Prospective study of the additional benefit of plexus magnetic resonance imaging in the diagnosis of chronic inflammatory demyelinating polyneuropathy.

BACKGROUND AND PURPOSE: Hypertrophy/signal hyperintensity and/or gadolinium enhancement of plexus structures on magnetic resonance imaging (MRI) are observed in two-thirds of cases of typical chronic inflammatory demyelinating polyneuropathy (CIDP). The objective of our study was to determine the additional benefit of plexus MRI in patients referred to tertiary centers with baseline clinical and electrophysiological characteristics suggestive of typical or atypical CIDP. METHODS: A total of 28 consecutive patients with initial suspicion of CIDP were recruited in nine centers and followed for 2 years. Plexus MRI data from the initial assessment were reviewed centrally. Physicians blinded to the plexus MRI findings established the final diagnosis (CIDP or neuropathy of another cause). The proportion of patients with abnormal MRI was analyzed in each group. RESULTS: Chronic inflammatory demyelinating polyneuropathy was confirmed in 14 patients (50%), as were sensorimotor CIDP (n = 6), chronic immune sensory polyradiculoneuropathy (n = 2), motor CIDP (n = 1) and multifocal acquired demyelinating sensory and motor neuropathy (n = 5). A total of 37 plexus MRIs were performed (17 brachial, 19 lumbosacral and 8 in both localizations). MRI was abnormal in 5/37 patients (14%), all of whom were subsequently diagnosed with CIDP [5/14(36%)], after an atypical baseline presentation. With plexus MRI results masked, non-invasive procedures confirmed the diagnosis of CIDP in all but one patient [1/14 (7%)]. Knowledge of the abnormal MRI findings in the latter could have prevented nerve biopsy being performed. CONCLUSION: Systematic plexus MRI in patients with initially suspected CIDP provides little additional benefit in confirming the diagnosis of CIDP.

Upper limb onset of hereditary transthyretin amyloidosis is common in non-endemic areas.

BACKGROUND AND PURPOSE: The aim is to describe an uncommon phenotype of hereditary ATTR neuropathy with upper limb onset. METHODS: The French TTR Familial Amyloid Polyneuropathy database was used for a retrospective evaluation of 32 consecutive patients with upper limb onset of the neuropathy (study group) and they were compared to 31 Portuguese early-onset patients and 99 late-onset patients without upper limb onset. RESULTS: Initial upper limb symptoms were mostly sensory. Lower limb symptoms began 2.3 ± 3 years after upper limb symptoms. Twenty-four (75%) patients were initially misdiagnosed, with 15 different diagnoses. More patients in the study group had a Neuropathy Impairment Score upper limb/lower limb ratio > 1 compared to the late-onset patient group. The study group had significantly more pronounced axonal loss in the median and ulnar motor nerves and the ulnar sensory and sural nerves. On radial nerve biopsies (n = 11), epineurial vessels were abnormal in six cases, including amyloid deposits in vessel walls (3/11), with vessel occlusion in two cases. CONCLUSION: Upper limb onset of hereditary ATTR neuropathy is not rare in non-endemic areas. It is important to propose early TTR sequencing of patients with idiopathic upper limb neuropathies, as specific management and treatment are required.

High dose subcutaneous immunoglobulin for idiopathic inflammatory myopathies and dysimmune peripheral chronic neuropathies treatment: observational study of quality of life and tolerance.

