Biomedical subjects

Kerry R Mills

Publications and source records attributed to Kerry R Mills.

7 recordsLinked to original sources

PubMed2006

Clinical electrophysiological characterization of the acquired neuromyotonia phenotype of autoimmune peripheral nerve hyperexcitability.

Acquired autoimmune neuromyotonia is regarded as part of the spectrum of peripheral nerve hyperexcitability disorders. We aimed to use clinical neurophysiological measurements to study the extent, distribution, and characteristics of spontaneous motor unit potentials in 11 patients with acquired neuromyotonia. Investigations revealed that most spontaneous discharges recorded were motor unit, or partial motor unit potentials of normal size. Bursts of motor unit potentials arose more commonly from distal portions of the peripheral nerve and had abnormal absolute and relative refractory periods. Spontaneous discharges in some patients occurred in semirhythmic bursts in certain muscles. No patient had neurophysiological abnormalities detectable in first-order neurons of the central nervous system when using transcranial magnetic stimulation to estimate the threshold for corticomotor excitation and determine central motor conduction time. Only patients with coexistent myasthenia gravis had neurophysiologically detectable defects in neuromuscular transmission. The pathogenic region of abnormality in peripheral nerve hyperexcitability disorders therefore seems to lie within the terminal branches of peripheral motor nerves.

Action Potentials↗

PubMed2006

Multifocal acquired demyelinating sensory and motor neuropathy presenting as a peripheral nerve tumor.

A man with multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), or Lewis-Sumner syndrome, presented with a progressive left lumbosacral plexus lesion resembling a neurofibroma. After 7 years he developed a left ulnar nerve lesion with conduction block in its upper segment. Treatment with intravenous immunoglobulin improved the symptoms and signs of both lesions. We conclude that inflammatory neuropathy must be considered in the differential diagnosis of peripheral nerve tumors, and that unifocal lesions may precede multifocal involvement in MADSAM by several years. In addition, we discuss the clinical features in 9 patients attending a specialist peripheral nerve clinic and review the literature.

Brachial Plexus Neuropathies↗

PubMed2006

The effect of valproate on silent period and corticomotor excitability.

OBJECTIVE: To investigate, by transcranial magnetic stimulation, the effects of valproate on silent period and corticomotor excitability. METHODS: thirty patients with generalized epilepsy were studied at baseline, and re-examined 4 (S1) and 25 (S2) weeks after the administration of valproate (mean dose: 1040 +/- 284 mg). Transcranial magnetic stimulation was performed with a figure of eight coil (recording, first dorsal interosseous). Threshold was measured at 1% steps. Silent period was measured using a recently described protocol. Briefly, silent periods were elicited at 5% increments from 0 to 100% maximum stimulus intensity. At each stimulus intensity, 4 silent periods were obtained and the average value of silent period duration was used to construct a stimulus/response curve of stimulus intensity versus silent period. The resulting curves were then fitted to a Boltzman function and were statistically compared. The motor-evoked potential recruitment curve was constructed under active conditions and analyzed in a similar way. RESULTS: Valproate increased threshold from 36.5 +/- 5.99% at baseline to 41.02 +/- 7.84% at S1 (p < 0.0001, paired t-test). The maximum value of the silent period curve decreased from 257.5 +/- 3.9 ms at baseline to 230.3 +/- 3.9 ms at S1 (p < 0.0001, F-test and AIC) while the other best-fit values (V(50), slope, threshold) were not significantly affected. Regarding the motor-evoked potential recruitment curve, the maximum value decreased significantly post-drug (from 0.449 +/- 0.007 to 0.392 +/- 0.009, p < 0.01, F-test and AIC test), whereas the rest of the best-fit values remained unaffected. CONCLUSION: In patients with idiopathic generalized epilepsy, valproate increases threshold and reduces the maximum values of the silent period curve and the motor-evoked potential recruitment curve. These findings probably reflect valproate's effects on voltage-dependent Na(+) channels, as well as an activation of GABA(A) receptors.

Adolescent↗

PubMed2004

A novel central motor conduction abnormality in D90A-homozygous patients with amyotrophic lateral sclerosis.

Patients with amyotrophic lateral sclerosis (ALS) who are homozygous for the D90A SOD1 mutation have been noted to have central motor abnormalities distinct from those of patients with idiopathic ALS. We stimulated the motor cortex of ten patients homozygous for the D90A SOD1 mutation, using transcranial magnetic stimulation (TMS), and recorded the response evoked in the right first dorsal interosseous muscle when the muscle was at rest and when voluntarily active. A subgroup of patients had two distinct evoked responses when the cortex was stimulated at high intensity with the muscle at rest. When the muscle was modestly contracted, the first of these responses disappeared, whereas the second response was facilitated. Both fast and slow components of the corticospinal tract were usually intact and excited by TMS in these patients. We propose that there is an abnormality of intracortical or intraspinal inhibition in a subgroup of D90A SOD1 ALS patients, which suppresses fast-conducted activity when the muscle is active. Apart from further defining the phenotype of familial ALS, these findings may have importance in understanding the pathogenesis of central motor abnormalities in these patients.

