria applied in a diagnostic model. Future consensus criteria should clearly define sensory functions to be tested, methods of testing, and how findings should be interpreted for both clinical practice and research purpose.

Chronic inflammatory axonal polyneuropathy.

OBJECTIVES: Chronic inflammatory axonal polyneuropathy (CIAP) is defined on the basis of the clinical, electrophysiological and nerve biopsy findings and therapeutic responses of 'immunotherapy responding chronic axonal polyneuropathy (IR-CAP)'. METHODS: The diagnosis of IR-CAP was made when all of three of the following mandatory criterion were met: (1) acquired, chronic progressive or relapsing symmetrical or asymmetrical polyneuropathy with duration of progression >2 months; (2) electrophysiological evidence of axonal neuropathy in at least two nerves without any evidence of 'strict criteria of demyelination'; and (3) definite responsiveness to immunotherapy. RESULTS: Thirty-three patients with IR-CAP showed similar clinical features of chronic inflammatory demyelinating polyneuropathy (CIDP) except 'motor neuropathy subtype'. High spinal fluid protein was found in 27/32 (78%) cases. 'Inflammatory axonal neuropathy' was proven in 14 (45%) of 31 sural nerve biopsies. DISCUSSIONS: IR-CAP could well be 'axonal CIDP' in view of clinical similarity, but not proven as yet. Thus, IR-CAP is best described as CIAP, a distinct entity that deserves its recognition in view of responsiveness to immunotherapy. CONCLUSION: Diagnosis of CIAP can be made by additional documentation of 'inflammation' by high spinal fluid protein or nerve biopsy in addition to the first two diagnostic criteria of IR-CAP.

ICU-acquired weakness: should medical sovereignty belong to any specialist?

ICU-acquired weakness (ICUAW), including critical illness polyneuropathy, critical illness myopathy, and critical illness polyneuropathy and myopathy, is a frequent disabling disorder in ICU subjects. Research has predominantly been performed by intensivists, whose efforts have permitted the diagnosis of ICUAW early during an ICU stay and understanding of several of the pathophysiological and clinical aspects of this disorder. Despite important progress, the therapeutic strategies are unsatisfactory and issues such as functional outcomes and long-term recovery remain unclear. Studies involving multiple specialists should be planned to better differentiate the ICUAW types and provide proper functional outcome measures and follow-up. A more strict collaboration among specialists interested in ICUAW, in particular physiatrists, is desirable to plan proper care pathways after ICU discharge and to better meet the health needs of subjects with ICUAW.

Working hand syndrome: A new definition of non-classified polyneuropathy condition.

The aim of this paper was to define an unexplained non-classified polyneuropathy condition as a new neurological disease. This new diagnosis of occupation related polyneuropathy has been named as "WORKING HAND SYNDROME (WHS)."This study collected and compared clinic and electrophysiological analyze data from healthy controls, WHS patients, carpal tunnel syndrome (CTS) patients and polyneuropathy patients. The WHS patients presented to the clinic with pain, numbness, tingling, and burning sensations in their hands that increased significantly during rest and nighttime. However, there was no weakness in the muscles, and the deep tendon reflexes were normal in this disease. The patients had all been working in physically demanding jobs requiring the use of their hands/arms for at least 1 year, but no vibrating tools were used by the patients. All of the cases were men. I supposed that overload caused by an action repeated chronically by the hand/arm may impair the sensory nerves in mentioned hand/arm. In patients with these complaints, for a definitive diagnosis, similar diseases must be excluded. Nonetheless, the specific electrophysiological finding that the sural nerves are normal on the lower sides, as well as the occurrence of sensory axonal polyneuropathy in the sensory nerves without a significant effect on velocity and latency in the work-ups of the upper extremity are enough to make a diagnosis.In conclusion, WHS has been defined as a polyneuropathy and occupational disease. Patients with WHS present with pain, numbness, tingling, and burning sensations in their hands that increases significantly during rest and nighttime. They also use their arms/hands for jobs that require heavy labor. The neurological examinations of patients with WHS are normal. Only the sensory nerves in the upper extremities are affected. This article is suggested to serve as a resource for patients, health care professionals, and members of the neurology community at large.

