Prevalence, correlates and impact of pain and cramps in anti-MAG neuropathy: a multicentre European study.

BACKGROUND AND PURPOSE: The frequency of pain and cramps is uncertain in anti-myelin associated glycoprotein antibody (anti-MAG) neuropathy. Whether these symptoms may affect function/quality of life is unknown. METHODS: A cross-sectional study of the prevalence, correlates and impact of pain, pain subtypes and cramps, their severity, frequency and anatomical distribution was performed for 55 clinically stable patients with anti-MAG neuropathy. RESULTS: Pain of any type was reported by 80% of subjects. The most common subtype was paraesthesiae and dysaesthesiae (70%). Cramps were reported by >60% of patients, with lower limb cramps in all and upper limb cramps in about 20%. Cramps affected daily activities in >30% of these subjects, sleep in 60%, ability to exercise in >30%. Total pain score correlated with several Short Form 36 health-related quality of life (SF-36 HR-QoL) measures (P < 0.05), with Inflammatory Rasch-built Overall Disability Scale (I-RODS) (P = 0.006) and 10-m timed walk (P = 0.019). An independent association was ascertained with I-RODS (P = 0.002). Different pain subtypes showed multiple associations with SF-36 HR-QoL measures and/or functional scales. Upper limb cramps had multiple SF-36 HR-QoL functional correlates, with an independent association with the Overall Neuropathy Limitation Score (ONLS) (P = 0.004). Cramp severity correlated with ONLS (P = 0.04) and I-RODS (P = 0.028) and inversely with level of physiotherapy input (P = 0.009). Cramp frequency was associated with tremor score (P = 0.004) and multiple SF-36 HR-QoL subsections. CONCLUSIONS: Neuropathic pain and cramps may affect function and quality of life in anti-MAG neuropathy. Optimizing treatments of these symptoms, including by adequate levels of physiotherapy, may be beneficial in affected patients and requires further research.

Serial electrophysiology in Guillain-Barré syndrome: A retrospective cohort and case-by-case multicentre analysis.

OBJECTIVES: To assess the usefulness of serial electrophysiology in Guillain-Barré syndrome (GBS) in a multicenter setting and the reasons for change in electrodiagnostic subtypes with serial studies. METHODS: We retrospectively analysed serial electrophysiology of 51 patients with GBS from 4 European centres. Proportions of subtypes were determined at each timing. Individual case analyses were also performed where diagnostic changes occurred with either criteria, to ascertain if changes were due to disease progression or criteria inadequacy. RESULTS: At first study, comparing old vs new criteria, acute inflammatory demyelinating polyneuropathy (AIDP) was diagnosed in 70.6% vs 51%, axonal GBS in 15.7% vs 39.2%, equivocal forms in 11.8% vs 7.8%. At second study, AIDP was diagnosed in 72.5% vs 52.9%, axonal GBS in 9.8% vs 33.3%, equivocal forms in 15.7% vs 11.7%. Subtype proportions were unchanged, indicating serial studies did not, in the cohort, alter diagnostic rates for each subtype irrespective of criteria used. Individual review of cases where subtype electrodiagnosis changed indicated suboptimal specificity for AIDP/sensitivity for axonal GBS as main cause of diagnostic shifts with old criteria, whereas disease progression explained most changes with new criteria (55.6% vs 81.8%; P = .039). CONCLUSIONS: Serial electrophysiology is unhelpful in GBS. Repeat studies cannot represent the gold standard as electrodiagnosis may alter due to disease progression. Changes in electrodiagnosis relate more often to disease progression with new criteria but are more frequently due to suboptimal sensitivity/specificity with old criteria. A single electrophysiological study using the most accurate available criteria appears sufficient in GBS.

Newer anti-epileptic drugs, vitamin status and neuropathy: A cross-sectional analysis.

