Hyperimmune goat serum for amyotrophic lateral sclerosis.

The authors report a patient with amyotrophic lateral sclerosis (ALS) who showed a lessening of deterioration in respiratory muscle strength during treatment with hyperimmune goat serum (HGS) (Aimspro). Respiratory function tests (RFTs) were measured by established protocols, and all measurements were expressed as a percentage of normal predicted values. The rate of decline was calculated by linear regression analysis. Respiratory muscle strength decline was less during 13 months of treatment with HGS (mean 1.3% per month, range 0.8-1.7%) compared to the preceding 13 months (mean 2.3% per month, range 1.2-3.1%), while a greater decline would be expected with disease progression. Comparison with similarly affected patients in the literature suggest that a decline of 4-5% per month of predicted values may be expected during the treatment phase.

WITHDRAWN: Goat serum product "Aimspro" restores conduction in demyelinated human optic nerve fibres.

Ahead of Print article withdrawn by publisher.

Hereditary motor and sensory neuropathy-russe: new autosomal recessive neuropathy in Balkan Gypsies.

A novel peripheral neuropathy of autosomal recessive inheritance has been identified in Balkan Gypsies and termed hereditary motor and sensory neuropathy-Russe (HMSN-R). We investigated 21 affected individuals from 10 families. Distal lower limb weakness began between the ages of 8 and 16 years, upper limb involvement beginning between 10 and 43 years, with an average of 22 years. This progressive disorder led to severe weakness of the lower limbs, generalized in the oldest subject (aged 57 years), and marked distal upper limb weakness. Prominent distal sensory loss involved all modalities, resulting in neuropathic joint degeneration in two instances. All patients showed foot deformity, and most showed hand deformity. Motor nerve conduction velocity was moderately reduced in the upper limbs but unobtainable in the legs. Sensory nerve action potentials were absent. There was loss of larger myelinated nerve fibers and profuse regenerative activity in the sural nerve. HMSN-R is a new form of autosomal recessive inherited HMSN caused by a single founder mutation in a 1 Mb interval on chromosome 10q.

A novel locus for autosomal recessive peripheral neuropathy in the EGR2 region on 10q23.

During our studies of Romany (Gypsy) families with hereditary motor and sensory neuropathy-Lom, we have identified a large kindred with two independently segregating autosomal recessive neuropathies. The novel disorder, named "hereditary motor and sensory neuropathy-Russe" (HMSNR), presented as a severe disabling form of Charcot-Marie-Tooth disease with prominent sensory loss, moderately reduced motor nerve conduction velocity, and a high threshold for electrical nerve stimulation. A genome scan in two branches of the large kindred detected linkage to the 10q22-q23 region containing the early growth response 2 gene (EGR2), a transcription factor with a key role in peripheral nerve myelination. The results of sequence analysis and the detection of an intragenic polymorphism allowed us to exclude EGR2 as the HMSNR gene. Further analysis done using linkage and recombination mapping refined the position of the HMSNR gene to a small interval on 10q23.2, flanked by markers D10S581 and D10S1742, telomeric to EGR2. In this interval, a conserved seven-marker haplotype is shared by all disease chromosomes, suggesting a single founder mutation. The homozygosity region is contained in bacterial-artificial-chromosome contig 1570 of the Sanger Centre physical map and has an estimated physical size of approximately 500 kb.

Congenital cataracts facial dysmorphism neuropathy syndrome, a novel complex genetic disease in Balkan Gypsies: clinical and electrophysiological observations.

During a study of hereditary motor and sensory neuropathy-Lom in Bulgaria, a previously unrecognized neurological disorder was encountered, mainly in Wallachian Gypsies, who represent a relatively recent genetic isolate. The disorder has been termed the congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome to emphasize its salient features. Fifty individuals from 19 extended pedigrees were identified and examined clinically and electrophysiologically. At least 1 patient from each family was admitted to the hospital in Sofia for full investigation. Pedigree analysis indicates autosomal recessive inheritance. The disorder is recognized in infancy by the presence of congenital cataracts and microcorneas. A predominantly motor neuropathy beginning in the lower limbs and later affecting the upper limbs develops during childhood and leads to severe disability by the third decade. Associated neurological features are a moderate nonprogressive cognitive deficit in most affected individuals together with pyramidal signs and mild chorea in some. Accompanying nonneurological features include short stature, characteristic facial dysmorphism, and hypogonadotrophic hypogonadism. Nerve conduction studies suggest a hypomyelinating/demyelinating neuropathy, confirmed by nerve biopsy. The CCFDN syndrome is thus a pleomorphic autosomal recessive disorder displaying a combination of neurological and nonneurological features.

Intercostal muscles in the rabbit: surgical anatomy and flap construction.

Demos and colleagues (1967) obtained good antireflux results from transposing an intercostal myoneurovascular pedicle around the gastro-oesophageal junction in dogs. An intact neurovascular supply is essential for the viability of a muscle flap. The aim of this study was to delineate the nerve and arterial supply to the left 11th intercostal muscle in the rabbit and to assess whether this muscle could be mobilized as a viable flap. The innervation of the muscle was studied using the methods of gross dissection in cadaveric specimens, and histological staining techniques. The arterial supply was studied using gross dissection, and aortography. In three non-recovery experiments, intercostal muscle was transposed around the gastro-oesophageal junction. The distal motor latency was recorded after electrical stimulation of the intercostal wraps. Gross dissection, histological staining techniques, and aortography showed that the left 11th intercostal muscle group in the rabbit is supplied by segmental vein, artery and nerve, running between external and internal intercostal muscles. Aortography and electrical stimulation demonstrated that the muscle group could be mobilized with an intact neurovascular supply. The left 11th intercostal muscle group has potential as a viable muscle flap for use in surgical procedures within the upper abdomen.

