The involvement of the nervous system follows a predictable and biphasic pattern (Fisher and Adams). It begins locally, with palatal paralysis (nasal voice, regurgitation, and dysphagia) between the 5th and 12th days of illness. At this time or shortly afterward, other cranial nerves (trigeminal, facial, vagus, and hypoglossal) may also be affected. Ciliary body paralysis with loss of accommodation and blurring of vision but with preserved light reaction usually appears in the second or third week (the opposite of the Argyll Robertson reaction). Rarely, the extraocular muscles are weakened. The cranial nerve signs may clear without further involvement of the nervous system, or a delayed sensorimotor polyneuropathy may develop between the fifth and eighth weeks of the disease. The latter varies in severity from a mild, predominantly distal polyneuropathy of the limbs to a rapidly evolving, ascending paralysis, like that of the Guillain-Barré syndrome; CSF findings are similar as well (acellular fluid with elevated protein). The neuropathic symptoms progress for a week or two, and if the patient does not succumb to respiratory paralysis or cardiac failure (cardiomyopathy), these conditions stabilize and then improve slowly and more or less completely.
The early oropharyngeal symptoms, the ciliary paralysis with relatively retained pupillary response to light, and subacute evolution of a delayed symmetrical sensorimotor peripheral neuropathy distinguish diphtheria from other forms of polyneuropathy. The long latency between the initial infection and the involvement of the nervous system has no clear explanation. In experimental animals, Waksman and colleagues demonstrated that the toxin reaches the Schwann cells in the most vascular parts of the peripheral nervous system within 24 to 48 h of infection but its metabolic effect on cell membranes extends over a period of weeks. The toxin produces demyelination in the proximal parts of spinal nerves, in dorsal root ganglia, and in spinal roots. The cardiac musculature and the conducting system of the heart undergo mild focal necrosis.
The source of diphtheritic infection may be extrafaucial—a penetrating wound, skin ulcer, or infection of the umbilicus in the neonate. The systemic and neurologic complications of faucial diphtheria can also be observed in the extrafaucial form of the disease (wound infection) after a similar latent period. It is probable, therefore, that the toxin reaches neural sites via the bloodstream; but in addition, some action is exerted locally, as evidenced by palatal paralysis in faucial cases and by initial weakness and sensory impairment in the neighborhood of the infected wound.
There is no specific treatment for the neurologic complications of diphtheria. It is generally agreed that the administration of antitoxin within 48 h of the earliest symptoms of the primary diphtheritic infection lessens the incidence and severity of the peripheral nerve complications. The polyneuropathy of diphtheria is discussed further in Chap. 43 (see also McDonald and Kocen).
Botulism is a rare form of food-borne illness caused by the exotoxin of Clostridium botulinum. Outbreaks of poisoning are most often caused by ingested bacteria contained in home-preserved than in commercially canned products, and vegetables and home-cured ham are incriminated more commonly than are other food products. Very rarely, a contaminated wound is the source of infection. Although the disease is ubiquitous, five western states (California, Washington, Colorado, New Mexico, and
Oregon) account for more than half of all reported outbreaks in the United States. Neonatal and infantile forms of the disease have been reported. These are a result of absorption of the toxin formed by germination of ingested spores (rather than ingestion of preformed toxin), an important source of which is contaminated natural (raw) honey. A few adult cases may have a similar source.