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The rectal route is indicated to treat patients with rapidly evolving malaria who cannot take oral medication to prevent progression to severe forms of the disease. Improvement can be made in terms of rectal bioavailability and stability of current formulations. We studied a new two-compartment, muco-adhesive gel formulation of artesunate which is adapted for use in children and storage in tropical climates. The formulation contains 50 mg of artesunate per gram of gel. Because of its instability in aqueous solutions, artesunate is in the dry component of the gel with Carbopol® and separate from the liquid phase until reconstitution. Artesunate is stable in the dry blend for 6 months at 45 °C and 60% RH. The gel should be used between 1 and 72 h after being reconstituted. Artesunate release was measured by with a rapid, simple and reliable HPLC-UV which allowed the analysis of artesunate and dihydroartemisinin with an analysis time at 3 min. The amount of artesunate released over 6 h was 56 ± 0.97%. Compared to the reference suspension, total release and dissolution efficiency were lower and rate of release was slower (time to 50% dissolution 271 ± 21 min), probably because of the higher viscosity of the gel, but the drug release profiles were similar. The calculated in vitro release exponent (n) value suggested that artesunate is released from the gel by non-Fickian transport.

Introduction Lambert-Eaton Myasthenic Syndrome (LEMS) is an autoimmune channelopathy in which patients produce autoantibodies directed against voltage-gated calcium channels. LEMS is paraneoplastic in 50% of patients, most frequently associated with small cell lung carcinoma. We describe a case of paraneoplastic LEMS associated with a vocal cord carcinoma. Observation A 64-year-old man developed in five months muscle weakness affecting gait. Clinical examination showed proximal muscular deficiency, areflexia and dysphonia. Electrophysiologic study showed potentiation greater than 500% after post exercise facilitation and 76 percent increment response at high-rate repetitive nerve stimulation (20Hz). Diagnosis of LEMS was confirmed by electrophysiologic study and anti-voltage gated calcium channel antibodies (90pM, positive value greater or equal to 70pM). Left vocal cord lesion histology showed epidermoid carcinoma. A combination of vocal cord tumor removal by endoscopy and treatment by pyridostigmine, 3-4 diaminopyridine and intravenous human immunoglobulin improved neurological symptoms. Conclusion Paraneoplastic syndromes in association with cancers of the larynx and hypopharynx are unusual. Only two cases are reported with LEMS associated with larynx carcinoma. We describe an unusual case of LEMS associated with a left vocal cord carcinoma.

Churg-Strauss syndrome (CSS) is a distinctive clinical entity in which systemic vasculitis, associated with eosinophilia, occurs almost exclusively in individuals with adult-onset asthma. The major complications of the condition result from damage to the lungs, heart, and peripheral nerves. Necrotizing vasculitis with eosinophils in the cellular infiltrate, vascular or perivascular infiltration by eosinophils in absence of vessel wall necrosis, extra-vascular eosinophil infiltrates, and vascular or extra-vascular granuloma are histopathological features supportive of CSS. As the peripheral nerve disease often dominates the clinical picture, the peripheral nerve biopsy may be decisive in establishing the diagnosis. In this retrospective study of neuro-muscular biopsies in 24 CSS cases, the authors give an extensive description of neuropathological lesions associated with this disorder. Fifteen patients (62.5%) exhibited eosinophils either in extra-vascular infiltrates or in vessel walls, and 6 of them (25%) had an associated necrotizing vasculitis. Granulomas were found in only 3 cases (12.5%). The clinical diagnosis of CSS was supported in 15 out of the 24 patients (62.5%), in the nerve in 2 cases (8.3%), in the muscle in 8 cases (33.3%), and in both nerve and muscle in 5 others (20.8%).

A 35-year-old man had prolonged occupational exposure to lead carboxylate, triethylbenzene, xylene, and dichloromethane, when he developed a subacute predominantly sensory neuropathy. Ultrastructural examination of a peripheral nerve biopsy showed axonal degeneration and unusual lesions of the myelin, with Schwann cell sequestration of vesicular and lamellar debris. Biochemical analysis of lead in a frozen peripheral nerve specimen revealed no significant difference between the propositus and a control. The authors were unable to find any similar peripheral nerve lesions in the literature dealing with neurotoxic chemicals. Any of the several organic solvents could have equally caused the neuropathy and may have been potentialized by the other chemicals.

