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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. Muscle Nerve 28: 373–376, 2003 [ABSTRACT FROM AUTHOR]

The EDTA and sodium caprate (Na caprate) effects on the oral bioavailability of norfloxacin were tested. It was found that absorption kinetic of norfloxacin was markedly accelerated when mixed with EDTA or Na caprate in a ratio of 1:1. When mixed with the absorption enhancers in a ratio of 1:5, only Na caprate improved norfloxacin bioavailability significantly. In vitro dissolution tests demonstrated that EDTA and Na caprate increased norfloxacin dissolution kinetic. However, the correlation between bioavailability and in vitro dissolution improvement was not clearly established. So, we can conclude that the solubilizing property of EDTA and Na caprate did not take a prominent part in norfloxacin absorption. [Copyright &y& Elsevier]

Abstract There is still confusion as to whether X-linked Charcot-Marie-Tooth disease (CMTX) is primarily an axonal disorder or is primarily demyelinating. Eight symptomatic patients, 7 males and 1 female, from 6 families with identified connexin32 mutations underwent a superficial peroneal nerve biopsy. Quantitative and ultrastructural studies were performed, and histopathological lesions in these 8 patients proved to be quite homogeneous. The myelinated fiber count was within normal values or only moderately decreased. In 7 cases, the distribution of myelinated fibers was unimodal due to a loss of large fibers, coexisting with numerous clusters of small regenerating fibers. At ultrastructural level, these clusters were often surrounded by flattened Schwann cell processes giving an aspect of “pseudo-onion bulb” formation. There was no “naked axon” (ie, demyelinated axon), and real “onion bulb” formations composed of flattened Schwann cell processes surrounding an isolated myelinated fiber were discrete and not numerous. Macrophages laden with myelin debris were scarce or absent in the endoneurium. Several fibers appeared discretely hypomyelinated and the calculated g-ratio was scarcely higher than the mean control value. Lesions of unmyelinated fibers were absent in 7 cases and mild in one. Given that the primary defect concerns connexin32, we think that the histopathological features observed in our patients correspond to primary hypomyelination rather than to ongoing demyelination. The associated axonal degeneration might be secondary to defective axon-Schwann cell interactions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Botulinum toxin (BTA) is a safe and effective therapeutic tool for many neurological conditions but few studies have investigated its real cost in neurological practice. We evaluated the daily cost of botulinum toxin type A (BTA) treatment through a cost effectiveness analysis alongside a prospective study of BTA injections at a French University Hospital over a 2-year follow-up period. The data of 3,108 BTA injections performed in 870 adult patients presenting with dystonia, facial hemispasm, or spasticity were entered in the database. Patients were questioned at each visit about the subjective effectiveness of the previous injection. The daily cost of BTA treatment was calculated as the ratio of each session's cost (including all additional costs) to the duration of subjective efficacy. The subjective rating of efficacy duration was 17.3 ± 7.7 weeks for facial hemispasm, 15.4 ± 7.7 for blepharospasm, 14.3 ± 6.7 for cervical dystonia, 14.5 ± 7.8 and 14.1 ± 7.4 weeks for upper and lower limb spasticity, respectively. The daily cost of BTA injections was 0.57 ± 0.20 € for facial hemispasm, 0.95 ± 0.30 € for blepharospasm, 2.85 ± 0.86 € for cervical dystonia, 3.38 ± 1.49 € and 3.62 ± 1.81 € for upper and lower limb spasticity, respectively. When associated costs were considered, the daily cost of BTA injections was clearly increased (45-93%) in limb spasticity or rigidity but remained only modestly increased (15-37%) in other indications. These results obtained in a large cohort of patients show that BTA treatment has a low daily cost for a long-lasting effect, with a daily cost/benefit ratio that greatly depends on the indications. [ABSTRACT FROM AUTHOR]