The nonsystemic vasculitic neuropathies.

Nonsystemic vasculitic neuropathy (NSVN) is an under-recognized single-organ vasculitis of peripheral nerves that can only be diagnosed with a nerve biopsy. A Peripheral Nerve Society guideline group published consensus recommendations on the classification, diagnosis and treatment of NSVN in 2010, and new diagnostic criteria for vasculitic neuropathy were developed by the Brighton Collaboration in 2015. In this Review, we provide an update on the classification, diagnosis and treatment of NSVN. NSVN subtypes include Wartenberg migratory sensory neuropathy and postsurgical inflammatory neuropathy. Variants include diabetic radiculoplexus neuropathy and - arguably - neuralgic amyotrophy. NSVN with proximal involvement is sometimes termed nondiabetic lumbosacral radiculoplexus neuropathy. Cutaneous polyarteritis nodosa and other skin-nerve vasculitides overlap with NSVN clinically. Three patterns of involvement in NSVN have been identified: multifocal neuropathy, distal symmetric polyneuropathy, and overlapping multifocal neuropathy (asymmetric polyneuropathy). These patterns lack standard definitions, resulting in inconsistencies between studies. We propose definitions and provide an up-to-date differential diagnosis of multifocal neuropathy. Available evidence suggests that NSVN and neuropathy-predominant systemic vasculitis might be controlled better by treatment with corticosteroids and an immunosuppressive agent than with corticosteroids alone. Treated NSVN rarely spreads to other organs, but 30% of patients experience a relapse. Long-term neurological outcome is favourable, but chronic pain is common.

Cellular infiltrates in skin and sural nerve of patients with polyneuropathies.

INTRODUCTION: The aim of this study was to determine the diagnostic usefulness of skin punch biopsies with emphasis on visualization and quantification of T-cells and macrophages in patients with polyneuropathies. METHODS: We quantified inflammatory cells in skin samples (lower leg, upper thigh) in 187 patients and compared data with counts in their sural nerve biopsies and with skin biopsies from 32 healthy volunteers. RESULTS: Vessel-bound T-cells and macrophages were increased in proximal and distal skin samples of neuropathy patients compared with controls (P < 0.001 in both). Patients with vasculitic neuropathy had increased T-cell and macrophage counts in distal skin compared with controls (P < 0.01; for scattered macrophages/mm2 diagnostic sensitivity 71% and specificity 79%). In patients with vasculitic neuropathy, distal skin perivascular inflammatory cell counts also correlated with those in sural nerve biopsies (P < 0.001). CONCLUSION: Neuropathy per se may lead to skin inflammation. In cases of possible vasculitic neuropathy, skin biopsy may be an additional tool to support the diagnosis. Muscle Nerve 55: 884-893, 2017.

The Ultrasound pattern sum score - UPSS. A new method to differentiate acute and subacute neuropathies using ultrasound of the peripheral nerves.

OBJECTIVE: Ultrasound differentiation of neuropathies is a great challenge. We, therefore, suggest a standardized score to operationalize differentiation between several acute and subacute onset neuropathies. METHOD: We retrospectively analyzed the ultrasound data of 61 patients with acute or subacute neuropathies, e.g. chronic immune-mediated neuropathies, Guillain-Barré syndrome (GBS), and axonal/vasculitic neuropathies. We compared these data to 28 healthy controls. Based on these results an ultrasound pattern sum score (UPSS) with three sub-scores (UPS-A for the sensorimotor nerves, UPS-B for the cervical roots and the vagal nerve and UPS-C for the sural nerve) was developed. Afterwards, the applicability of the score was prospectively validated in 10 patients with chronic neuropathies and in 14 patients with unknown acute and subacute PNP before performing additional tests. RESULTS: UPS-A and UPSS were significantly higher in CIDP than in other neuropathies and controls (p<0.001). UPS-B was significantly more often pathologic in GBS than in CIDP and other neuropathies (p<0.001). Using receiver operation characteristics curve analysis boundary values for each score were defined. Positive predictive value (PPV) of these scores for CIDP and GBS was >85%. Vasculitic neuropathies showed an intermediate type of UPSS compared to other axonal neuropathies (p<0.001). In the prospective application the pattern score could be used with good accuracy in several types of neuropathy. CONCLUSION: UPS-A and UPSS operationalize to diagnose acute and subacute-onset CIDP and its variants with high sensitivity, specificity, and PPV. An increased UPS-B with normal UPSS and other sub scores may point to the diagnosis of GBS with high PPV and enables the differentiation from CIDP. SIGNIFICANCE: Using the UPSS and its sub-scores gives a new diagnostic power to the method of the peripheral nerve ultrasound.