We performed a retrospective study of 35 peripheral nerve biopsies (PNBs) with amyloid deposits in the endoneurium. In every case, nerve lesions were studied on paraffin-embedded fragments (PEFs) and by ultrastructural examination (USE). In addition, muscle fragments were taken and embedded in paraffin. Immunohistochemistry was performed with anti-transthyretin (TTR) serum on 19 nerve and 15 muscle PEFs. Direct immunofluorescence with anti-light-chain sera was performed on frozen nerve fragments in 19 cases. Endoneurial amyloid deposits were easily identified on routine PEF in 26 cases, after Congo red or thioflavine staining in three, and by USE in six. A dramatic myelinated fiber loss was evidenced in 34 cases (77-2970 per mm2), and features of axonal degeneration were present in every case. Segmental demyelination was observed in 10 cases. A mutation in the TTR gene was present in 14 cases, with Met30 mutation in 10 and Ala49 in four members of the same family. Amyloid deposits were strongly marked by the anti-TTR serum in 11 other cases, twice in the endoneurium, five around muscle fibers, and four in both locations. In eight patients, light-chain positivity was evidenced in endoneurial deposits, lambda in six and kappa in two. Two other patients with monoclonal gammopathy did not present any light-chain fixation. In 17 cases, amyloidosis was disclosed by PNB and 13 had a TTR pathology; eight of them, over 65 years old, correspond to a late-onset form of familial amyloid polyneuropathy which is an underdiagnosed condition.

In most cases of hereditary neuropathy with liability to pressure palsy (HNPP) the diagnosis is now assessed by molecular detection of 17p11.2 deletion. However, the family history may be missing and the clinical presentation is not always informative. In such cases, a peripheral nerve biopsy showing the characteristic focal myelin sheath thickening ("tomaculae") may be helpful. We present a retrospective study of peripheral nerve biopsies performed in 19 patients suffering from either a mononeuropathy or a generalized sensory-motor polyneuropathy, and for whom the finding of tomaculae led to a search for 17p11.2 deletion, which was confirmed secondarily. Tomaculae and other coexisting neuropathological lesions such as uncompacted myelin, "onion bulb" formations, and axonal degeneration are described and discussed in the view of previously reported data. It appears that demyelinating lesions with tomaculae are strongly suggestive of HNPP but are not specific as they may be observed in other conditions. Moreover, these features may be overlooked if axonal degeneration is marked.

Resume POEMS est un acronyme pour polyneuropathie, organomegalie, endocrinopathie, proteine monoclonale et signes cutanes (« skin changes » en anglais). Il est egalement denomme syndrome de Crow-Fukase principalement au Japon. Le plus souvent, les cinq elements du syndrome ne sont pas tous presents au moment du diagnostic, et les criteres minimum pour etablir le diagnostic sont la presence d’une neuropathie demyelinisante et axonale, associee a une gammapathie monoclonale IgG ou IgA, avec une chaine legere qui est presque toujours lambda, et au moins 2 des 8 autres signes du syndrome : plasmocytome sclerosant, endocrinopathie, lesions cutanees, organomegalie, maladie de Castleman, anasarque, œdeme papillaire ou thrombocytose. Aucun de ces signes n’est specifique, a l’exception des angiomes cutanes glomeruloides. L’identification ultrastructurale de lamelles de myeline non compactes sur la biopsie de nerf peripherique est, dans le contexte clinique, un element important en faveur du diagnostic. Une lesion osseuse habituellement osteocondensante doit etre soigneusement recherchee car son traitement peut ameliorer les autres signes du syndrome et specialement la neuropathie. Les cytokines et le facteur de croissance vasculaire endothelial pourraient jouer un role dans la pathogenie incompletement elucidee de cette affection multisystemique rare.

We report a case of Charcot-Marie-Tooth disease (CMT), with identified PMP22 gene duplication (CMT type 1A), and with evidence of an inflammatory demyelinating process superimposed on the course of the chronic genetic disease. Macrophage-associated demyelination was observed on the peripheral nerve biopsy. This observation supports some experimental data from the literature and shows that there may be a genetic susceptibility to inflammatory demyelinating processes in certain CMT kindreds.