BACKGROUND: In patients with autoimmune diseases who still derive benefit from high dose intravenous immunoglobulin (IVIg) treatment, some physicians resort to subcutaneous (SC) Ig as a replacement therapy. OBJECTIVE: To collect quality of life (QoL) and tolerance data on SCIg in patients for whom the switch from IVIg to SCIg is essential to maintain treatment. METHODS: This observational study included patients with either idiopathic inflammatory myopathies (IIM) or chronic dysimmune peripheral neuropathies (CDPN) treated with IVIg, who had been switched to SCIg administration for at least three months. The main objective was to describe the impact of SCIg on QoL after six months, using the generic Short-Form 36 questionnaire (SF-36). The secondary objectives were to evaluate SCIg tolerance and clinical efficiency. RESULTS: Eight centres recruited 12 IIM patients and two centres recruited 11 CDPN patients. Neither the physical nor the mental health SF-36 component summaries showed any QoL deterioration during the six-month study period and all IIM and CDPN patients remained clinically stable during the same period. The most frequent adverse effects were injection site reactions (50%), cutaneous tissue disorders (18.2%), and nervous system disorders (13.6%). Two serious adverse events (myocarditis and cerebrovascular accident) occurred in two patients. CONCLUSION: In these rare inflammatory diseases, high dose SCIg administration (which can be home based) has no deleterious effect on patient QoL. It appears to be a safe and efficient alternative to hospital-based IVIg.

[Atypical neuropathies associated with diabetes]. / Neuropathies atypiques du diabète.

Diabetes is the leading cause of neuropathy worldwide and, due to the epidemic progression of the affection, prevalence of diabetic neuropathies will increase in the near future. Beside the typical diabetic neuropathy pattern and the common entrapment neuropathies, several unusual clinical forms have been described with either a symmetrical or an asymmetrical pattern. Treatment-induced neuropathy is an acute sensory affection most commonly related to acute glycemic control. Pain is debilitating and associated with vegetative dysfunction. Prevention is important, as resolution is often incomplete. Several patterns or asymmetrical neuropathies of inflammatory and ischemic origin were described long ago in the lower limb. They are debilitating, most often painful and require steroid treatment. Other patterns affecting the thoracolumbar region or the upper limbs or involving a painless motor deficit must be identified as specific treatments are sometimes needed. An association between diabetes and chronic inflammatory demyelinating polyneuropathy has not been demonstrated but diagnosis may be suggested due to the misleading low conduction velocities seen in classical diabetic neuropathy. Like any other patient, the diabetic patient may present a neuropathy unrelated to diabetes. To facilitate patient care, neurologists should be aware of such clinical entities.

Reversibility of acquired amyloid polyneuropathy after liver retransplantation.

Domino liver transplantation (DLT) has become an accepted procedure designed to address problems with organ limited supply. However, cases of acquired amyloid neuropathy are increasingly being recognized following this procedure. Until now, only one patient had undergone liver retransplantation and follow-up findings were not reported. We describe the case of a 72-year-old patient with partial recovery from acquired amyloid neuropathy following retransplantation with a deceased donor 7 years after DLT performed for end-stage liver disease. His clinical and paraclinical improvement is described, and the impact of this case on the indication for a domino procedure and the challenges linked to retransplantation are discussed.

Effect on disability and safety of Tafamidis in late onset of Met30 transthyretin familial amyloid polyneuropathy.

BACKGROUND AND PURPOSE: The aim of this study was to assess the effect of Tafamidis, which slows the progression of early stages of Met30 transthyretin (TTR) familial amyloidosis polyneuropathy (FAP) in more advanced cases. METHODS: The study was a prospective, non-randomized controlled trial carried out at the French national reference centre for FAP with follow-up at 1 year. Thirty-seven consecutive Met30-TTR-FAP patients were enrolled between December 2009 and July 2011, with NIS-LL (Neuropathy Impairment Score-lower limbs) > 10 and Karnofsky score > 60. Their mean (SD) age was 56.4 (19) years. Seventy-seven per cent of patients had a walking disability. Seven patients (19%) were withdrawn for adverse effects. The primary study outcome measurements, planned before data collection began, were NIS-LL and NIS-UL (upper limbs) scores and disability scores. RESULTS: Of the 37 patients entered into the study, 29 were evaluated at 6 months and 13 at 12 months. During the first 6 months of treatment, the mean progression of NIS-LL score was 4.8 and was similar to that during the period before treatment. Among the 45% of patients without NIS-LL progression, the NIS-UL score worsened in 55%. During the first year, 55% deteriorated with respect to disability and 38% with respect to NIS only; only two patients (7%) remained stable. Four (out of 20; 20%) patients who were previously stage 1 reached stage 2 (walking with aid) after this period. Two out of nine patients who were initially normotensive developed orthostatic hypotension. There were a total of 19 adverse events, including four febrile urinary tract infections and three severe diarrhoeas, with faecal incontinence in two. CONCLUSION: In most patients with advanced Met30 TTR-FAP, Tafamidis is not able to stop disease progression, in respect of both NIS-LL and disability. Other anti-amyloid medicines should be assessed in this context.