OBJECTIVE: Whether new antiepileptic drugs (AEDs) may result in neuropathy is unknown but possible given their effects on vitamin metabolism. This analysis aimed to determine frequency and correlates of neuropathy in subjects treated with new AEDs in relation to drug used, length of exposure and serum vitamin B12 and folate levels. METHODS: We performed a cross-sectional study of 52 consecutive epileptic subjects. Presence of neuropathy was determined using the Utah Early Neuropathy Score (UENS). Exposure to anti-epileptic drugs was quantified. Serum vitamin B12 and folate levels were measured. RESULTS: Commonly used AEDs were levetiracetam (28/52), carbamazepine (20/52), lamotrigine (20/52), sodium valproate (10/52) and zonisamide (10/52). Eight of 52 (15.4%) patients had neuropathy. There was no association with any particular AED. Neuropathy correlated with age (P=0.038) and total exposure to AEDs (P=0.032). UENS correlated with age (P=0.001), total AED exposure (P=0.001) and serum vitamin B12<240ng/L (P=0.018). Independent association of neuropathy was found with total AED exposure (P=0.032), but not age. UENS was independently associated with total exposure to AEDs (P<0.001), vitamin B12<240ng/L (P=0.002), but not age. Serum vitamin B12 and folate levels were highly inter-correlated (P<0.001). CONCLUSIONS: Neuropathy appears to be associated with the length of exposure to new AEDs. This may relate to the effects of new AEDs on vitamin B12 and folate metabolism. Although further research from controlled studies is needed and despite the presence of other possible confounding factors, monitoring for neuropathy and vitamin B12 and folate levels merits consideration in patients on long-term treatment with new AEDs.

Steroids for chronic inflammatory demyelinating polyradiculoneuropathy: evidence base and clinical practice.

Evidence-based therapies for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) consist of corticosteroids, intravenous immunglobulins (IVIg), and plasma exchange. Steroids represent the oldest treatment used historically. In countries where readily available and affordable, IVIg tends to be favored as first-line treatment. The reason for this preference, despite substantially higher costs, is the perception that IVIg is more efficacious and safer than corticosteroids. However, the unselected use of IVIg as a first-line treatment option in all cases of CIDP raises issues of cost-effectiveness in the long-term. Furthermore, serious although rare, particularly thromboembolic side effects may result from their use. Recent data from randomized trials suggest pulsed corticosteroids to have a higher potential in achieving therapy-free remission or longer remission-free periods compared with IVIg, as well as relatively low rates of serious side effects when given as pulsed intravenous infusions during short periods of time. These specific advantages suggest that pulsed steroids could in many cases be used, as the first, rather than second choice of treatment when initiating immunomodulation in CIDP, primarily in hopes of achieving a remission after the short-term use. This article reviews the evidence base for the use of corticosteroids in its various forms in CIDP and factors that may influence clinicians' choice between IVIg and pulsed steroid treatment. The issue of efficacy, relapse rate and time, and side effect profile are analyzed, and some aspects from the authors' experience are discussed in relation to the possibility of using the steroid option as first-line therapy in a large proportion of patients with CIDP.

Hyponatraemia in Guillain-Barré syndrome revisited.

OBJECTIVES: The objective of this study was to determine the relevance of hyponatraemia in the prognosis of Guillain-Barré syndrome (GBS). MATERIALS AND METHODS: We retrospectively analysed records of 48 consecutive patients with GBS and performed a systematic literature review on frequency/correlates of hyponatraemia in GBS. RESULTS: Hyponatraemia <133 mmol/l was detected in 18/48 of our patients with GBS (37.5%). In 10/18 (55.5%), hyponatraemia occurred post-immunoglobulin therapy. Hyponatraemia correlated with age >50 years (P = 0.011), concurrent malignancy (P = 0.039), diuretic use (P < 0.001), preceding diarrhoea (P = 0.042) and Medical Research Council (MRC) sum score at discharge (MRCSSD) (P = 0.026). Only concurrent malignancy (P < 0.001) and diuretic use (P < 0.001) were independently associated with hyponatraemia. MRCSSD also correlated with MRC sum score on admission (MRCSSA) (P < 0.001), length of hospital stay (P < 0.001), summated compound muscle action potential (P = 0.034) and lowest forced vital capacity (P = 0.001). Only MRCSSA (P = 0.004) and length of hospital stay (P < 0.001) independently predicted MRCSSD. Combining our findings with previous literature indicates comparable frequencies of hyponatraemia in GBS in four of five studies and association with mortality in three of four studies, with an independent link in one. Independent association of hyponatraemia with muscle strength is not demonstrated. CONCLUSION: Hyponatraemia appears of comparable frequency in GBS to that in other diseased cohorts suggesting it is common but non-specific. Hyponatraemia has otherwise been shown to be an independent predictor of death in other disorders and available data indicate the same is also likely in GBS, although this may vary in patient subgroups. Hyponatraemia is, however, not an independent prognostic indicator of neuromuscular weakness severity in GBS.