Multifocal motor neuropathy, multifocal acquired demyelinating sensory and motor neuropathy, and other chronic acquired demyelinating polyneuropathy variants.

Chronic acquired demyelinating neuropathies (CADP) constitute an important group of immune neuromuscular disorders affecting myelin. This article discusses CADP with emphasis on multifocal motor neuropathy, multifocal acquired demyelinating sensory and motor neuropathy, distal acquired demyelinating symmetric neuropathy, and less common variants. Although each of these entities has distinctive laboratory and electrodiagnostic features that aid in their diagnosis, clinical characteristics are of paramount importance in diagnosing specific conditions and determining the most appropriate therapies. Knowledge regarding pathogenesis, diagnosis, and management of these disorders continues to expand, resulting in improved opportunities for identification and treatment.

Natura non facit saltus in anti-ganglioside antibody-mediated neuropathies.

Natura non facit saltus (Latin for "nature does not make jumps") is a maxim expressing the idea that natural things and properties change gradually, in a continuum, rather than suddenly. In biomedical sciences, for taxonomic purposes, we make jumps that emphasize differences more than similarities. Among the dysimmune neuropathies, 2 disorders, characterized by the presence of antibodies to gangliosides GM1 and GD1a and a peculiar, exclusive motor involvement, have been identified: acute motor axonal neuropathy (AMAN) and multifocal motor neuropathy (MMN). However, anti-GM1 or -GD1a antibodies are also associated with acute motor and sensory axonal motor neuropathy (AMSAN). We review the results of recent clinical and experimental studies showing that AMAN and MMN are not exclusively motor. We discuss the possible explanations for the greater resistance of sensory fibers to antibody attack to finally suggest that AMAN, AMSAN, and MMN belong to a continuous spectrum with a common pathophysiological mechanism.

[Genetics of neuropathies]. / Genetik der Neuropathien.

Hereditary neuropathies belong to the most common neurogenetic disorders. They appear mostly as sensory and motor neuropathies but there are also pure sensory, pure motor as well as sensory and autonomic hereditary neuropathies. In clinical practice, knowledge of hereditary neuropathies is important in order to recognize them among polyneuropathies and achieve a successful genetic diagnosis. The molecular genetics of hereditary neuropathies are very heterogeneous with currently more than 40 known disease-causing genes. The 4 most common genes account for almost 90% of the genetically diagnosed hereditary neuropathies. In this review article we provide an overview of the currently known genes and propose a rational genetic work-up protocol of the most common genes.

Capturing cases of distal symmetric polyneuropathy in a community.

INTRODUCTION: Little is known about what constitutes appropriate diagnostic testing in patients with distal symmetric polyneuropathy (DSP). METHODS: Utilizing an ICD-9 screening method and medical record abstraction, we determined the number of new cases of DSP within community neurology practices in Nueces County, Texas. We then compared 2 case capture methods (ICD-9 vs. all-case review screening). RESULTS: The ICD-9 case capture method identified 52 cases over a 3-month period. Comparing case capture methods, the ICD-9 method identified 16 of 17 cases identified by the all-case review method (94%). The ICD-9 method required screening of 84% fewer charts compared with the all-case review. CONCLUSIONS: Many new cases of DSP occur each month within Nueces County. The ICD-9 screening technique combined with medical abstraction is an efficient method to identify new DSP cases in this community. These findings are critical for future epidemiological investigations into patients with DSP.