Short and long-term effect of IVIg in demyelinating neuropathy associated with MGUS, experience of a monocentric study.

BACKGROUND: The optimal treatment for demyelinating neuropathy associated with MGUS and anti-MAG neuropathy is not known. METHODS: We retrospectively studied the efficacy of IVIg in 14 patients with DN-MGUS (seven IgM and seven IgG/A) and seven with anti-MAG neuropathies, treated in our reference center between 2002 and 2007. Patients were clinically evaluated before the first infusion, after the first infusion, and after the last IVIg treatment. RESULTS: Anti-MAG neuropathy: after a single infusion, one patient improved and six were stable. At last follow-up (mean: 15.6months [range: 3.5-31], mean number of IVIg courses: 8 [2-33]), one patient maintained her improvement from baseline. DN-MGUS: after a single infusion, nine patients improved (64%), four were stable and one deteriorated further. The factor predictive of short-term response to IVIg was relapsing neuropathy responding better in the walking score analysis (Fisher exact test: P=0.005). At last follow-up (mean: 22.6months [range 2-72], mean number of IVIg courses: seven [1-24]), neurological status improved in four patients, five patients remained stable, including three who are still under regular IVIg, and four had deteriorated. Improvement from baseline persisted for a prolonged period in two patients after IVIg were stopped. Patients who were responders on Norris after the first IVIg course were significantly better responders at long-term follow-up than the others (P=0.001). We report no serious adverse effect. CONCLUSION: IVIg are not very efficient in the management of anti-MAG neuropathies. Nevertheless, they have a frequent short-term beneficial effect in DN-MGUS, which was maintained at long-term follow-up in one-third of our patients. When a DN-MGUS patient is regularly treated by IVIg courses, frequent periodic clinical evaluations must be performed to determine when to stop treatment and switch to another one.

[New elements in the diagnosis and the treatment of primary AL amyloid polyneuropathy and neuropathy due to POEMS syndrome]. / Nouveautés dans le diagnostic et le traitement des neuropathies périphériques liées à l'amylose AL et au syndrome POEMS.

INTRODUCTION: Primary AL amyloid polyneuropathy (AL-PN) and neuropathy due to POEMS syndrome (POEMS-N) are rare, associated with a monoclonal gammopathy (MG) IgGλ or IgAλ at a low rate and systemic manifestations. They are invalidating and life-threatening. STATE OF THE ART: AL-PN usually mimics small fiber length-dependent axonal polyneuropathies, but also multifocal or painful neuropathies, POEMS-N corresponds to a rapid ascending CIDP with MG. To confirm the diagnosis of AL-PN, initial investigations should identify amyloidosis on nerve or accessory salivary glands, to establish the type of amyloid after serum free light-chain (FLC) measurements. For the diagnosis of N-POEMS, diagnosis is based on the presence of four criteria proposed by Dispenzieri. These neuropathies are associated with biomarkers, useful for diagnosis and treatment monitoring: elevated serum level of FLC monoclonal in (AL-PN) or VEGF (N-POEMS). PERSPECTIVES: Early diagnosis of these neuropathies and early treatment using high-dose melphalan associated with an autologous hematopoietic stem cell graft or low monthly doses can improve the clinical manifestations and patient survival. CONCLUSIONS: Systematic search for monoclonal gammopathy by immunofixation and serum free light chains is very useful for the management of progressive peripheral neuropathies of unknown origin.