Disease status in chronic inflammatory demyelinating polyneuropathy: inter-centre comparative analysis and correlates.

BACKGROUND AND PURPOSE: Chronic inflammatory demyelinating polyneuropathy (CIDP) may have variable evolution profiles, which have not been compared between cohorts. The relationship of disease status with motor strength, function and electrophysiology is uncertain. METHODS: Disease status was studied with a simplified proposed scale in two patient cohorts totalling 72 subjects from Leicester, U.K., and Angers, France. Clinical and electrophysiological records were analysed. RESULTS: Independent ascertainment of disease status in each cohort revealed similar rates of remission (P = 0.23), stable/improving disease (P = 0.34) and unstable/active disease (P = 1). No correlation was ascertained with strength or function. Median nerve compound muscle action potential was the only independent electrophysiological predictor of disease status ascertained (P = 0.046). CONCLUSIONS: Disease status distribution may represent an important comparative indicator for management of CIDP cohorts and could be useful for benchmarking service and treatment provision. Degree of upper limb motor axonal loss may represent a useful electrophysiological marker of disease status in CIDP.

Optic and auditory pathway dysfunction in demyelinating neuropathies.

OBJECTIVE: The involvement of optic and auditory pathways has rarely been studied in demyelinating polyneuropathies. We here aimed to study this further in a cohort of patients with acquired and gentic demyelinating neuropathy. METHODS: We studied eight patients with hereditary neuropathy with liability to pressure palsies (HNPP), six with Charcot-Marie-Tooth disease type 1A (CMT1A), ten with chronic inflammatory demyelinating polyneuropathy (CIDP) and seven with antimyelin-associated glycoprotein (MAG) neuropathy using visual evoked potentials and brainstem auditory evoked potentials. RESULTS: Optic pathway dysfunction was detected in 6/7 anti-MAG neuropathy patients, about half of those with CIDP and HNPP, but only in 1/6 patients with CMT1A. Peripheral auditory nerve dysfunction appeared common in all groups except HNPP. Brainstem involvement was exceptional in all groups. CONCLUSIONS: We conclude optic nerve involvement may be frequent in all demyelinating polyneuropathies, particularly anti-MAG neuropathy, except in CMT1A. Peripheral auditory nerves may be spared in HNPP possibly due to absence of local compression. Evidence for central brainstem pathology appeared infrequent in all four studied neuropathies. This study suggests that acquired and genetic demyelinating polyneuropathies may be associated with optic and auditory nerve involvement, which may contribute to neurological disability, and require greater awareness.

No association between neuropathy and restless legs in Parkinson's disease.

