36 months observational clinical study of 38 adult Pompe disease patients under alglucosidase alfa enzyme replacement therapy.

OBJECTIVES: Glycogen storage disease type 2(GSD2)/Pompe disease is characterized by respiratory and skeletal muscle weakness and atrophy, resulting in functional disability and reduced life span. METHODS: We present an open-label, investigator-initiated observational study of alglucosidase alfa enzyme replacement therapy (ERT) in 38 adult-onset GSD2 patients (20 female, 18 male) with a mean age at disease onset of 36.2 ± 10.5 years. Mean delay between symptom onset and start of ERT was 14.5 ± 7.2 years. Assessments included serial Walton Gardner Medwin scale, arm function tests, timed 10-meter walk tests, 4- stair climb tests, modified Gowers' maneuvers, 6-minute walk test (6MWT), MRC sum score, forced vital capacities (FVC), creatine kinase (CK) levels, and SF-36 selfreporting questionnaires. All tests were performed at baseline and every 12 months for 36 months of ERT. RESULTS: In the 6MWT we found 21 patients able to walk at baseline a mean distance of 312 ± 165.5 m, improving to 344 ± 165.8 m after 12 months (p=0.006), remaining at 356.4 ± 155.9 m at 24 months (p=0.033), and declining to 325.6 ± 174.8 m after 36 months of ERT (p=0.49, n.s.). The mean FVC in 28 patients was 80.27 ± 14.08% of predicted normal at baseline, after 12 months 79.19 ± 13.09%, at 24 months 78.62 ± 16.55%, and 77.19 ± 18.05%after 36 months. Only mean CK levels were significantly decreased by 8.8% (p=0.041). All other tests were statistically nonsignificant changed. CONCLUSION: Our data denote a rather variable course of neuromuscular deficits in chronic adult-onset Pompe patients during 36 months of alglucosidase alfa ERT.

Changes in intracortical excitability after successful epilepsy surgery.

Interictal activity from epileptic foci may have remote effects as demonstrable by assessing brain perfusion, metabolism and excitability. So far, the effect of surgical removal of the epileptic focus on cortical networks has only rarely been addressed. This study aims at an assessment of changes in intracortical inhibition and excitability in patients undergoing successful epilepsy surgery. Twenty-two patients (12 females, 10 males, mean age 37.8 years) with identical pre- and postsurgical antiepileptic medication were investigated using focal transcranial magnetic stimulation. Motor thresholds (MT), contralateral cortical silent periods (CSP) and amplitudes of motor evoked potentials (MEP) using paired pulse paradigms were investigated both, at the focal and non-focal hemisphere before and at least 3 months after successful epilepsy surgery. The postsurgical mean MT when stimulating at the focal hemisphere was significantly higher than at the non-focal hemisphere (p=0.01). Postsurgically, the mean duration of the CSP at 120% and at 150% of MT of the non-focal hemisphere was significantly shorter than presurgically (p=0.04), and the mean MEP amplitude following paired-pulse stimulation with an interstimulus interval of 10 ms of the non-focal hemisphere was significantly lower than presurgically (p=0.03). In summary, both parameters representing inhibition and facilitation changed following epilepsy surgery; effects were statistically significant on the non-focal hemisphere. Transcranial magnetic stimulation thus gave evidence of remote effects of an epileptic focus and its surgical removal. Extended changes in excitability due to the presence or absence of an epileptic focus may be related to widespread functional impairments in patients with focal epilepsy.

Polysegmental innervation of the medial paraspinal lumbar muscles.

A retrospective analysis was performed in a nine month period of the electrophysiological data, imaging and clinical findings of patients with monoradicular disc herniation compressing either the L5 or the S1 nerve root. The primary purpose of the analysis was to determine the distribution of pathological spontaneous activity in the medial paraspinal muscles on electromyographic examination in monoradicular L5 and S1 nerve root compression syndromes. Anatomically, the medial paraspinal muscles receive their innervation from a single root while the iliocostalis muscles and the longissimus muscle are thought to be innervated by multiple nerve roots. In the analysis, in single nerve root lesion of the L5 or S1 nerve root, electromyography of the medial paraspinal muscles revealed pathological spontaneous activity one to three vertebrae cranial to the disc herniation with extension to the opposite side of the lesion. In conclusion, the medial paraspinal muscles might be thought to be innervated by one single nerve root on anatomical studies, electrophysiologically the extension of axonal lesion signs of one single lumbar nerve root is much broader. The widespread distribution of the L5 and S1 nerve root must be taken into consideration on electromyographic examination of the medial paraspinal muscles.