Correlation between varying levels of PMP22 expression and the degree of demyelination and reduction in nerve conduction velocity in transgenic mice.

Charcot-Marie-Tooth disease type 1A is most commonly caused by a duplication of a 1.5 Mb region of chromosome 17 which includes the peripheral myelin protein 22 gene (PMP22). Over-expression of this gene leads to a hypomyelinating/demyelinating neuropathy and to severely reduced nerve conduction velocity. Previous mouse and rat models have had relatively high levels of expression of the mouse or human PMP22 gene leading to severe demyelination. Here we describe five lines of transgenic mice carrying increasing copies of the human PMP22 gene (one to seven) and expressing increasing levels of the transgene. From histological and electrophysiological observations there appears to be a threshold below which expression of PMP22 has virtually no effect; below a ratio of human/mouse mRNA expression of approximately 0.8, little effect is observed. Between a ratio of 0.8 and 1.5, histological and nerve conduction velocity abnormalities are observed, but there are no behavioural signs of neuropathy. An expression ratio >1.5 leads to a severe neuropathy. A second observation concerns the histology of the different lines; the level of expression does not affect the type of demyelination, but influences the severity of involvement.

Mitochondrial DNA mutation underlying Leigh's syndrome: clinical, pathological, biochemical, and genetic studies of a patient presenting with progressive myoclonic epilepsy.

An 18-year-old male patient presented with clinical and radiological evidence of Leigh's syndrome (LS), having developed progressive myoclonic epilepsy and ataxia 11 years previously. Muscle biopsy showed cytochrome oxidase deficiency but no ragged red fibres. Autopsy confirmed the diagnosis of LS; there was additional degenerative change in the cerebellum and dentate and olivary nuclei, and an axonal peripheral neuropathy. Biochemical studies showed reduced activity of complexes I and IV of the respiratory chain in mitochondria from heart, liver and kidney. The mutation of mitochondrial DNA (mtDNA) at position 8344, commonly associated with the syndrome of myoclonic epilepsy and ragged red fibres, was detected in the patient's blood and was present in muscle, brain, liver, heart, and kidney in uniformly high amounts. It is clear that LS is genetically heterogeneous and represents one of the most severe phenotypes of a number of different mtDNA defects.

Magnetic resonance imaging of the optic nerve in extremes of gaze. Implications for the positioning of the globe for retrobulbar anaesthesia.

Orbital magnetic resonance imaging was carried out in nine directions of gaze in a normal subject. The findings are presented and discussed especially in relation to retrobulbar injections. Atkinson's position is confirmed to be hazardous and a new position for the globe at retrobulbar injections is suggested.

Acute optic neuritis. A cognitive and magnetic resonance imaging study.

Forty-two patients with acute optic neuritis (ON) (mean duration of symptoms 14.5 d) were compared with a matched, normal control group on a battery of tests of attention and information processing speed. Approximately half the sample (55%) had brain abnormalities shown by magnetic resonance imaging (MRI) and were more impaired across a variety of tests compared with those patients without brain lesions or normal controls. There was no difference in psychometric performance other than the pegboard task between the normal control group and those ON patients without brain involvement. Significant correlations were found between total lesion area in the brain and some tests of attention. Results from the Symbol Digit-Substitution Test were particularly sensitive in this regard and could correctly identify 70% of the sample with brain lesions.

Clinically isolated lesions of the type seen in multiple sclerosis: a cognitive, psychiatric, and MRI follow up study.

There is a dearth of longitudinal studies on psychometric and psychiatric change in multiple sclerosis (MS) particularly on the evolution of these abnormalities early in the disease process. A 4 1/2 year follow up study documenting magnetic resonance imaging (MRI), psychometric, and psychiatric abnormalities was undertaken in a group of 48 patients with clinically isolated lesions--for example, optic neuritis--which are frequently the harbinger of MS. At follow up about half the subjects had developed clinically definite MS, with memory deficits becoming apparent. Deficits in attention documented at initial assessment were present but unchanged in those subjects who still had a clinically isolated lesion status. However, after MS was categorised into a relapsing-remitting or chronic progressive course, patients with a chronic progressive course were found to have significantly deteriorated with regard to auditory attention tasks. T1 relaxation times in apparently normal white matter correlated with certain indices of cognitive impairment. In developing a model to explain the pathogenesis of intellectual and emotional change in MS, the interaction of organic, psychological, and social factors needs to be emphasised.

In vivo T1 values from guinea pig brain depend on body temperature.

T1 and T2 values were calculated from guinea pig brain in vivo at 0.5 T. T1 values showed significant dependence on body temperature, but the effect varied significantly from animal to animal and from one tissue type to another. Mean dependencies were 8.2 ms/degrees C for corpus callosum, 14.7 ms/degrees C for gray matter, and 21.5 ms/degrees C for hemispheric white matter (1.7, 2.6, and 4.5%/degrees C, respectively), all with respect to core temperature. These findings suggest that body temperature monitoring and control may be needed when sensitive measurements of T1 are being made. There was evidence for regulation of brain temperature within the hyperthermic range of body temperature.

MRI demonstration of midbrain deformity in association with Chiari malformation.

The differentiation of Chiari malformation from intrinsic brainstem neoplasm in adults can be difficult. We report three patients presenting with brainstem signs, in whom midbrain abnormality was detected on computed tomography and interpreted as evidence of intrinsic tumour. Subsequent investigation by magnetic resonance imaging revealed evidence of Chiari I malformation in all three cases and a syrinx in two. The association of Chiari I with deformity of the midbrain or pons has not been described previously.