BACKGROUND: The prevalence of restless legs syndrome (RLS) has been studied extensively in Parkinson's disease (PD), with conflicting findings. More recently, both neuropathy and leg motor restlessness (LMR) have been found to be significantly more prevalent in PD patients than in controls. AIMS: Our objective was to determine whether RLS or LMR may be secondary to neuropathy, or its currently postulated determinants, cumulative levodopa usage and vitamin B(12) metabolism, in patients with PD. MATERIALS AND METHODS: We compared prevalence of RLS, LMR and neuropathy in 37 PD patients and 37 age- and gender-matched controls. Correlations between RLS/LMR and neuropathy and symptomatic neuropathy, cumulative levodopa usage and vitamin B(12) levels were ascertained. RESULTS: RLS prevalence was comparable in PD patients and controls (16.2% vs 10.8%; P = 0.30). LMR was significantly more common in PD patients than in controls (40.5% vs 16.2%; P = 0.038), as was neuropathy (37.8% vs 8.1%; P = 0.005). Neither RLS, nor LMR correlated with neuropathy or symptomatic neuropathy, cumulative levodopa exposure or serum vitamin B(12) levels in patients with PD. There was a non-significant trend for a correlation between LMR and earlier age of onset of PD (P = 0.069). CONCLUSIONS: RLS and LMR appear unrelated to neuropathy or symptomatic neuropathy, cumulative levodopa usage, or serum vitamin B(12) levels in patients with PD. The occurrence of LMR may relate to the earlier onset of PD, raising the possibility of common pathophysiological mechanisms for PD and RLS, of which LMR may be an early manifestation in some patients.

Restless legs syndrome in sensory axonal neuropathy: A case-control study.

INTRODUCTION: The relation between neuropathy and restless legs syndrome (RLS) remains uncertain. Previous studies have analyzed heterogeneous neuropathic populations and findings have been to date inconsistent. MATERIALS AND METHODS: We studied a neuropathic population consisting of 59 patients with acquired, mixed, small and large fiber sensory axonal neuropathy. We compared our findings to those of 59 neurological controls with a similar age/gender distribution. International RLS Study Group criteria were used and severity assessed by International Restless Legs Syndrome Severity Scores (IRLSSS), by a single blinded telephone interviewer. Mimics were excluded as well as cases with infrequent (<5 days/month) symptoms. RESULTS: RLS was significantly more frequent in patients with neuropathy than in controls (28.8% versus 8.5%; P=0.008). Patients with neuropathy and RLS were significantly older (P=0.001), had later onset RLS (P=0.001), had more frequent RLS symptoms (P=0.009) and greater IRLSSS (P=0.019), than controls with RLS. There was no relation between presence of RLS in patients with sensory neuropathy and lower limb sensory electrophysiological findings. CONCLUSIONS: Our results suggest that acquired sensory axonal neuropathy may be associated with RLS. Further larger studies of homogeneous neuropathic populations are required in view of the potential therapeutic benefit specifically for RLS symptoms in patients with neuropathy.

A European multicentre reappraisal of distal compound muscle action potential duration in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: The electrodiagnostic value of distal compound muscle action potential duration (DCMAPD) has been studied rarely in chronic inflammatory demyelinating polyneuropathy (CIDP). Cut-offs proposed have not been widely evaluated. The influence of low-cut EMG filter settings ≤ 10 Hz as used in Europe is uncertain. METHODS: We retrospectively reviewed records of 110 patients with typical, treatment-responsive CIDP, from Leicester, U.K., Paris and Angers, France. All fulfilled revised European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) clinical and electrodiagnostic criteria for typical CIDP (2010), before consideration of DCMAPD prolongation. Results were compared with those of 110 controls with chronic sensory/sensory-motor axonal neuropathy. We constructed receiver operating characteristic (ROC) curves for each nerve and derived cut-offs for DCMAPD prolongation, offering specificity of ≥ 98% vs. controls. RESULTS: DCMAPD was significantly greater in all nerves for CIDP patients, compared with controls (P < 0.001). ROC curves allowed derivation of cut-offs of sensitivities ranging from 27.1% (ulnar nerve) to 60% (tibial nerve). Using these cut-offs to define DCMAPD prolongation in any studied motor nerve offered a sensitivity of 69.1% for CIDP and specificity of 97.3% vs. controls. CONCLUSION: Cut-offs for DCMAPD are dependent on EMG filter settings. DCMAPD prolongation in any motor nerve, using our derived cut-offs, represents a sensitive and specific marker of CIDP in patients studied with EMG equipment with low-cut filter settings ≤ 10 Hz. Appropriate use of this parameter appears an essential criterion to consider in assessing suspected CIDP, which may be helpful in limiting extensiveness and duration of electrophysiological testing, thereby reducing patient discomfort.

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.

Neuropathy and paraproteins: review of a complex association.

