François Ochsner

Efficacy of lidocaine patch 5% in the treatment of focal peripheral neuropathic pain syndromes: a randomized, double-blind, placebo-controlled study

&NA; Peripheral neuropathic pain syndromes (PNPS) are difficult to treat because commonly used analgesics are often ineffective when, for example, touch‐evoked allodynia, hyperalgesia, and pain paroxysms are present. To investigate whether lidocaine patch 5% treatment is also effective in postherpetic neuropathy (PHN) and in other PNPS, 40 patients with various forms and localizations of PNPS completed a prospective, randomized, placebo‐controlled, two‐way, cross‐over study in three medical hospitals. Patients suffering from pain in a localized skin area with intensity above 40 mm visual analog scale (VAS) and a stable consumption of pain medication were included in this study. The study was divided into four phases: 3‐day run‐in phase, treatment phase 1, wash‐out period, and treatment phase 2, each lasting 1 week. At the discretion of the patients, up to four patches (covering a maximum of 560 cm2) were applied onto the maximally painful area for 12 consecutive hours daily, always either by day or at night. Throughout the four phases, ongoing pain, allodynia, quality of neuropathic symptoms, quality of sleep, and adverse events were assessed. When, after the wash‐out period, the pain intensity scores did not return to the pre‐treatment values (±20%), these patients were excluded from the study. The present study revealed that, as an add‐on therapy, the lidocaine patch 5% was clearly effective in reducing ongoing pain (P=0.017) and allodynia (P=0.023) during the first 8 h after application and that the patches also worked well over a period of 7 days (P=0.018) in diverse focal PNPS. Calculation of the numbers needed to treat (NNT) to obtain one patient with more than 50% relief of ongoing pain revealed that the NNT of 4.4 in the present study compared reasonably well with other studies of PHN, such as topically applied capsaicin (NNT: 5.3–∞) or systemic treatment with gabapentin (NNT: 3.2–5.0).

Amyotrophie de type Charcot-Marie-Tooth associée à une ataxie cérébelleuse autosomique récessive révélatrice d’une mutation du gène de l’aprataxine

ResumeIntroduction Le demembrement des ataxies cerebelleuses autosomiques recessives (ARCA) est actuellement possible par une correlation phenotype-genotype. L’orientation initiale est fonction des signes associes a l’ataxie. Observations Deux freres ont developpe une ataxie cerebelleuse avec une polyneuropathie amyotrophiante severe evoquant une neuropathie de type Charcot-Marie-Tooth, les confinant des l’adolescence au fauteuil roulant. L’examen a aussi mis en evidence une apraxie oculaire. La biopsie surale demontra une deperdition des fibres nerveuses de tous calibres, a l’exception des fibres non myelinisees, et le bilan biologique une hypercholesterolemie avec une hypoalbuminemie. L’analyse moleculaire a permis d’identifier une mutation homozygote W279X du gene APTX, responsable de l’ataxie avec apraxie oculomotrice de type 1 (AOA1). Conclusions Ces observations permettent de discuter du phenotype AOA1 et du diagnostic differentiel des ARCA, base sur la presence ou non d’une neuropathie peripherique, dont les causes restent a determiner.

Clinical, Biomarker, and Molecular Delineations and Genotype-Phenotype Correlations of Ataxia With Oculomotor Apraxia Type 1