Background: Peripheral neuropathy is known to be related to inflammatory bowel disease and it is one of the most frequently reported neurologic complications. Various studies have found peripheral nervous system complications, rather than central nervous system involvement, to be predominant. In the literature, there are a few cases of inflammatory polyneuropathy developed in the course of ulcerative colitis : 5 cases of Guillain-Barre syndrome, one case of chronic inflammatory demyelinating polyneuropathy, 10 cases of neuropathy and one case of perineuritis. Case presentation: We describe a case of chronic inflammatory polyneuropathy associated with ulcerative colitis. Conclusion: Peripheral neuropathy is not a common manifestation of IBD, highlighting the need for careful exclusion of other causes of neuropathy when both conditions are encountered in clinical practice.

Forty-three cases of peripheral neuropathy (PN) have been reported in the literature with a proven mitochondria (mt) DNA mutation, and 21 had a peripheral nerve biopsy (PNB). We studied 8 patients, 1 of whom had severe sensory PN, 3 mild PN, and 4 subclinical PN. Nerve biopsy was performed in every case; all patients showed axonal degeneration and 4 showed features of primary myelin damage. In addition, there were 2 crystalline-like inclusions in the Schwann cell cytoplasm of a patient with MERRF, and 1 in a patient with multiple deletions on the mtDNA. There are 11 cases of PNB in the literature with axonal lesions, 5 with demyelination, and 4 with mixed lesions. One PNB was not modified. A few crystalline-like inclusions were seen in 1 case of MERRF. Such inclusions were first reported in the Schwann cell cytoplasm of unmyelinated fibers in a patient with Refsum disease and were considered to be modified mitochondria. However, their mitochondrial origin remains debatable.

Clinical, electrophysiological, and neuropathological features are reported associated with a novel heterozygote point mutation in the extracellular domain of the MPZ gene, where a transversion at codon 71 in exon 3 leads to a codon stop: Glu71stop (ie GAA→TAA). A 36 year old woman developed a mild recurrent neuropathy after intensive manual work. The motor nerve conduction velocities were slow without conduction blocks and the nerve biopsy showed signs of demyelination-remyelination, axonal loss, and regular uncompacted myelin lamellae. She inherited the mutation from her father who displayed the same mutation with a normal phenotype. This nonsense mutation may cause a dosage difference of normal P0, and is probably underrepresented in the current mutation data bases. This report further extends the phenotype of MPZ mutations and also emphasises that mild phenotype of CMT1B may be more frequent than has been appreciated.

It is well known that patients with Charcot-Marie-Tooth (CMT) disease are liable to present with episodes of cortisone-responsive demyelination, and a superimposed inflammatory component has been suggested. We report a patient who presented with a chronic inflammatory demyelinating polyneuropathy due to a recent HIV infection, which revealed a previously asymptomatic CMT 1A disease documented by identification of the characteristic duplication on the p11.2 region of chromosome 17. The inflammatory process was characterized by pathologic findings on a superficial peroneal nerve biopsy, and the patient improved significantly after corticotherapy. This report gives support to the hypothesis of a genetic susceptibility to inflammatory demyelinating processes in certain CMT kindreds.

The authors recently reexamined the peripheral nerve biopsies from 42 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). There were 27 males and 15 females, aged from 9 to 84 years, and 13 had relapses. No patient had vasculitis, monoclonal gammopathy, tumor, diabetes mellitus, Lyme disease, familial neuropathy, HIV, or any other immune deficiency. In the endoneurium, perivascular inflammatory cell infiltrates were present in only one case, but scattered histiocytes marked by KP1 on paraffin-embedded fragments were present in every case and there were no T-lymphocytes. At ultrastructural examination macrophage-associated demyelination was observed in 17 cases, of which 6 had relapses separated by intervals of several months or years. Axonal lesions without associated primary demyelination were observed in 4 cases and 3 of these had relapses. Thirty-two patients had mixed lesions of demyelination and axonal involvement. This study confirms other recent data indicating that in all cases of CIDP, macrophages are present in the endoneurium. Macrophage-associated demyelination is the characteristic feature of demyelinating forms. On the other hand, isolated primary axonal forms, which have been known since 1989, are relatively frequent and prone to relapses.

Copper deficiency may cause myeloneuropathy or progressive limb weakness. By contrast, Wilson's disease (WD) is characterized by progressive copper accumulation with hepatic and neurological impairment and requires life-long treatment with zinc and/or chelator agents. We report a WD patient who developed axonal sensory motor neuropathy in the context of copper deficiency due to his treatment with zinc and chelators. Exhaustive testing for other etiologies was negative. After treatment adjustment, only mild clinical improvement was noted during long-term follow-up. Muscle Nerve 40: 294-296, 2009.