Coexistence of neuropathy and monoclonal gammopathy represents a common but complex problem in clinical practice. This association is here reviewed considering latest available literature. The association is not infrequent, and various possible syndromes need to be distinguished. However, coincidental co-occurrence also needs to be recognized. The monoclonal gammopathy may be a 'monoclonal gammopathy of uncertain significance' (MGUS) or occur in a context of malignancy such as multiple myeloma or Waldenström's macroglobulinaemia. IgM paraproteins can bind to myelin-associated glycoprotein (MAG) in peripheral nerve. In this case, the paraprotein is directly linked to the neuropathy, causing a specific phenotype. One randomized controlled trial of this ('Anti-MAG') neuropathy showed possible moderate effect of rituximab on disability. Results of another trial are awaited. IgM/G/A paraproteins can be associated with a polyneuropathy indistinguishable from chronic inflammatory demyelinating polyneuropathy. Axonal neuropathies may coexist with IgM/G/A MGUS. There is insufficient evidence about causality or effective treatment in such cases. Pain/dysautonomia with an axonal neuropathy and serum paraprotein raises the possibility of amyloidosis. Specific haematological treatment is required for malignant disorders, although caution is required with neurotoxic agents. Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome and chronic ataxic neuropathy with ophthalmoplegia, M-protein, cold agglutinins and disialosyl antibodies represent rare separate entities for which evidence-based treatment options are still lacking. The association of monoclonal gammopathy and neuropathy requires the appropriate neurological/haematological investigations for a precise diagnosis. Causality is only established in few cases. Adequate management ideally requires joint neurological/haematological input for diagnosis, monitoring and treatment.

Distribution, clinical correlates and significance of axonal loss and demyelination in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: The distribution of axonal loss and demyelination has rarely been studied in chronic inflammatory demyelinating polyneuropathy (CIDP). Whether electrophysiological parameters may represent clinically relevant biomarkers of disease activity in the disorder remains uncertain. The purpose of this study was (i) to ascertain the distribution of electrophysiological motor abnormalities to optimize the diagnostic utility of nerve conduction studies and (ii) to establish electro-clinical correlations in an attempt to find the potential parameters that could represent adequate biomarkers of disease activity and prognosis. METHODS: The clinical and electrophysiological motor features of 31 prospectively recruited patients with clinically stabilized CIDP were analysed. RESULTS: Axonal loss predominated in the lower limbs, but demyelination was more common in the upper limbs. About 50% of all demyelinating abnormalities were detected in asymptomatic regions. Presence of weakness correlated with abnormal compound muscle action potential (CMAP) and abnormal motor nerve conduction velocity (MNCV). Degree of weakness and functional scores only consistently correlated with CMAP amplitudes. CMAP abnormality correlated with abnormal MNCV, abnormal distal motor latency (DML) and presence of conduction block (CB). However, although CMAP amplitudes also correlated with MNCVs and DMLs in raw values, they did not relate to the degree of CB. CONCLUSION: Electrodiagnosis of CIDP is optimized by extensive testing of upper limb nerves and of asymptomatic regions. Raw value CMAP amelioration and MNCV normalization may be adequate markers of clinical improvement in CIDP. Similarly, raw value MNCV and DML amelioration, as well as CB reversal may represent adequate prognostic markers.

Neuropathy and impaired glucose tolerance: an updated review of the evidence.

There has been considerable interest in the possible association between impaired glucose tolerance (IGT) and neuropathy. A systematic literature search (Medline) and review was here performed. Twenty-three studies were evaluated. Fourteen investigated for the presence of neuropathy in patients with IGT. Nine studied patients with chronic idiopathic axonal polyneuropathy (CIAP), for the prevalence of IGT. The findings suggest that a significant proportion of patients with IGT may have neuropathy, particularly of the small-fibre and painful type. Similarly, a significant percentage of patients without another identifiable cause for painful axonal neuropathy may have IGT. This may however not be applicable to all populations. There are issues relating to the reproducibility, reliability and timing of a single glucose tolerance test (GTT) in establishing a diagnosis of IGT. Furthermore, it is possible neuropathic damage may occur at lower glucose levels than those defining IGT. In conclusion, further prospective long-term study of large IGT cohorts with known prestudy IGT duration is required to confirm and answer the many remaining questions about this presumed association. However, at present time, consideration of IGT as potential cause of painful small-fibre neuropathy appears justified, especially as patients may benefit from dietary and physical exercise interventions.