Adult↗

PubMed2004

Autosomal recessive spinocerebellar ataxia and peripheral neuropathy with raised alpha-fetoprotein.

We describe three patients from two families with progressive spinocerebellar ataxia, peripheral neuropathy, raised alpha-fetoprotein (AFP) and hypercholesterolaemia. Two siblings had identical clinical features, with late childhood onset of symptoms and slow progression, requiring crutches to walk at ages 37 and 38 years. Another patient developed ataxia aged 13 years and became wheel-chair bound by 20 years of age. Although they all had raised serum AFP levels, their clinical, immunological, biochemical, cytogenetic and molecular genetic studies failed to support a diagnosis of Ataxia Telangiectasia. Extensive investigation including imaging, biochemical and genetic studies excluded other known ataxias. Their clinical features most closely resemble the phenotype of a single consanguineous Japanese family with four individuals affected by spinocerebellar ataxia, peripheral neuropathy, raised AFP and hypercholesterolaemia. Homozygosity mapping has identified a locus in this Japanese family at 9q34. Haplotype analysis of our cases demonstrated possible linkage to 9q34, suggesting these may be the first Caucasian families described with this disorder.

Adult↗

PubMed2004

Optimising the detection of upper motor neuron function dysfunction in amyotrophic lateral sclerosis--a transcranial magnetic stimulation study.

Evidence of upper motor neuron (UMN) dysfunction is essential in making the diagnosis of amyotrophic lateral sclerosis (ALS). Central motor conduction (CMC) abnormalities detected using transcranial magnetic stimulation (TMS) are presumed to reflect UMN dysfunction. CMC is, however, often normal in patients with classical sporadic ALS. The aim of the study was to determine whether the utility of the CMC measure in ALS could be enhanced. We measured CMC to four pairs of muscles (abductor digiti minimi (ADM), biceps, vastus medialis (VM) and abductor hallucis (AH) in 20 controls and 25 ALS patients. The commonest abnormality detected in the ALS patients was an absent MEP, found in 11 patients (44 %) and in 25 of 200 muscles examined. Studying a minimum of three muscles increased the probability of detecting UMN dysfunction. Weakness in the muscle as well as selecting a distal rather than a proximal muscle was significantly associated with an abnormal CMC. Interside differences in CMC were significantly more pronounced in the patient group. In 30% of patients a significant interside difference in AH CMC time was the sole abnormality, suggesting mild UMN dysfunction on the side with the longer CMC.

Adult↗

PubMed2002

Phenotypic variants of autoimmune peripheral nerve hyperexcitability.

Clinicians use many terms including undulating myokymia, neuromyotonia, Isaacs' syndrome and Cramp-Fasciculation Syndrome to describe the motor manifestations of generalized peripheral nerve hyperexcitability (PNH). Our previous findings in a selected group of patients with undulating myokymia or neuromyotonia, and EMG doublet or multiplet ('myokymic') motor unit discharges, indicated that an autoantibody-mediated potassium channelopathy was likely to be the cause of their disorder. This prompted us to search for a common pathogenesis in a wider spectrum of PNH syndromes. We studied the clinical, autoimmune and electrophysiological features of 60 patients presenting with acquired PNH. Patients were grouped according to an EMG criterion: the presence (group A, n = 42) or absence (group B, n = 18) of doublet or multiplet myokymic motor unit discharges. The average ages of onset in the two groups were 45 and 48 years respectively. The relative frequency and topography of the clinical features were similar in both groups. Serum voltage-gated potassium channel (VGKC) antibodies were detected using a (125)I-alpha-dendrotoxin immunoprecipitation assay in 38% of group A and in 28% of group B. Autoimmune disease and other autoantibodies were present in both groups more frequently than would be expected by chance (59 and 28%, respectively)-particularly myasthenia gravis and acetylcholine receptor (AChR) antibodies. The neurological disorder in both groups could occur as a paraneoplastic condition. Thymoma was detected in 19 and 11%, respectively, and lung cancer in 10 and 6%, respectively. An axonal neuropathy was present in six (14%) of group A and in one (6%) of group B patients. Thus, despite the discrete EMG distinction, both groups share clinical features often associated with autoimmune-related diseases, which can occur as paraneoplastic disorders and, importantly, have an increased frequency of VGKC antibodies. We conclude that autoimmunity, and specifically VGKC antibodies in many cases, are strongly implicated in the pathogenesis of both groups, and that the EMG features reflect quantitative rather than qualitative differences between the diverse clinical syndromes. These findings also have relevance for disease management. A classification is proposed that distinguishes immune-mediated PNH (irrespective of whether VGKC antibodies are detectable by standard assays) from non-immune forms of PNH that include toxins, anterior horn cell degeneration in motor neurone disease and genetic disorders.

Age of Onset↗