Abstract: Artemisinin-based combination therapies, including artesunate (AS)+amodiaquine (AQ), are the currently recommended first-line treatment of uncomplicated falciparum malaria. Fixed-dose co-formulations offer logistic and adherence advantages. This paper reports the initial research phase of the pre-development process of an AS–AQ formulation, further developed by the Drug for Neglected Diseases Initiative (DNDi). Results demonstrate that AS and AQ are not compatible, and AS degradation is related to three main parameters: water content (>1%), elevated temperature (80°C in dry condition) and possibly the 4-aminoquinoline moiety. Furthermore, AS and AQ incompatibility led to AS degradation and pharmaco-technical changes in classical wet granulation tablets. Both active principles are stable as dry powders. These investigations led to further development of various co-formulations, including the bilayer tablet currently on the market. [Copyright &y& Elsevier]

Some patients fulfilling the criteria for the diagnosis of multifocal motor neuropathy with conduction block (MMN-CB) at the onset of disease may subsequently develop a sensory loss associated with electrophysiological sensory abnormalities. The latter could represent an overlap between MMN-CB and multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy. The objective was to specify the features of MMN-CB with sensory loss (MMN-CB-Se). Five patients in a series of 11 consecutive patients who fulfilled the criteria of the American Association of Neuromuscular and Electrodiagnostic Medicine for MMN-CB at the first examination and were treated periodically with intravenous immunoglobulin (IVIg) developed sensory loss in the course of the disease. In these five patients we compared the clinical, laboratory, and electrophysiological features found after the development of sensory loss with those at the first examination. The mean time to appearance of objective sensory signs was 7.2 years. In three of the five patients the sensory loss was preceded by intermittent paresthesias in the same nerve territories as the motor involvement. The most frequent electrophysiological abnormality was amplitude reduction of sensory nerve action potentials. There were no bilateral or symmetrical clinical and electrophysiological sensory abnormalities. Anti-GM1 IgM antibodies were positive in four patients. MMN-CB-Se could be an overlap between MMN-CB and MADSAM. It shares the distribution of the sensory disorders encountered in MADSAM, but it is closer to MMN-CB on clinical and therapeutic levels. Study of more patients would be useful to classify this subgroup more accurately. Muscle Nerve, 2009 [ABSTRACT FROM AUTHOR]

Abstract: 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 50mg 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 72h 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 3min. The amount of artesunate released over 6h 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±21min), 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

We reviewed 202 biopsies performed on patients with suspected vasculitic neuropathy, of which 24 Churg-Strauss cases are studied separately. Specimens from the superficial peroneal nerve and peroneus brevis muscle were taken simultaneously by one incision. Without taking into account constitutional signs, systemic involvement was present in 131 patients, whereas the remaining 47 corresponded to non-systemic patients with lesions limited to peripheral nervous system and adjoining muscles. Diagnosis of panarteritis nodosa or microscopic polyangiitis, according to the size of involved vessels, was attested by an infiltration of vessel walls by inflammatory cells associated with fibrinoid necrosis or sclerosis. Microvasculitis was diagnosed when inflammatory infiltration concerned small vessels with few or no smooth-muscle fibers and without any necrosis. Microvasculitis was present in 11 of 46 non-systemic cases, and this predominance is statistically significant. Isolated perivascular cell infiltrates in the epineurium were considered not significant but allowed the diagnosis of ‘probable vasculitis’ if associated with at least one of the following features: regenerating small vessels, endoneurial purpura, asymmetric nerve fiber loss, and/or asymmetric acute axonal degeneration. Necrotizing vasculitis was visible in 60 cases: in nerve (16 cases), in muscle (19 cases), and both (25 cases). Microvasculitis was present in 25 cases: in nerve (19 cases), muscle (four cases), or both (two cases). Moreover, granulomatous vasculitis was found in the nerve of one non-systemic patient presenting also sarcoid granulomas in muscle. There were 24 ‘probable vasculitis’ and 68 negative cases. Muscle biopsy improved the yield of definite vasculitis by 27%. [ABSTRACT FROM AUTHOR]