Intravenous immunoglobulin and intravenous methylprednisolone as optimal induction treatment in chronic inflammatory demyelinating polyradiculoneuropathy: protocol of an international, randomised, double-blind, placebo-controlled trial (OPTIC).

BACKGROUND: International guidelines recommend either intravenous immunoglobulin (IVIg) or corticosteroids as first-line treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). IVIg treatment usually leads to rapid improvement and is generally safe, but does not seem to lead to long-term remissions. Corticosteroids act more slowly and are associated with more side effects, but may induce long-term remissions. The hypothesis of this study is that combined IVIg and corticosteroid induction treatment will lead to more frequent long-term remissions than IVIg treatment alone. METHODS: An international, randomised, double-blind, placebo-controlled trial, in adults with 'probable' or 'definite' CIDP according to the EFNS/PNS 2010 criteria. Three groups of patients are included: (1) treatment naïve, (2) known CIDP patients with a relapse after > 1 year without treatment, and (3) patients with CIDP who improved within 3 months after a single course of IVIg, who subsequently deteriorate at any interval without having received additional treatment. Patients are randomised to receive 7 courses of IVIg and 1000 mg intravenous methylprednisolone (IVMP) (in sodium chloride 0.9%) or IVIg and placebo (sodium chloride 0.9%), every 3 weeks for 18 weeks. IVIg treatment consists of a loading dose of 2 g/kg (over 3-5 days) followed by 6 courses of IVIg 1/g/kg (over 1-2 days). The primary outcome is remission at 1 year, defined as improvement in disability from baseline, sustained between week 18 and week 52 without further treatment. Secondary outcomes include changes in disability, impairment, pain, fatigue, quality of life, care use and costs and (long-term) safety. DISCUSSION: In case of superiority of the combined treatment, patients will experience the advantages of two proven efficacious treatments, namely rapid improvement due to IVIg and long-term remission due to corticosteroids. Long-term remission would reduce the need for maintenance IVIg treatment and may decrease health care costs. Additionally, we expect that the combined treatment leads to a higher proportion of patients with improvement as some patients who do not respond to IVIg will respond to corticosteroids. Risks of short and long-term additional adverse events of the combined treatment need to be assessed. TRIAL REGISTRATION: ISRCTN registry ISRCTN15893334 . Prospectively registered on 12 February 2018.

Electrophysiological sensory demyelination in typical chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: The presence of electrophysiological demyelination of sensory nerves is not routinely assessed in the evaluation of suspected chronic inflammatory demyelinating polyneuropathy (CIDP). Whether this can be useful is unknown. METHODS: We compared, using surface recording techniques, in 19 patients with typical CIDP and 26 controls with distal large fibre sensory axonal neuropathy, the forearm median sensory conductions, sensory nerve action potential (SNAP) amplitudes and durations and sensory nerve conduction velocities (SNCVs) of median, radial and sural nerves. RESULTS: Median nerve sensory conduction block (SCB) across the forearm was greater in CIDP patients than in controls (P = 0.005). SNAP durations were longer in CIDP patients for median (P = 0.001) and sural nerves (P = 0.004). Receiver operating characteristic (ROC) curves provided sensitive (>40%) and specific (>95%) cut-offs for median nerve SCB as well as median and sural SNAP durations. SNCVs were significantly slower for median and sural nerves in CIDP patients, but ROC curves did not demonstrate cut-offs with useful sensitivities/specificities. Median SCB or prolonged median SNAP duration or prolonged sural SNAP duration offered a sensitivity of 73.7% for CIDP and specificity of 96.2%. Used as additional parameters, they improved diagnostic sensitivity of the American Academy of Neurology (AAN) criteria for CIDP of 1991, from 42.1% to 78.9% in this population, with preserved specificity of 100%. DISCUSSION: Sensory electrophysiological demyelination is present and may be diagnostically useful in typical CIDP. SCB detection and SNAP duration prolongation appear to represent more useful markers of demyelination than SNCV reduction.