[Demyelinating polyneuropathies in patients with diabetes mellitus and chronic alcoholic intoxication].

Frequency and nosological attribution of demyelinating polyneuropathies in patients with diabetes mellitus and alcoholism were determined. Eighty-six inpatients with alcoholic (n=46) and diabetic (n=40) polyneuropathy were examined clinically and using electroneuromyography (ENMG). A demyelinating pathogenetic variant was identified by clinical and ENMG data in 27 (31%) patients. Nine patients (33%) had dysimmune polyneuropathies (acute and chronic inflammatory demyelinating polyneuropathy). Polyneuropathies were specified as toxic/metabolic with the prevalence of a demyelinating component within the main disease in 18 (67%) patients. Clinical and ENMG-signs of the demyelinating variant of alcoholic and diabetic neuropathy are presented. The efficacy of the antioxidant berlition was shown for toxic/metabolic polyneuropathies while the addition of immune modulators was needed for treatment of dysimmune polyneuropathy.

A common mechanism and a new categorization for anti-ganglioside antibody-mediated neuropathies.

Serum antibodies to different gangliosides have been identified in some Guillain-Barré (GBS) subtypes and variants. In the January issue of Experimental Neurology Susuki and colleagues (2012) showed that in experimental neuropathies associated with antibodies to GM1, GD1a and GD1b the common mechanism is a complement mediated dysfunction and disruption of the nodes of Ranvier which causes a pathophysiological continuum from early reversible conduction failure to axonal degeneration. These observations, correlated and integrated with electrophysiological and pathological findings in humans indicate that the GBS subtypes acute motor conduction block neuropathy, acute motor axonal neuropathy, acute motor and sensory neuropathy and acute sensory neuropathy and possibly also a chronic disorder as multifocal motor neuropathy represent a spectrum of the same immunopathologic process. Being the nodal axolemma and the paranode the focus of the nerve injury, these immune mediated neuropathies could be more properly classified as nodo-paranodopathies.

Median nerve ultrasonography in distinguishing neuropathy sub-types: a pilot study.

BACKGROUND: The diagnostic potential of ultrasonography (US) in polyneuropathy has been studied rarely, with complex measurement/correction techniques. Whether US may be useful in clinical practice remains uncertain. MATERIALS AND METHODS: We aimed to ascertain the value of US, as performed routinely at our institution, in differentiating neuropathy sub-types. We prospectively studied 14 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 14 patients with sensory axonal neuropathy (SAN). Median nerves were studied bilaterally at wrist and forearm by a radiologist blinded to the neuropathy sub-type. Nerve width (medial to lateral diameter), thickness (anterior to posterior diameter) and cross-sectional area were compared in between patient groups and anatomical sites. Optimal cut-off values were determined using receiver operating characteristic (ROC) curves. RESULTS: Largest measured median nerve thickness was significantly greater in patients with CIDP (P = 0.014), and ROC curve analysis indicated a cut-off offering a sensitivity of 57.1% for CIDP and specificity of 92.9% vs SAN. Nerves were wider and had larger cross-sectional areas, but were not thicker, at wrist compared to forearm in both patient groups. There was an equal prevalence in both patients with CIDP and SAN, of increased median nerve wrist-to-forearm area ratio, compatible with sub-clinical carpal tunnel syndrome. CONCLUSION: This prospective, blinded, pilot study is the first to indicate the diagnostic potential of US, as performed routinely, in distinguishing between acquired demyelinating and axonal neuropathy. These findings now require confirmation in larger, adequately designed studies, evaluating other nerves/nerve sites, assessing healthy controls and taking into account interrater and equipment variabilities.

[Diagnosis of immune-mediated neuropathies]. / Az immunmediált neuropathiák diagnosztikája.