Multifocal deficits due to leukemic meningoradiculitis in chronic lymphocytic leukemia.

Symptomatic nervous system leukemic infiltration is rarely observed in CLL. Various clinical manifestations including headache, confusion, cranial nerve palsies, focal central deficits and peripheral neuropathies have been seldom reported, occurring in less than 1% of patients. We report herein 2 CLL patients with unusual clinical presentations of nervous system invasion. They presented multiple progressive peripheral deficits due to meningoradiculitis. In both, CSF immunophenotyping analysis identified a majority of T cells (>90%), and less than 10% of B-CLL cells expressing CD5, CD19 and CD20. Our analyses revealed the transformation of CLL into an aggressive B-cell lymphoma in one case (Richter's syndrome). A post mortem study showed massive infiltration of cranial nerves and spinal roots by large B lymphomatous cells. In the other case, CNS oriented chemotherapy led to remission and total neurological recovery. In practice, the etiological diagnosis of neurological deficits in CLL patients is difficult. CSF analysis may be useful, requiring viral PCR, repeated cytological studies and immunophenotyping analysis. Although rare, leptomeningeal leukemic localization has to be discussed, even in the absence of overt Richter syndrome, and may require an early therapeutic test.

A brief compound test for assessment of autonomic and sensory-motor dysfunction in familial amyloid polyneuropathy.

BACKGROUND: Familial amyloid polyneuropathies (FAP) patients manifest progressive sensory-motor length dependent polyneuropathy and severe autonomic dysfunction. In this setting the autonomic manifestations include mainly postural hypotension, nausea and vomiting, diarrhea and constipation, sphincter distur- bances and erectile dysfunction. Reproducible quantitative evaluation of signs and symptoms are necessary for the assessment of treatment efficacy. OBJECTIVE: To determine the reliability of a new compound test cumulating evaluation of autonomic and sensorymotor dysfunction in FAP. METHODS: Compound Autonomic Dysfunction Test (CADT) is a new questionnaire to evaluate the main symptoms of autonomic dysfunction observed in FAP. A separate functional questionnaire assesses the disability due to the sensorymotor deficit (Modified Norris Test; MNT). The compound test takes approximately 10 minutes to perform. In this prospective study, we enrolled consecutively 60 FAP patients to test interexaminer reliability, i.e., both questionnaires rated independently by 2 examiners. We also evaluate the reliability of testing patients face to face and by phone call, by the same examiner. RESULTS: Interexaminer reliabilities tested were high (ICC=0.92 for the CADT, p < 0.001; and ICC = 0.99 for the MNT, p < 0.001). In addition, testing by phone as compared to testing during the initial medical visit by the same investigator gave similar results (ICC = 0.91 for the CADT, p < 0.001; and ICC = 0.98 for the MNT, p < 0.001). CONCLUSION: In FAP, the CADT and the MNT have good reliability inter-investigators as well as between face to face and by phone call, by the same examiner. This newly designed compound test is a simple and reproducible scale which is adapted to evaluate the main neuropathic manifestations and will be useful for assessment of future treatments in this condition.

Good prognosis of postpartum lower limb sensorimotor deficit: a combined clinical, electrophysiological, and radiological follow-up.