Importance Ataxia with oculomotor apraxia type 1 (AOA1) is an autosomal recessive cerebellar ataxia due to mutations in the aprataxin gene (APTX) that is characterized by early-onset cerebellar ataxia, oculomotor apraxia, axonal motor neuropathy, and eventual decrease of albumin serum levels. Objectives To improve the clinical, biomarker, and molecular delineation of AOA1 and provide genotype-phenotype correlations. Design, Setting, and Participants This retrospective analysis included the clinical, biological (especially regarding biomarkers of the disease), electrophysiologic, imaging, and molecular data of all patients consecutively diagnosed with AOA1 in a single genetics laboratory from January 1, 2002, through December 31, 2014. Data were analyzed from January 1, 2015, through January 31, 2016. Main Outcomes and Measures The clinical, biological, and molecular spectrum of AOA1 and genotype-phenotype correlations. Results The diagnosis of AOA1 was confirmed in 80 patients (46 men [58%] and 34 women [42%]; mean [SD] age at onset, 7.7 [7.4] years) from 51 families, including 57 new (with 8 new mutations) and 23 previously described patients. Elevated levels of &agr;-fetoprotein (AFP) were found in 33 patients (41%); hypoalbuminemia, in 50 (63%). Median AFP level was higher in patients with AOA1 (6.0 ng/mL; range, 1.1-17.0 ng/mL) than in patients without ataxia (3.4 ng/mL; range, 0.8-17.2 ng/mL; P < .01). Decreased albumin levels (&rgr; = −0.532) and elevated AFP levels (&rgr; = 0.637) were correlated with disease duration. The p.Trp279* mutation, initially reported as restricted to the Portuguese founder haplotype, was discovered in 53 patients with AOA1 (66%) with broad white racial origins. Oculomotor apraxia was found in 49 patients (61%); polyneuropathy, in 74 (93%); and cerebellar atrophy, in 78 (98%). Oculomotor apraxia correlated with the severity of ataxia and mutation type, being more frequent with deletion or truncating mutations (83%) than with presence of at least 1 missense variant (17%; P < .01). Mean (SD) age at onset was higher for patients with at least 1 missense mutation (17.7 [11.4] vs 5.2 [2.6] years; P < .001). Conclusions and Relevance The AFP level, slightly elevated in a substantial fraction of patients, may constitute a new biomarker for AOA1. Oculomotor apraxia may be an optional finding in AOA1 and correlates with more severe disease. The p.Trp279* mutation is the most frequent APTX mutation in the white population. APTX missense mutations may be associated with a milder phenotype.

Acute painful diabetic neuropathy: an uncommon, remittent type of acute distal small fibre neuropathy

INTRODUCTION Acute painful diabetic neuropathy (APDN) is a distinctive diabetic polyneuropathy and consists of two subtypes: treatment-induced neuropathy (TIN) and diabetic neuropathic cachexia (DNC). The characteristics of APDN are (1.) the small-fibre involvement, (2.) occurrence paradoxically after short-term achievement of good glycaemia control, (3.) intense pain sensation and (4.) eventual recovery. In the face of current recommendations to achieve quickly glycaemic targets, it appears necessary to recognise and understand this neuropathy. METHODS AND RESULTS Over 2009 to 2012, we reported four cases of APDN. Four patients (three males and one female) were identified and had a mean age at onset of TIN of 47.7 years (±6.99 years). Mean baseline HbA1c was 14.2% (±1.42) and 7.0% (±3.60) after treatment. Mean estimated time to correct HbA1c was 4.5 months (±3.82 months). Three patients presented with a mean time to symptom resolution of 12.7 months (±1.15 months). One patient had an initial normal electroneuromyogram (ENMG) despite the presence of neuropathic symptoms, and a second abnormal ENMG showing axonal and myelin neuropathy. One patient had a peroneal nerve biopsy showing loss of large myelinated fibres as well as unmyelinated fibres, and signs of microangiopathy. CONCLUSIONS According to the current recommendations of promptly achieving glycaemic targets, it appears necessary to recognise and understand this neuropathy. Based on our observations and data from the literature we propose an algorithmic approach for differential diagnosis and therapeutic management of APDN patients.

Evidence of axonal reinnervation in two arthropod-borne viral encephalomyelitis patients

Flaviviruses are the main cause of epidemic encephalitis, yet the ratio of inapparent to apparent infections is high, ranging from 20:1 to 1,000:1 [1,2]. When symptomatic, some viruses may cause severe encephalomyelitis that may lead to lasting disability with lower motor neuron paralysis masquerading as poliomyelitis [review in 1, 3]. This syndrome is known as ‘Amyotrophy in Russian spring-summer encephalitis’ (A83) in the classification of neuromuscular disorders of the World Federation of Neurology [4]. We here report 2 patients with such a syndrome, also the subject of another, but clinicoepidemiological, report [5]. The features of our patients are summarized in table 1. Both had neck stiffness with headache, fever greater than 39 ° C, and their cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis with an elevated protein content. Ceftriazone (2 g/day) was started intravenously and the patients improved within 2 days. Both gave a history of insect bite 3 weeks prior to admission. The 3rd day after admission, the patients developed, within hours, bilateral neck, periscapu-lar and brachial muscle weakness and respiratory failure. Both patients required intubation at the end of the 1st week. At the nadir of the disease, examination revealed ventilatory failure, bilateral are-flexic asymmetrical upper limb and neck flexor muscle weakness with amyotrophy, fasciculations, and absence of abdominal cuta-