Separate discussion of immune-mediated neuropathies from other neuropathies is justified by the serious consequences of the natural course of these diseases, like disability and sometimes even life threatening conditions. On the other hand nowadays effective treatments already exist, and with timely and correct diagnosis an appropriately chosen treatment may result in significant improvement of quality of life, occasionally even complete recovery. These are rare diseases, and the increasing number of different variants makes it more difficult to recognize them. Their diagnosis is based on the precise knowledge of clinical signs and symptoms, and it is verified by the help of neurophysiologic and laboratory, first of all CSF examinations. Description of clinical features of the classic acute immune-mediated neuropathy, characterized by ascending paresis and demyelination is followed by a summary of characteristics of newly recognized axonal, regional and functional variants. Chronic immune-mediated demyelinating polyneuropathies are not diagnosed in due number even today. This paper does not only present the classic form but it also introduces the ever increasing special variants, like distal acquired demyelinating sensory neuropathy, Lewis-Sumner syndrome, multifocal motor neuropathy and paraproteinemic neuropathies. Vasculitic neuropathies can be divided into two groups: systemic and non-systemic ones. The first sign of a vasculitic neuropathy is a progressive, painful mononeuropathy; the classic clinical presentation is the mononeuritis multiplex. It is characterized by general signs like fever, loss of weight, fatigue. In systemic vasculitis organ specific symptoms are also present. From the paraneoplastic diseases the subacute sensory neuropathy and the sensory neuronopathy are members of the immune-mediated neuropathies, being most frequently associated with small cell lung cancer.

Parálisis flacida aguda, una presentación atípica del sindrome de Guillain Barre / Acute flaccid paralysis, an atypical presentation of Guillain Barre Syndrome

El s índrome de Guillain Barr é es una polineuropatia postinfecciosa que afecta principalmente a los nervios motores, pero en ocasiones afecta tambi én a los nervios sensitivos y aut ónomos. Este s índrome se puede presentar en personas de todas las edades y no es hereditario, su diagnó stico es esencialmente descriptivo siendo muy importante una buena anamnesis y un buen examen f ísico apoy ándose en estudios de conducci ón nerviosa. El objetivo de esta publicaci ón es la presentaci ón de un caso clínico de un paciente pe diátrico que ingresa a la unidad de cuidados intensivos del IHSS con una forma de presentaci ón at ípica de esta patologí a y una evoluci ón y deterioro clínico r ápido. ...(AU)

Is reflex sympathetic dystrophy/complex regional pain syndrome type I a small-fiber neuropathy?

Neurologist S. Weir Mitchell first described "causalgia" following wartime nerve injury, with its persistent distal limb burning pain, swelling, and abnormal skin color, temperature, and sweating. Similar post-traumatic symptoms were later identified in patients without overt nerve injuries after trauma. This was labeled reflex sympathetic dystrophy (RSD; now complex regional pain syndrome type I [CRPS-I]). The pathophysiology of symptoms is unknown and treatment options are limited. We propose that persistent RSD/CRPS-I is a post-traumatic neuralgia associated with distal degeneration of small-diameter peripheral axons. Small-fiber lesions are easily missed on examination and are undetected by standard electrophysiological testing. Most CRPS features-spreading pain and skin hypersensitivity, vasomotor instability, osteopenia, edema, and abnormal sweating-are explicable by small-fiber dysfunction. Small fibers sense pain and temperature but also regulate tissue function through neuroeffector actions. Indeed, small-fiber-predominant polyneuropathies cause CRPS-like abnormalities, and pathological studies of nerves from chronic CRPS-I patients confirm small-fiber-predominant pathology. Small distal nerve injuries in rodents reproduce many CRPS features, further supporting this hypothesis. CRPS symptoms likely reflect combined effects of axonal degeneration and plasticity, inappropriate firing and neurosecretion by residual axons, and denervation supersensitivity. The resulting tissue edema, hypoxia, and secondary central nervous system changes can exacerbate symptoms and perpetuate pathology. Restoring the interest of neurologists in RSD/CRPS should improve patient care and broaden our knowledge of small-fiber functions.