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1.  Limb lengthening and peripheral nerve function—factors associated with deterioration of conduction 
Acta Orthopaedica  2013;84(6):579-584.
Background and purpose
Limb lengthening is performed for a diverse range of orthopedic problems. A high rate of complications has been reported in these patients, which include motor and sensory loss as a result of nerve damage. We investigated the effect of limb lengthening on peripheral nerve function.
Patients and methods
36 patients underwent electrophysiological testing at 3 points: (1) preoperatively, (2) after application of external fixator/corticotomy but before lengthening, and (3) after lengthening. The limb-length discrepancy was due to a congenital etiology (n = 19), a growth disturbance (n = 9), or a traumatic etiology (n = 8).
Results
2 of the traumatic etiology patients had significant changes evident on electrophysiological testing preoperatively. They both deteriorated further with lengthening. 7 of the 21 patients studied showed deterioration in nerve function after lengthening, but not postoperatively, indicating that this was due to the lengthening process and not to the surgical procedure. All of these patients had a congenital etiology for their leg-length discrepancy.
Interpretation
As detailed electrophysiological tests were carried out before surgery, after surgery but before lengthening, and finally after completion of lengthening, it was possible to distinguish between the effects of the operation and the effects of lengthening on nerve function. The results indicate that the etiology, site (femur or tibia), and nerve (common peroneal or tibial) had a bearing on the risk of nerve injury and that these factors had a far greater effect than the total amount of lengthening.
doi:10.3109/17453674.2013.859418
PMCID: PMC3851673  PMID: 24171677
2.  Intermediate Charcot Marie Tooth disease due to a novel Trp101Stop Myelin Protein Zero Mutation associated with debilitating neuropathic pain 
Pain  2012;153(8):1763-1768.
We report an English kindred affected across four generations with an hereditary neuropathy associated with debilitating neuropathic pain as the main clinical feature. The principal finding on clinical examination was sensory loss and there was variable motor dysfunction. Electrophysiological studies revealed mild features of demyelination with median conduction velocity in the intermediate range. There was an autosomal dominant pattern of inheritance and genetic testing revealed a novel heterozygous Trp101X mutation in exon 3 coding for a portion of the extracellular domain of myelin protein zero (MPZ). This is predicted to lead to premature termination of translation. MPZ is a key structural component of compact myelin, and over a 100 mutations in this protein have been reported which can give rise to neuropathies with either, axonal, demyelinating or intermediate features encompassing a wide range of severity. Chronic pain is an increasingly recognised sequela of certain hereditary neuropathies and may be musculoskeletal or neuropathic in origin. In this kindred the neuropathy was relatively mild in severity however neuropathic pain was an important and disabling outcome.
doi:10.1016/j.pain.2012.05.015
PMCID: PMC3399778  PMID: 22704856
Peripheral Neuropathy; P0 Protein; Myelin; Charcot Marie Tooth Disease; Neuropathic Pain; Quantitative Sensory Testing; Intraepidermal Nerve Fibre Density
3.  Intermediate Charcot-Marie-Tooth disease due to a novel Trp101Stop myelin protein zero mutation associated with debilitating neuropathic pain 
Pain  2012;153(8):1763-1768.
TOC summary
Inherited neuropathies present with striking variety in their phenotype. We present a family with a myelin protein zero mutation and disabling neuropathic pain.
We report an English kindred affected across 4 generations with a hereditary neuropathy associated with debilitating neuropathic pain as the main clinical feature. The principal finding on clinical examination was sensory loss, and there was variable motor dysfunction. Electrophysiological studies revealed mild features of demyelination with median conduction velocity in the intermediate range. There was an autosomal-dominant pattern of inheritance, and genetic testing revealed a novel heterozygous Trp101X mutation in exon 3 coding for a portion of the extracellular domain of myelin protein zero. This is predicted to lead to premature termination of translation. Myelin protein zero is a key structural component of compact myelin, and over 100 mutations in this protein have been reported, which can give rise to neuropathies with either axonal, demyelinating, or intermediate features encompassing a wide range of severity. Chronic pain is an increasingly recognised sequela of certain hereditary neuropathies and may be musculoskeletal or neuropathic in origin. In this kindred, the neuropathy was relatively mild in severity, however, neuropathic pain was an important and disabling outcome.
doi:10.1016/j.pain.2012.05.015
PMCID: PMC3399778  PMID: 22704856
Peripheral neuropathy; MPZ; Charcot-Marie-Tooth disease; Neuropathic pain; Quantitative sensory testing; Intraepidermal nerve fibre density
4.  Multi-minicore disease and atypical periodic paralysis associated with novel mutations in the skeletal muscle ryanodine receptor (RYR1) gene 
Neuromuscular disorders : NMD  2010;20(3):166-173.
