Correspondence

Transient Improvement of Aphasia with Zolpidem

N Engl J Med 2004; 350:949-950February 26, 2004

Article

To the Editor:

There is currently no effective pharmacologic treatment for chronic aphasia, a frequent and incapacitating consequence of hemispheric stroke. We report the case of a 52-year-old right-handed woman, who had a stroke that affected her left insula, putamen, and superior temporal gyrus. Three years later, her speech was still restricted to stereotyped syllables, with not a single identifiable word. Language comprehension was better preserved. Because of occasional insomnia, zolpidem (10 mg) was prescribed. To the amazement of the patient and her family, ingestion of the first dose was followed by a dramatic improvement in her speech, which persisted until the patient went to bed later in the night. On the following morning, aphasia had returned at its usual level of severity. This phenomenon was systematically reproducible, reflecting a regular temporal pattern. About 20 minutes after the ingestion of zolpidem, the patient regained effective speech abilities, and zolpidem did not induce major sleepiness. She then engaged in meaningful, albeit telegraphic, speech, consisting of sentence fragments with accurately selected words. In contrast to her basal status, she could repeat most single words and pseudowords, and the first words of sentences; she was able to name most pictures of objects correctly and count up to 10.

An electroencephalogram showed slow waves over the left temporal region and did not change with ingestion of zolpidem. Single-photon-emission computed tomography with technetium-99m–labeled ethyl-cysteinate dimer showed an area of nonperfusion overlapping the lesion, with moderate hypoperfusion in contiguous frontal and parietal areas. Thirty minutes after the ingestion of zolpidem, an increase in regional cerebral blood flow of 35 to 40 percent was observed in Broca's area, in the left middle frontal and supramarginal gyri, and bilaterally in the orbitofrontal and mesial frontal cortex (Figure 1Figure 1Areas of Increased Regional Cerebral Blood Flow (Blue) after the Ingestion of Zolpidem, Shown by Single-Photon-Emission Computed Tomography and Superimposed on the Patient's Magnetic Resonance Images (Green).). The patient left France after the completion of these studies. No follow-up information is available.

Zolpidem is a benzodiazepine agonist selective for α₁ subunit–containing γ-aminobutyric acid (type A) receptors.1,2 Apart from its hypnotic properties, it markedly improves catatonia.3 In a patient with complete mutism and akinesia, treatment with zolpidem resulted in transient recovery of effective verbal and gestural interaction, effects that were concomitant with increased regional cerebral blood flow in left-hemispheric structures.4

Considering the complete stability of aphasia over a period of years and the increase in regional cerebral blood flow with zolpidem, it seems unlikely that the improvement of speech in our patient resulted from the suppression of a seizure. One may speculate that the lesion, possibly in the lentiform nucleus,5 impeded the operation of intact structures involved in language production, including Broca's area and the mesial frontal cortex. Zolpidem may transiently counteract this dynamic diaschisis, allowing for improved functioning of the residual language network. A selected subgroup of patients with aphasia, perhaps with subcortical lesions and spared but hypometabolic cortical structures, might benefit from this treatment.

Laurent Cohen, M.D., Ph.D.
Bassem Chaaban, M.D.
Marie-Odile Habert, M.D.
Hôpital de la Salpêtrière, 75651 Paris CEDEX 13, France

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   Stephanie C. Licata, Steven B. Lowen, George H. Trksak, Robert R. MacLean, Scott E. Lukas. (2011) Zolpidem reduces the blood oxygen level-dependent signal during visual system stimulation. Progress in Neuro-Psychopharmacology and Biological Psychiatry 35:7, 1645-1652
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   John Whyte, Robin Myers. (2009) Incidence of Clinically Significant Responses to Zolpidem Among Patients with Disorders of Consciousness. American Journal of Physical Medicine & Rehabilitation 88:5, 410-418
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   Sara I. Cohen, Thao T. Duong. (2008) Increased Arousal in a Patient with Anoxic Brain Injury After Administration of Zolpidem. American Journal of Physical Medicine & Rehabilitation 87:3, 229-231
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    W.-T. Wang, Y.-Y. Chen, S.-L. Wu, T.-S. Wei, S.-Y. Liu. (2007) Zolpidem dramatically improved motor and speech function in a patient with central pontine myelinolysis. European Journal of Neurology 14:10, e9-e10
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    Andrew Parton, Elizabeth Coulthard, Masud Husain. (2005) Neuropharmacological modulation of cognitive deficits after brain damage. Current Opinion in Neurology 18:6, 675-680
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