few days). The intrinsic muscle reflexes are diminished because of posterior root involvement, pyramidal tract signs are common, and mental abnormalities may be seen, ranging to dementia. The diagnosis rests on the demonstration of vitamin B12 deficiency. Vitamin B12 must be given as rapidly as possible, preferably by the intramuscular route.

Long tracts of the spinal cord can also be involved in paraneoplastic syndromes, tabes dorsalis due to neurosyphilis (pp. 116 f.), adrenoleukodystrophy (p. 122), and a number of congenital metabolic diseases.

Isolated diseases of the anterior horn cells are mostly of genetic (spinal muscular atrophies) or infectious origin (acute anterior poliomyelitis, p. 150). Amyotrophic lateral sclerosis, in which there is simultaneous degeneration of the anterior horn cells and the corticospinal and/or corticobulbar tracts, is usually sporadic.

The typical clinical features of diseases involving chronic loss of anterior horn cells are summarized in Table 7.3. Some of these diseases are described in further detail in this section.

Spinal Muscular Atrophies

These diseases are due to a genetic defect on chromosome 5 that causes isolated degeneration of the second (lower) motor neurons, i. e., the motor neurons of the anterior horn cells and the cranial nerve nuclei. The result is the typical clinical syndrome of anterior horn degeneration described above (flaccid weakness, muscle atrophy, loss of reflexes, fasciculations). The main clinical types of spinal muscular atrophy are classified according to their age of onset and the pattern of motor deficits that they cause:

In the early infantile type (Werdnig−Hoffmann), neonates and infants suffer from rapidly progressive muscle weakness, beginning in the muscles of the pelvic girdle. The affected children can survive for no more than a few years.

Amyotrophic Lateral Sclerosis (ALS)

This disease, also known as motor neuron disease (MND), is characterized by combined degeneration of the first and second motor neurons. Its clinical features are thus a combination of flaccid paresis, muscular atrophy, and spasticity.

Epidemiology. Three-quarters of patients are men, most of them between the ages of 40 and 65. More than 95 % of cases are sporadic; the rare familial cases are thought to be due to a defect of the Cu/Zn superoxide dismutase gene.

Neuropathological hallmark of this disease is loss of anterior horn cells, combined with degeneration of the pyramidal and corticobulbar tracts and of the Betz pyramidal cells of the precentral gyri.

Characteristic clinical manifestations are:

weakness and atrophy of the muscle groups of the limbs and trunk (including the respiratory apparatus) and/or the bulbar muscles (tongue, throat), progressing slowly over months,

fasciculations,

exaggerated reflexes,

(in some patients) pyramidal tract signs,

intact sensation,

often muscle cramps and pain.

Course. At first, there is circumscribed, asymmetrical, predominantly distal muscle atrophy, which is usually most obvious in the intrinsic muscles of the hands. There may be accompanying pain or fasciculations, which are often evident only on prolonged observation. As the disease progresses, muscle atrophy spreads proximally. Spasticity gradually appears as well; it is usually only mild at first and may indeed remain so over the ensuing course of the disease. The intrinsic muscle reflexes are usually brisk, more than one would expect in view of the concomitant atrophy and weakness, but py-

Fig. 7.14 Spinal muscular atrophy in a 46-year-old woman. There is marked atrophy of the muscles of the shoulder girdles, arms, and hands, as well as of the paravertebral musculature.

Fig. 7.15 Atrophy of the tongue due to true bulbar palsy in a 65- year-old woman with amyotrophic lateral sclerosis.

ramidal tract signs are not necessarily demonstrable. The bulbar muscles are also involved in about 20 % of patients, as manifested by atrophy, weakness, and fasciculations of the tongue (Fig. 7.15), dysarthria, and dysphagia (true bulbar palsy). Involvement of the corticobulbar tracts is indicated by exaggerated nasopalpebral, perioral and masseteric reflexes, and by involuntary laughter and crying, which are often present.

Treatment. Riluzole marginally slows the progression of the disease. There is no other specific treatment.

Prognosis. ALS takes a chronically progressive course. Death usually ensues within one or two years, although a minority of patients survives longer.

7

Diseases of the Spinal Cord