Hyperekplexia and stiff-man syndrome: abnormal brainstem reflexes suggest a physiological relationship

Abstract

Background and objectives: Hyperekplexia and the stiff-man syndrome (SMS) are both conditions with exaggerated startle suggesting abnormal brainstem function. Investigation of brainstem reflexes may provide insight into disturbed reflex excitation and inhibition underlying these movement disorders. Patients and methods: Using four-channel EMG, we examined four trigeminal brainstem reflexes (monosynaptic masseter, masseter inhibitory, glabella, and orbicularis oculi blink reflexes) and their spread into pericranial muscles in five patients with familial hyperekplexia (FH), two with acquired hyperekplexia (AH), 10 with SMS, and 15 healthy control subjects. Results: Both FH/AH and SMS patients had abnormal propagation of brainstem reflexes into pericranial muscles. All patients with hyperekplexia showed an abnormal short-latency (15-20 ms) reflex in the trapezius muscle with a characteristic clinical appearance (''head retraction jerk'') evoked by tactile or electrical stimulation of the trigeminal nerve, but normal monosynaptic masseter reflexes. Inhibitory brainstem reflexes were attenuated in some FH/AH patients. Four of 10 patients with SMS had similar short-latency reflexes in the neck muscles and frequently showed widespread enhancement of other excitatory reflexes, reflex spasms, and attenuation of inhibitory brainstem reflexes. Conclusion: Reflex excitation is exaggerated and inhibition is attenuated in both stiff-man syndrome and familial or acquired hyperekplexia, indicating a physiological relationship. Reflex transmission in the brainstem appears biased towards excitation which may imply dysfunction of inhibitory glycinergic or GABAergic interneurons, or both.

Stiff-person syndrome: insights into a complex autoimmune disorder

“…Little or no response to visual and vestibular stimuli was recorded 72. Further evidence of altered supraspinal-inhibitory mechanisms has been reported with brainstem reflexes frequently showing increased excitation with hyper-synchronisation of multiple muscles, decreased inhibition and short-response latencies with a pattern similar to that observed in patients with hyperekplexia 73. An enhanced recovery cycle in the late (R2) component of the blink reflex is another feature of brainstem hyperexcitability in patients with SPS 74…”

Glutamic Acid Decarboxylase Autoimmunity With Brainstem, Extrapyramidal, and Spinal Cord Dysfunction

“…18 A study of trigeminal brainstem reflexes in patients with SMS suggested primary dysfunction of the inhibitory interneurons at the brainstem level. 19 In contemporary practice, neurologists generally reserve GAD65 antibody testing for patients who present with SMS, idiopathic cerebellar ataxia, or juvenile epilepsy. The fact that GAD65 antibody testing was not requested by the clinician for any patient in our study supports this practice.…”

Increased Muscle Tone as a Cause of Muscle Pain

“…The term "stiffman" is a misnomer, since women have long been recognized to be equally affected (Editorial 1967). Abnormally increased brain stem excitability and reflexes with exaggerated startle have been reported to occur in this condition (Molloy et al 2002;Khasani et al 2004). Abnormally increased brain stem excitability and reflexes with exaggerated startle have been reported to occur in this condition (Molloy et al 2002;Khasani et al 2004).…”

“…Stiff-person syndrome is of spinal or brainstem origin (Molloy et al 2002;Khasani et al 2004) and shows evidence of being an autoimmune disease (McEvoy 1991;Layzer 1994;Vogels et al 2003). The standard treatment for this condition has been benzodiazepines (McEvoy 1991).…”