Postpartum lower limb motor and/or sensory deficit is an uncommon obstetrical complication. We aimed to identify its incidence, etiology, and precipitating factors, as well as the neurological prognosis by retrospectively analyzing the successive neurological evaluations, electrophysiological, and MRI data from all the consecutive patients with postpartum motor and/or sensory deficits of the lower limbs referred from the Lariboisière Obstetrical Department to the Lariboisière Neurophysiology Department, from January 2012 to June 2016, as well as data concerning labor and morphological characteristics of mother and baby. Thirteen patients (0.11% of the parturient women in the Lariboisière hospital) were included. Eight (62%) had lumbosacral plexopathy. Symptoms followed a first vaginal delivery in 10/13 patients (77%), in patients who were mostly overweight (mean patient BMI before pregnancy 25.6 ± 3.2 kg/m2). Labor duration was slightly longer than average (mean labor duration 8.9 ± 2.9 h). No other potentially precipitating factor was identified. Recovery was good in all patients, 7/11 (64%) made a rapid full recovery (mean recovery time 5 ± 2.5 weeks excluding one patient who had a normal neurological examination at 2 weeks but still complained of foot weakness that fully recovered in 1 year), and a minority (4/11, 36%) still complained of minor symptoms at time of follow-up, but showed marked improvement. New mothers presenting postpartum lower limb nerve injury should, therefore, be reassured.

Plasma exchanges for severe acute neurological deterioration in patients with IgM anti-myelin-associated glycoprotein (anti-MAG) neuropathy.

Monoclonal IgM anti-myelin-associated glycoprotein (MAG) antibody-related peripheral neuropathy (anti-MAG neuropathy) is predominantly a demyelinating sensory neuropathy with ataxia and distal paresthesia. The clinical course of anti-MAG neuropathy is usually slowly progressive making difficult the identification of clear criteria to start a specific treatment. Although no consensus treatment is yet available, a rituximab-based regimen targeting the B-cell clone producing the monoclonal IgM may be proposed, alone or in combination with alkylating agents or purine analogs. However, in some rare cases, an acute and severe neurological deterioration can occur in few days leading to a rapid loss of autonomy. In these cases, a treatment rapidly removing the monoclonal IgM from the circulation might be useful before initiating a specific therapy. We report successful treatment with plasma exchanges (PE) in four patients presenting with acute neurological deterioration. PE allowed a dramatic and rapid neurological improvement in all patients. PE are safe and may be useful at the initial management of these cases of anti-MAG neuropathy.

Axono-cortical evoked potentials: A proof-of-concept study.

Awake surgery is currently considered the best method to tailor intraparenchymatous resections according to functional boundaries. However, the exact mechanisms by which electrical stimulation disturbs behavior remain largely unknown. In this case report, we describe a new method to explore the propagation toward cortical sites of a brief pulse applied to an eloquent white matter pathway. We present a patient, operated on in awake condition for removal of a cavernoma of the left ventral premotor cortex. At the end of the resection, the application of 60Hz stimulation in the white matter of the operculum induced anomia. Stimulating the same site at a frequency of 1Hz during 70seconds allowed to record responses on electrodes put over Broca's area and around the inferior part of central sulcus. Axono-cortical evoked potentials were then obtained by averaging unitary responses, time-locked to the stimulus. We then discuss the origin of these evoked axono-cortical potentials and the likely pathway connecting the stimulation site to the recorded cortical sites.

[Management of neuropathic pain]. / Prise en charge de la douleur neuropathique.

Neuropathic pain is often underestimated and not adequately treated. The DN4 scale is very useful for its identification since it will benefit from pharmacological and non-pharmacological specific alternative care. The pathophysiological mechanisms involve the hyperexcitability of nociceptive pathways or decreased inhibitory descending controls that will be the target of pharmacological treatments. Frontline molecules are antidepressants (tricyclics and mixed serotonin and norepinephrine reuptake inhibitors) and antiepileptics (α2δ calcium channel inhibitors). However, these drugs will only have a partial efficacy on pain. The therapeutic strategy is based on reasonable goals, starting with a monotherapy adapted to the patient's symptoms and comorbidities and increased step by step. Patient compliance to contract is essential and requires clear and complete information. The impact on profession, social and family integration should rapidly be taken into account. In case of inefficiency, a change of the first-line treatment or an association could be considered. Some indications justify a specific therapy. Patients with resistant chronic pain should be sent to a specialized centre. New drugs are being studied and non-pharmacological support must be evaluated.