The skeletal muscle ryanodine receptor plays a crucial role in excitation–contraction (EC) coupling and is implicated in various congenital myopathies. The periodic paralyses are a heterogeneous, dominantly inherited group of conditions mainly associated with mutations in the SCN4A and the CACNA1S genes. The interaction between RyR1 and DHPR proteins underlies depolarization-induced Ca2+ release during EC coupling in skeletal muscle. We report a 35-year-old woman presenting with signs and symptoms of a congenital myopathy at birth and repeated episodes of generalized, atypical normokalaemic paralysis in her late teens. Genetic studies of this patient revealed three heterozygous RYR1 substitutions (p.Arg2241X, p.Asp708Asn and p.Arg2939Lys) associated with marked reduction of the RyR1 protein and abnormal DHPR distribution. We conclude that RYR1 mutations may give rise to both myopathies and atypical periodic paralysis, and RYR1 mutations may underlie other unresolved cases of periodic paralysis with unusual features.
doi:10.1016/j.nmd.2009.12.005
PMCID: PMC3136116  PMID: 20080402
Multi-minicore disease (MmD); Periodic paralysis; Excitation–contraction coupling (ECC); Skeletal muscle ryanodine receptor (RYR1); gene
5.  A randomised controlled trial investigating the effect of vitamin B12 supplementation on neurological function in healthy older people: the Older People and Enhanced Neurological function (OPEN) study protocol [ISRCTN54195799] 
Nutrition Journal  2011;10:22.
Background
Vitamin B12 deficiency is common in older people and the prevalence increases with age. Vitamin B12 deficiency may present as macrocytic anaemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older people. The diagnosis and indications for treatment are clear for individuals with low plasma levels of vitamin B12 in the setting of megaloblastic anaemia and neuropathy, but the relevance of treatment of vitamin B12 deficiency in the absence of such clinical signs is uncertain.
Methods
The aim of the present study is to assess whether dietary supplementation with crystalline vitamin B12 will improve electrophysiological indices of neurological function in older people who have biochemical evidence of vitamin B12 insufficiency in the absence of anaemia. To test this hypothesis we designed a randomized double-blind placebo-controlled trial involving 200 older people aged 75 years or greater who were randomly allocated to receive either a daily oral tablet containing 1 mg vitamin B12 or a matching placebo tablet. The primary outcome assessed at 12 months is change in electrophysiological indices of peripheral and central neurosensory responses required for mobility and sensory function. We here report the detailed study protocol.
Conclusions
In view of the high prevalence of vitamin B12 deficiency in later life, the present trial could have considerable significance for public health.
doi:10.1186/1475-2891-10-22
PMCID: PMC3062585  PMID: 21396086
6.  Amyotrophic lateral sclerosis with sensory neuropathy: part of a multisystem disorder? 
Sensory involvement is thought not to be a feature of amyotrophic lateral sclerosis (ALS). However, in the setting of a specialist motor neuron disease clinic, we have identified five patients with sporadic ALS and a sensory neuropathy for which an alternative cause could not be identified. In three individuals, sensory nerve biopsy was performed, demonstrating axonal loss without features of an alternative aetiology. These findings support the hypothesis that ALS is a multisystem neurodegenerative disorder that may occasionally include sensory neuropathy among its non‐motor features.
doi:10.1136/jnnp.2006.098798
PMCID: PMC2117693  PMID: 17575021
7.  Functional analysis of Plasmodium falciparum merozoite antigens: implications for erythrocyte invasion and vaccine development. 
Malaria is a major human health problem and is responsible for over 2 million deaths per year. It is caused by a number of species of the genus Plasmodium, and Plasmodium falciparum is the causative agent of the most lethal form. Consequently, the development of a vaccine against this parasite is a priority. There are a number of stages of the parasite life cycle that are being targeted for the development of vaccines. Important candidate antigens include proteins on the surface of the asexual merozoite stage, the form that invades the host erythrocyte. The development of methods to manipulate the genome of Plasmodium species has enabled the construction of gain-of-function and loss-of-function mutants and provided new strategies to analyse the role of parasite proteins. This has provided new information on the role of merozoite antigens in erythrocyte invasion and also allows new approaches to address their potential as vaccine candidates.
doi:10.1098/rstb.2001.1010
PMCID: PMC1692917  PMID: 11839179

Results 1-7 (7)