A new treatment that uses two old drugs together may offer hope of relief to millions of North Americans who suffer neuropathic pain.
A type of chronic stabbing, burning pain, neuropathic pain is often a mystery to health care workers. But it is a real and debilitating illness for patients who report being unable to work, sleep or concentrate.

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Brain. 2005 Mar 17
Li J, Bai Y, Ghandour K, Qin P, Grandis M, Trostinskaia A, Ianakova E, Wu X, Schenone A, Vallat JM, Kupsky WJ, Hatfield J, Shy ME.
Skin biopsy is a minimally invasive procedure and has been used in the evaluation of non-myelinated, but not myelinated nerve fibres, in sensory neuropathies. We therefore evaluated myelinated nerves in skin biopsies from normal controls and patients with Charcot-Marie-Tooth (CMT) disease caused by mutations in myelin proteins. Light microscopy, electron microscopy and immunohistochemistry routinely identified myelinated dermal nerves in glabrous skin that appeared similar to myelinated fibres in sural and sciatic nerve. Myelin abnormalities were observed in all patients with CMT. Moreover, skin biopsies detected potential pathogenic abnormalities in the axolemmal molecular architecture previously undetected in human neuropathies. Finally, myelin gene expression at both mRNA and protein levels was evaluated by real-time PCR and immunoelectron microscopy. Peripheral myelin protein 22 (PMP22) was increased in CMT1A (PMP22 duplication) and decreased in patients with hereditary neuropathy with liability to pressure palsies (PMP22 deletion). Taken together, our data suggest that skin biopsy may in certain circumstances replace the more invasive sural nerve biopsy in the morphological and molecular evaluation of inherited and other demyelinating neuropathies.

No vitamin C trials are planned in Germany; researchers from the University of Tuebingen are critical of the success, on the grounds that when taking a high dose of Vitamin C each person will feel more energetic and need less sleep. However, Italian Vitamin C trials begin January 2005, so more information is yet to come.

From CMTUS comes word of a Med Sci (Paris) article about the effects of ascorbic acid (vitamin C) on CMT1A in mice. Transgenic mice with the disease given ascorbic acid performed significantly better on treadmill and muscle grip tests. Furthermore, nerve biopsies of the sciatic nerve showed remyelination of the nerves with normal-shaped myelin.
Though this study focused on CMT1A, it might have ramifications for Dejerine-Sottas (considered by some to be CMT3) as the gene they focused on was PMP22, which is also affected in Dejerine-Sottas. Please do not take this article as medical advice and self-medicate without consulting your doctor; further studies need to be done.
Click “more” to read the translated article.

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An article about Dejerine-Sottas from the Sao Paulo Medical Journal has been made available online through SciELO, an electronic virtual library covering a selected collection of Brazilian scientific journals. Abstract available in English and Portuguese, article available in English as a PDF.

MARINHO, Jaqueline Luvisotto, ALONSO NIETO, José Luis and CALORE, Edenilson Eduardo. Dejerine-Sottas disease: a case report. Sao Paulo Med. J. [online]. 2003, vol.121, no.5 [cited 16 January 2004], p.207-209. Available from World Wide Web: <http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-31802003000500006&lng=en&nrm=iso>. ISSN 1516-3180.

According to this article, those in Aspen, CO on Tue., August 19, can attend a free lecture at the Given Institute on "The Boundless Potential of Peripheral Nerve Regeneration", as part of their summer public lecture series. Though the lecture will focus on carpal-tunnel syndrome, cut nerves, and microvascular surgery breakthroughs, the article also mentions that researchers are finding "faster and better" methods of growing Schwann cells in the laboratory.

I have so many questions about this article. What do they mean by abnormally folded myelin sheaths, in an "onion bulb" pattern? Does dystroglycan play a role in Dejerine-Sottas? Are nodes of Ranvier affected?

Each Schwann cell envelops a short stretch of axon, and the gaps between each section of the myelin sheath are called nodes of Ranvier. Ions flow through sodium channels at these nodes generating action potentials or nerve impulses. This signal is transmitted down the nerve fiber from one node to the next.
The researchers found that dystroglycan is necessary to form normal myelin sheaths. They also discovered that loss of the protein disrupts the structure of the nodes of Ranvier and affects the nerve?s ability to transmit nerve impulses. The results suggest that disruption of dystroglycan’s functions may play a role in various neuropathic disorders.
The UI team developed mice that lacked dystroglycan in their Schwann cells. This specific mutation caused progressive nerve damage in the mice. The mice were less coordinated than normal mice and their sensitivity to heat and pressure was altered. The team also showed that nerve impulses traveled more slowly in these mice.
The researchers examined the peripheral nerve fibers and saw that the myelin sheaths were abnormally folded, indicating that dystroglycan is important for normal myelination of peripheral nerve. This finding was not unexpected, as several earlier studies had suggested that dystroglycan might be involved in myelination.
However, the myelin sheath abnormalities did not seem severe enough to account for the significant reduction in the speed of nerve impulses in the mutant mice. This puzzle led the researchers to another discovery: the absence of dystroglycan appears to disrupt the normal structure of the nodes of Ranvier that are necessary to rapidly transmit nerve impulses along the nerve. In particular, loss of dystroglycan reduces the density of sodium channels that cluster at each node and are critical for normal transmission of nerve impulses.

Dejerine-Sottas Neuropathy with Multiple Nerve Roots Enlargement and Hypomyelination Associated with a Missense Mutation of the Transmembrane Domain of MPZ/P0.
Simonati A, Fabrizi G, Taioli F, Polo A, Cerini R, Rizzuto N.
Journal of Neurology 249: 1298-1302, 2002. Reprinted with permission from Dr. Dietrich Steinkopff Verlag.
In a patient affected with a slowly progressive, severe form of Dejerine-Sottas syndrome, symmetric enlargement of cranial nerves and focal hypertrophy of cervical and caudal roots were detected following MRI. Neuropathological features of the sural nerve disclosed a dramatic loss of myelinated fibres, with skewed-to-the-left, unimodal distribution of the few residual fibres, consistent with the diagnosis of congenital hypomyelination neuropathy. Genetic analysis revealed this condition to be associated with a heterozygous G to A transition at codon 167 in the exon 4 of the MPZ/P0 gene causing a Gly138Arg substitution in the transmembrane domain of the mature MPZ/P0 protein. Focal enlargement of the nerve trunks in demyelinating, hereditary motor and sensory neuropathies (HMSN) was previously reported in both asymptomatic and symptomatic cases with root compression, but peculiar to this case is the diffuse involvement of both cranial and spinal nerves. We believe that the relevance of nerve trunk hypertrophy in HMSN is probably underevaluated: therefore MRI investigation of the head and spine should be included in the diagnostic study of selected HMSN patients. Molecular analysis of peripheral myelin genes will help to rule out misdiagnosed cases.