Somatosensory evoked potentials in the assessment of peripheral neuropathies: Commented results of a survey among French-speaking practitioners and recommendations for practice.

BACKGROUND: Somatosensory evoked potentials (SSEPs) are increasingly performed for the assessment of peripheral neuropathies, but no practical guidelines have yet been established in this specific application. STUDY AIM: To determine the relevant indication criteria and optimal technical parameters for SSEP recording in peripheral neuropathy investigation. METHODS: A survey was conducted among the French-speaking practitioners with experience of SSEP recording in the context of peripheral neuropathies. The results of the survey were analyzed and discussed to provide recommendations for practice. RESULTS: SSEPs appear to be a second-line test when electroneuromyographic investigation is not sufficiently conclusive, providing complementary and valuable information on central and proximal peripheral conduction in the somatosensory pathways. CONCLUSIONS: Guidelines for a standardized recording protocol, including the various parameters to be measured, are proposed. CLINICAL RELEVANCE: We hope that these proposals will help to recognize the value of this technique in peripheral neuropathy assessment in clinical practice.

[Perturbations of activities of daily living in Alzheimer's disease. A study of 172 patients with the using a questionnaire completed by caregivers]. / Perturbations des activités quotidiennes au cours de la maladie d'Alzheimer. Etude chez 172 patients à l'aide d'un questionnaire rempli par le conjoint.

Functional decline was studied retrospectively in 172 patients with Alzheimer's disease, AD, using a questionnaire completed by the caregiver. Ninety-nine of these patients had a second assessment after a follow-up of 22.1 +/- 13.8 months. The questionnaire included French versions of the Physical Self-Maintenance Activities, ADL, and of the Instrumental Activities of Daily Living, IADL (Lawton and Brody, 1969). A third part assessing social activities, SADL, was derived from Katz and Lyerly (1963). The earliest and most frequent perturbations in early AD involved SADL, mainly a reduction in social and leisure activities, appearing in subjects with a MMSE score > 26. The earliest decline in IADL involved the ability for handling finances, odd jobs-sewing, and shopping, which were more frequently perturbed than ability to use telephone, traveling or handling medication. The most interesting results of our study were as follows. Functional decline did not allow to distinguish patients with early AD (MMSE score > or = 24) from those with mild dementia (MMSE score 20-23). Mild perturbations of ADL, mainly dressing and walking, were observed in early AD. There was a good correlation, but no parallelism, between functional decline and cognitive decline. Disturbances in ADL and SADL significantly differed only between patients with severe dementia (MMSE < 10) and those of the three other groups. Apathy appeared to be a stronger predictor of functional decline than the score on the MMSE in the early stages of AD. There was a great variability among the patients regarding the type of functional decline as well as the rate of decline. Functional decline is very useful for detecting early AD. However, its specificity seems to be low and the diagnosis should be supported by cognitive assessment.

Advances in the treatment of chronic inflammatory demyelinating neuropathies in 2010.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon disease of the peripheral nerves. The diagnosis is based mainly on clinical presentation, cerebrospinal fluid (CSF) examination, and electrodiagnostic studies. Treatment of CIDP has at least two components: supportive care and specific therapy including primarily steroids, intravenous immunoglobulins (IVIg), and plasmapheresis (PE). This review summarizes progress in the treatment of CIDP published during the last year.

Multifocal neuropathy due to plasma cell infiltration of peripheral nerves in multiple myeloma.

Patients with multiple myeloma (MM) can manifest a variety of neurologic complications. The authors report two patients who had development of a multifocal neuropathy related to infiltration of peripheral nerves by malignant plasma cells as the only manifestation of a relapse of MM, which was considered in full remission.