Validity of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy: a multicentre European study.

BACKGROUND: Diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) have variable sensitivity and specificity. Newly published criteria by Koski et al combine clinical and electrophysiological components, either of which suffices to establish the diagnosis. European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria require mandatory electrophysiology, as do other sets of criteria. METHODS: The value of the two above-mentioned sets of criteria, on 151 patients with CIDP, and 162 controls with axonal neuropathy, from four European centres was assessed. Results were compared with Van den Bergh and Piéret's criteria and those of the American Academy of Neurology (AAN). The utility of more extensive nerve-conduction studies was ascertained. RESULTS: Koski et al's criteria had a sensitivity of 63% and specificity of 99.3%. With unilateral, right-sided, forearm/foreleg, four-nerve studies, EFNS/PNS criteria offered a sensitivity of 81.3% and specificity of 96.2% for "definite/probable" CIDP. Van den Bergh and Piéret's criteria had a sensitivity of 79.5% and specificity of 96.9%. AAN criteria were poorly sensitive (45.7%) but highly specific (100%). "Possible" electrophysiological CIDP as per EFNS/PNS criteria were poorly specific (69.2%). More extensive studies increased the diagnostic sensitivity of EFNS/PNS criteria (96.7%) but reduced the specificity (79.3%). CONCLUSIONS: In our patient populations, the EFNS/PNS criteria were the most sensitive and allowed identification of a highly significantly greater number of patients than Koski et al's criteria. The latter were comparable in specificity with the "definite/probable" EFNS/PNS electrodiagnostic subcategories. More extensive nerve-conduction studies improved diagnostic yield but resulted in loss of specificity.

Electrophysiological markers of large fibre sensory neuropathy: a study of sensory and motor conduction parameters.

BACKGROUND: The frequency of sural sensory nerve action potential (SNAP) abnormalities in large fibre sensory neuropathy (LFSN) is uncertain. When sural SNAPs are normal, the sural/radial amplitude ratio (SRAR) was found to improve diagnostic yield in some studies. Motor parameters have been studied rarely, but may be helpful in this setting. METHODS: The electrophysiology of 105 consecutive patients with LFSN was reviewed and compared with that of 62 controls. We determined (i) the frequency of abnormal sural SNAPs, (ii) the proportion of patients with normal sural SNAPs but reduced SRAR <0.21 and (iii) the utility of motor studies (motor nerve conduction velocity, compound muscle action potential, F-wave). RESULTS: Reduced age-adjusted sural SNAPs were present in 54.3% of all patients. In those with normal age-adjusted sural SNAPs, SRAR <0.21 offered a sensitivity of 52.1% and specificity of 83.9%, and prolonged lower limb F-wave latency >105% of the upper limit of normal (ULN) offered a sensitivity of 29.2% and specificity of 90%. Independently and in combination, both parameters significantly improved diagnostic yield. DISCUSSION: The combined use of SRAR <0.21 and/or lower limb F-wave delay >105% of the ULN may be useful in patients with LFSN and normal sural SNAPs.

Hypothermia in VGKC antibody-associated limbic encephalitis.

Voltage-gated potassium channel antibody (VGKC-Ab)-associated limbic encephalitis (LE) is a recently described syndrome that broadens the spectrum of immunotherapy-responsive central nervous system disorders. Limbic encephalitis is typically characterised by a sub-acute onset of disorientation, amnesia and seizures, but the clinical spectrum is not yet fully defined and the syndrome could be under-diagnosed. We here describe the clinical profile of four patients with VGKC-Ab-associated LE who had intermittent, episodic hypothermia. One of the patients also described a prodrome of severe neuropathic pain preceding the development of limbic symptoms. Both of these novel symptoms responded well to immunosuppressive therapy, with concurrent amelioration of amnesia/seizures.