We examined nerve biopsies from 24 patients with Charcot-Marie-Tooth disease type 1A (CMT1A) and proven 17p11.2-12 duplication. There were seven males and 17 females with a mean age of 27.85 ± 18.95 years at the time of nerve biopsy. A family history consistent with dominant inheritance was present in 17 patients. Clinical features were classical in 16 patients and were atypical in the other eight: one had calf hypertrophy; two had Roussy–Levy syndrome; one had had a subacute inflammatory demyelinating polyneuropathy 11 years earlier and presented a relapse on the form of a chronic inflammatory demyelinating polyneuropathy; one had carpal tunnel syndrome; one had a recent painful neuropathy in both legs; and two had chronic inflammatory demyelinating polyneuropathy. Onion bulb formations (OMFs) were present in every case and most of them were characteristic, whereas burnt-out or cluster-associated OMFs were less common. Depletion of myelinated fibers was severe in 20 cases (169–2927/mm2) and varied from 5187 to 3725/mm2 in three children (4–9 years old). In addition, features of macrophage-associated demyelination were observed in the last four atypical cases. Known for more than 20 years, inflammatory demyelination superimposed in the course of CMT1A has been reported in a few cases in the past few years, mainly concerning asymptomatic or atypical patients. Such an association deserves to be better known because corticotherapy improves weakness in most of these patients. [ABSTRACT FROM AUTHOR]

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 REF 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 TYR 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 RNB 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. [ABSTRACT FROM AUTHOR]

Abstract The pathogenesis of Crow–Fukase (POEMS) syndrome is not well known, and in some cases, a definite diagnosis is difficult to establish. Nerve fibers have been studied in about 120 peripheral nerve biopsies (PNBs), and a mixture of axonal and demyelinating lesions were found in most of them. We report five new cases of Crow–Fukase (POEMS) syndrome with ultrastructural examination of their PNBs. In every case, there were features of axonal degeneration and primary demyelination. Interestingly, uncompacted myelin lamellae (UMLs) were present in every case at a percentage of 1–7. The association of UML and Crow–Fukase (POEMS) syndrome was described 20 years ago but was only reported in a few studies and found in 31 of 41 cases. In fact, this association is very significant because apart from Crow–Fukase (POEMS) syndrome, UMLs can only be found with such a frequency in rare cases of Charcot–Marie–Tooth disease type 1B. UML was also reported in acute and chronic inflammatory demyelinating polyneuropathies but at a much lower percentage. Moreover, in our five cases, UML was frequently associated with a decrease in the number of intra-axonal filaments, and this finding raises the problem of relationships between myelin formation and neurofilaments. So far, glomeruloid hemangiomas present in the dermis of some patients are considered as the only specific criteria of Crow–Fukase (POEMS) syndrome, but we think UML can also be regarded as highly suggestive of this entity on condition that a thorough ultrastructural examination of a PNB is performed. [ABSTRACT FROM AUTHOR]

Presents a three-category classification of uncompacted myelin lamellae (UML) in peripheral nerve biopsy based on its ultrastructural pattern. Display of regular UML in 43 cases in the first category; Inclusion of irregular UML in the second category with one benign case and three B-cell malignant lymphomas; Presence of complex UML in two unrelated patients with an Arg 98 in the third category.

Abstract 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. [ABSTRACT FROM AUTHOR]

We studied the efficacy of endoscopic injection of Botulinum A toxin (150 I.U. Dysport®) in the treatment of detrusor-sphincter dyssynergia in 17 patients with spinal cord disease. One month after the injection, the postvoiding residual urine volume (-176 ml, P<0.001), the bladder pressure on voiding (-19 cm water, P<0.01), and the urethral pressure (-24 cm water, P<0.001) were significantly decreased. The modality of voiding was improved in 10 patients (ie micturition by suprapubic tapping was easier to induce, discontinuation of indwelling catheter use, or decrease in frequency of intermittent catheterizations). The tolerance of the treatment was excellent. The therapeutic effect lasted 2 to 3 months on the average. The low doses used in this study probably explain in part why the treatment sometimes failed. Botulinum A toxin could become an alternative treatment for detrusor-sphincter dyssynergia in certain patients, notably in those who are refractory to sphincterotomy or in patients, such as those who are tetraplegic, and who are incapable of performing intermittent self-catheterization. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

A letter to the editor is presented titled "Long-term improvement of paroxysmal dystonic choreathetosis with acetazolamide," by Veronique Michel and others in the Journal of Neurology vol. 253, 2006 issue.

A letter to the editor is presented about a case study of Retrobulbar optic neuritis: a complication of lyme disease.