The startle syndromes: Physiology and treatment

Abstract

SUMMARYStartle syndromes are paroxysmal and show stimulus sensitivity, placing them in the differential diagnosis of epileptic seizures. Startle syndromes form a heterogeneous group of disorders with three categories: hyperekplexia (HPX), stimulus-induced disorders, and neuropsychiatric syndromes. HPX is characterized by an exaggerated motor startle reflex combined with stiffness and is caused by mutations in different parts of the inhibitory glycine receptor, leading to brainstem pathology. The preserved consciousness distinguishes it from epileptic seizures. Clonazepam is the first-choice therapy. The stimulusinduced disorders cover a broad range of epileptic and nonepileptic disorders, and distinguishing the two can be difficult. Additional information from electroencephalography (EEG) and video registration can help. Many stimulus-induced disorders now have an identified gene defect. Antiepileptic drugs, including benzodiazepines, are frequently mentioned as the best treatment option. Neuropsychiatric syndromes are on the borderland of neurology and psychiatry, and their etiology is poorly understood. These syndromes include startle-induced tics, culture-specific disorders such as Latah, and functional startle syndromes. The electromyography (EMG) startle reflex in these syndromes is characterized by variable recruitment patterns and the presence of a second ''orienting'' response. Treatment options are limited, but urgently required. In the clinical setting, the patient's history and a (home) video recording together with genetic and electrophysiologic testing help to classify these challenging disorders.

Correlating Structural and Energetic Changes in Glycine Receptor Activation

“…These perturbations give rise to impaired neurotransmission at glycinergic synapses, resulting in movement disorders such as hyperekplexia (6). Mutations in the ␣1 subunit have been most informative in this respect (7).…”

Presynaptic control of inhibitory neurotransmitter content in VIAAT containing synaptic vesicles

“…Disease symptoms subside in some patients as they age, presumably because GABAergic systems are eventually able to adapt and compensate for the deficiencies in glycine transmission. The most effective drug treatment for children born with hyperekplexia is benzodiazepines, which enhance existing GABAergic transmission (Dreissen and Tijssen, 2012;McAbee, 2015;Mineyko et al, 2011). Together these observations indicate that the circuits that are deficient in glycine also release GABA and have GABA receptors present but, like in GlyT2 knock-out animals, endogenous neonatal GABA systems are unable to compensate for a chronic loss of glycine signaling.…”

Narcolepsy: a clinical review

“…Hyperekplexia represents an exaggerated startle response, and is usually caused by mutations in inhibitory glycine receptor genes 16. It is associated with neonatal rigidity and generalised rigidity after startle; laughter does not precipitate this.…”