Martin S. Schwartz

What do we really know about amyotrophic lateral sclerosis

The cause of amyotrophic lateral sclerosis is unknown. In this review clinical and scientific data that are pertinent to understanding this disease are reviewed. There are currently several major controversies concerning the possible role of immunological factors, genetic factors, environmental toxins, and viral infection in pathogenesis. These concepts must be considered in relation to what is known about the disease in all its aspects, including epidemiological data, information on the classical and molecular pathology of the disease, and on associated involvement of other systems, e.g., the spinocerebellar pathways and frontal dementia. Only when all this information is assimilated can full understanding of the disease and, hopefully, a logical approach to treatment and prevention, be achieved.

The significance of ragged-red fibres in neuromuscular disease

The pathological significance of ragged-red fibres is uncertain. We have studied ragged-red fibres in the muscle biopsies of 3 adults; one with polymyositis and two with progressive external ophthalmoplegia. All the ragged-red fibres were Type 1 fibres. In two patients the mean diameter of the ragged-red fibres was significantly smaller than the unaffected Type 1 fibres. Some of these fibres showed features of regeneration, and others of degeneration. In the patient with polymyositis the mitochondria were proliferated and contained osmiophilic dense bodies; in the other two patients paracrystalline mitochondrial inclusions were prominent. These findings suggest that ragged-red fibres do not represent a single pathological process.

Pattern of segmental motor involvement in syringomyelia: a single fibre EMG study.

Single fibre EMG has been used to study the pattern of upper limb motor involvement in syringomyelia. Biceps brachii, extensor digitorum communis (EDC) and first dorsal interosseous muscles (1stDI) representing C5/6, C7/8 and C8/T1 segments, were studied. In the biceps the fibre density was slightly increased in most patients, in EDC it was about twice the normal and in the 1stDI it was about three times normal. The potentials were least stable and of longest duration in the 1stDI. These findings seem to indicate a relatively constant pattern of involvement of anterior horn cells in the brachial segments in syringomyelia.

Carbonic anhydrase III in neuromuscular disorders

Plasma carbonic anhydrase III (CAIII) and creatine kinase (CK) were measured in 44 patients with a variety of neuromuscular disorders. Markedly elevated CK levels were associated with similarly increased levels of CAIII. In 9 patients, only the CAIII was elevated, but in 2 patients only the CK was raised. The determination of plasma CAIII is thus an important index of muscle disorder and is probably more sensitive than CK.

Cancer-associated myasthenic (Eaton-Lambert) syndrome: distribution of abnormality and effect of treatment.

Treatment with plasma exchange, steroids, immunosuppressant drugs and cytotoxic chemotherapy was effective in two cases of cancer-associated Eaton-Lambert myasthenic syndrome. The clinical improvement noted during treatment was accompanied by improvement in the electrophysiological abnormality; this was much more marked in abductor digiti minimi and trapezius than in extensor digitorum brevis.

Neostigmine‐induced end‐plate proliferation in the rat A study using supra‐vital methylene blue

The supra-vital methylene blue technique was used to study motor end-plate morphology in 21 BD-1X rats, treated for 7 to 16 weeks with oral neostigmine bromide, and in five control animals. Motor endings of treated animals showed preterminal, terminal, and ultraterminal sprouting and an increase in mean end-plate length (p ≤ 0.001). These changes were most prominent after 14 weeks of treatment, After 16 weeks of therapy, mean end-plate length decreased and the proliferative abnormality became less evident. The adverse effect of neostigmine on motor end-plates may have clinical relevance in the management of myasthenia gravis and may be partly responsible for the end-plate abnormalities previously reported in this disease.

OSTEOMALACIC MYOPATHY: AN EXPERIMENTAL APPROACH

Osteomalacic myopathy: an experimental approach

The effect of continuous voluntary activation on neuromuscular transmission: A SFEMG study of myasthenia gravis and anterior horn cell disorders

In normal subjects the neuromuscular jitter does not increase during continuous voluntary activation. In patients with myasthenia gravis, spinal muscular atrophy and motor neurone disease we have found that the neuromuscular jitter may increase during recordings of several minutes of continuous voluntary activation at steady innervation rates. In some units this led to impulse blocking, and in other units an initially normal jitter increased beyond the normal range. Measurement of jitter during continuous voluntary activation at steady innervation rates provides relevant information in the evaluation of neuromuscular transmission and fatigue in these disorders.

Myasthenia Gravis and Other Myasthenic Syndromes

In this group of disorders transmission at the motor end-plates is abnormal. There are a number of possible abnormalities in motor endings which might result in inadequate neuromuscular transmission. These include abnormal synthesis of acetylcholine (ACh), defective release of ACh quanta, abnormalities in the neuromuscular cleft itself, abnormal post-synaptic ACh receptors and abnormal breakdown of ACh because of defective cholinesterase. However, although many of these possible sites of abnormality have been considered, at some time, in theories of the pathogenesis of the most common end-plate disorder, myasthenia gravis, abnormalities have been found only at some of these sites. In a number of congenital myasthenic syndromes discrete abnormalities in various components of the post-synaptic ACh receptor have been found, and in the Lambert—Eaton myasthenic syndrome release of ACh vesicles is abnormal (Table 12.1).

Classification of Neuromuscular Disorders

There are many different neuromuscular diseases and some are difficult to classify under a single heading. The World Federation of Neurology (1968) has proposed a classification, but many of the disorders included in their large list may not, in fact, be nosologically distinct, and others are very rare. We prefer a simpler classification which omits the rare disorders. None the less, some of them will be discussed in the relevant chapters. It should be noted that neurogenic disorders are generally classified according to the site of the major pathological process, for example anterior horn cell disorders are classified separately from neuropathies. Myopathies, on the other hand, are classified according to whether they are congenital or acquired, and those myopathies about which more is known, such as polymyositis, are classified separately. This difference in classification is due to the fact that in neurogenic disorders anterior horn cells, nerve roots, peripheral nerves with their myelin sheaths and the motor end-plates are vulnerable to different pathological processes whereas muscle itself is a more homogeneous tissue.