Pathologic examinations have been of little help in determining the essential sites of this unstable neuronal discharge because in most cases, the disease is diffuse. Nonetheless, the most restricted lesions associated with myoclonus are located in the cerebellum and rostral brainstem. Removal of the modulating influence of the cerebellum on the thalamocortical system of neurons has been postulated as a mechanism, but it is uncertain whether the disinhibited motor activity is then expressed through corticospinal or reticulospinal pathways. For example, pentylenetetrazol injections evoke myoclonus in animals, and the myoclonus persists despite transection of corticospinal and other descending tracts of the hemispheres and upper brainstem until the lower brainstem reticular structures are destroyed.
To some degree, everyone startles or jumps in reaction to a totally unanticipated, potentially threatening stimulus. This normal startle reflex is probably a protective reaction, being seen also in animals, and its purpose seemingly is to prepare the organism for escape. In most ways, startle cannot be separated from myoclonus except for its generalized nature and an obligatory evocation by various stimuli. Any stimulus—most often an auditory one but also a flash of light, a tap on the neck, back, or nose, or even the presence of someone behind the patient—can normally evince a sudden contraction of the orbicularis, neck, and spinal musculature and even the legs. However, in the abnormal startle response that occurs in the diseases discussed below, the contraction is of greater amplitude and is more widespread, with less tendency to habituate. There may even be a jump and occasionally an involuntary shout and fall to the ground. It is these characteristics that distinguish pathologic startle.
Aside from exaggerated forms of the normal startle reflex, the commonest isolated syndrome is so-called startle disease, referred to as hyperexplexia or hyperekplexia (Gastaut and Villeneuve). This is a familial disease (e.g., the “jumping Frenchmen of Maine,” and others, as described further on). The nature of the phenomenon displayed by the “jumping Frenchmen of Maine” has been disputed. The syndrome was described originally by James Beard in 1868 among small pockets of French-speaking lumberjacks in northern Maine. The subjects displayed a greatly exaggerated response to minimal stimuli, to which there was no adaptation. The reaction consisted of jumping, raising the arms, screaming, and flailing of limbs, sometimes with echolalia, echopraxia, and a forced obedience to commands, even if this entailed a risk of serious injury. A similar syndrome in Malaysia and Indonesia is known as latah and in Siberia as miryachit. This syndrome has been framed in psychologic terms as conditioned responses (Saint-Hilaire et al) or as culturally determined behavior (Simons). Possibly some of the complex secondary phenomena can be explained in this way, but the stereotyped onset with an uncontrollable startle and the familial occurrence attest to a biologic basis. The most common mutation is in the 1-subunit of the inhibitory glycine receptor GLRA1 (Shiang et al) but other glycine receptor–related genes have been implicated in other cases. As pointed out by Suhren and associates and by Kurczynski, the condition is transmitted in some families as an autosomal dominant trait. The subject has been reviewed by Wilkins and colleagues and by Ryan and associates.