Cervical myelopathy caused by soft-tissue mass in diffuse idiopathic skeletal hyperostosis.

A rare case of cervical spinal cord compression in diffuse idiopathic skeletal hyperostosis (DISH or Forestier's Disease) caused by a craniocervical mass of soft-tissue is reported. The objective is to describe an uncommon mechanism of spinal cord compression in DISH. Three weeks after a cardiac infarction a 69-year-old man slowly developed spastic tetraparesis. Magnetic resonance tomography showed a craniocervical tumor compressing the spinal cord and a massive DISH of the cervical spine. An extended mass of yellowish amorphous material was removed from between the dura, the posterior odontoid process and the posterior aspect of vertebral body C2 reaching to the upper part of C3.The histologic appearance indicated connective tissue and cell-degenerated cartilaginous tissue. There was no inflammatory component and no evidence of neoplasia. No ossification of the posterior longitudinal ligament (OPLL) was found. After removal and craniocervical stabilization the patient's neurologic function improved remarkably. The increase of mechanical stress on the atlantoaxial segment and enhanced proliferation reaction of the connective tissue in DISH are suggested as the underlying pathomechanisms in the formation of this soft-tissue mass.

Dermatomyotomal supply in patients with variations in the number of lumbar vertebrae.

OBJECT: Variation in the number of lumbar vertebrae occurs in a small portion of the population. Either the fifth lumbar vertebra shows assimilation to the sacrum or the first sacral vertebra shows a lumbar configuration, resulting in 4 or 6 lumbar vertebrae, respectively. Etiologically, lumbar nerve root syndrome is diagnosed by comparing the anatomical level of the disc herniation to the compressed nerve root and to the pattern of the peripheral sensory and motor deficit. In case of a variation in the number of lumbar vertebrae, defining the lumbar nerve roots becomes difficult. Variations in the number of lumbar vertebrae make the landmarks (the twelfth rib and the first sacral vertebra) unreliable clues to define the nerve roots. The allocation of the clinically damaged segment to the spinal disorder seen in imaging studies is essential for differential diagnosis and spine surgery. METHODS: A retrospective study was conducted of clinical, electrophysiological, and imaging data among inpatients over a period of 21 months. Eight patients who had isolated monosegmental discogenic nerve root compression and a variation in the number of lumbar vertebrae were selected. RESULTS: Seven patients presented with 6 lumbar vertebrae, and 1 patient presented with 4 lumbar vertebrae and disc herniation on 1 of the 2 caudal levels. Compression of the second-to-last nerve root in patients with 6 lumbar vertebrae resulted either in clinical L-5 or S-1 syndrome, or a combination of both. Compression of the last caudal nerve root resulted in a clinical S-1 nerve root syndrome. CONCLUSIONS: The findings suggest that the dermatomyotomal supply of the lumbosacral nerve roots can vary in patients with a variation in the number of lumbar vertebrae, and a meticulous clinical, radiological, and electrophysiological examination is essential.

Muscle hypertrophy of the lower leg caused by L5 radiculopathy.

We report on a case with hypertrophy of the tibial muscles and to a lesser extent of the calf muscles preceded by a lumbar syndrome and sciatica. Lumbar myelography disclosed a discogenic compression of the L5 nerve root. Muscle biopsy of the peroneal muscles showed a marked type I fibre predominance and hypertrophy but no inflammatory infiltration. We consider the possibility that radiculopathy not only of the S1 nerve root but also of the L5 root can trigger hypertrophy of the musculature and must be taken into account of the differential diagnosis of unilateral focal hypertrophy of the lower leg.