Correspondence

Transient Improvement of Spinocerebellar Ataxia with Zolpidem

N Engl J Med 2004; 351:511-512July 29, 2004

Article

To the Editor:

There is currently no effective pharmacologic treatment for spinocerebellar ataxia. We describe a family of five patients, four of whom had clinical improvement within one hour after the ingestion of zolpidem (10 mg). The diagnosis of spinocerebellar ataxia type 2 was confirmed by molecular analysis. Analysis of DNA for CAG repeat expansions in the SCA1, 2, 3, 6, and 7 genes revealed expansion of CAG repeats at the SCA2 locus.

Patient 1, a 49-year-old man with titubation, dizziness, and loss of balance from the age of 34 years, had deteriorating speech and handwriting. Cerebellar signs included moderate gait ataxia, intention tremor, and dysdiadochokinesis, as well as titubation. Deep-tendon reflexes were all brisk. After treatment with zolpidem, ataxia, intention tremor, and titubation improved moderately.

Patient 2, a 37-year-old man with loss of balance and deterioration of handwriting since the age of 25 years, had bilaterally brisk tendon reflexes, ataxia, intention tremor, dysdiadochokinesis, and titubation. After treatment with zolpidem, ataxia, intention tremor, and titubation improved.

Patient 3, a 45-year-old man with speech incoordination since the age of 30 years, had explosive speech and severe dysarthria. His handwriting and speech were deteriorating. Tendon reflexes were bilaterally brisk. He had titubation, intention tremor, dysdiadochokinesis, and gait ataxia. After treatment with zolpidem, ataxia, intention tremor, and titubation improved moderately.

Patient 4, a 22-year-old woman, had loss of balance starting at the age of 18 years, with subsequent speech deterioration and occasional titubation. She was clinically depressed, muted in emotion, and only responded to instructions. She had gait ataxia and intention tremor. There was no improvement after treatment with zolpidem.

Patient 5, a 24-year-old woman with leg weakness and loss of balance, had had speech deterioration since the age of 22 years. Cerebellar signs included ataxia, intention tremor, and dysdiadochokinesis with intermittent titubation. Treatment with zolpidem slightly improved ataxia, intention tremor, and titubation.

Brain imaging with the use of single-photon-emission computed tomography with technetium-99m–labeled exametazime showed subnormal tracer concentrations in either the vermis or a cerebellar hemisphere in all patients. The images in Patient 2 showed markedly decreased uptake in the left thalamus and cerebellum (Figure 1AFigure 1Brain Perfusion Images before and after Treatment with Zolpidem in Patient 2.) that normalized after treatment with zolpidem (Figure 1B).

Zolpidem is a nonbenzodiazepine that belongs to the imidazopyridine class and is chemically distinct from barbiturates, antihistamines, benzodiazepines, and cyclopyrrolones. It has a selectivity for stimulating gamma-aminobutyric acid function and is oxidized and hydroxylated by the liver to inactive metabolites, which are eliminated primarily through renal excretion.1 Zolpidem has been shown to markedly improve catatonia, mutism, and aphasia,2-4 with concurrent normalization of cerebral hypoperfusion after brain injury. The action of zolpidem on injured brain is most likely due to the reversal of the diaschisis phenomenon, and the drug may be useful for other brain disorders.5

Ralf Clauss, M.D.
Royal Surrey County Hospital, Guildford GU2 7XX, United Kingdom
claussrp@yahoo.com

Mike Sathekge, M.Med.
Medical University of Southern Africa, Pretoria 0204, South Africa

Wally Nel, M.B., Ch.B.
Pollock Park Family Practice, Springs 0084, South Africa

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Citing Articles (7)

Citing Articles

1. 1

   Susan L. Perlman. 2012. Treatment and management issues in ataxic diseases. , 635-654.
   CrossRef

2. 2

   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
   CrossRef

3. 3

   Tin-Lun Tsai, Chin-San Liu, Chien-Hsu Lai. (2011) Nationwide Population-Based Epidemiologic Study on Cerebellar Ataxia in Taiwan. European Neurology 66:4, 215-219
   CrossRef

4. 4

   Francesca Pistoia, Elisa Mura, Stefano Govoni, Massimo Fini, Marco Sarà. (2010) Awakenings and Awareness Recovery in Disorders of Consciousness. CNS Drugs 24:8, 625-638
   CrossRef

5. 5

   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
   CrossRef

6. 6

   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
   CrossRef

7. 7

   Christine Brefel-Courbon, Pierre Payoux, Fabierine Ory, Agnes Sommet, Tarik Slaoui, Gaelle Raboyeau, Beatrice Lemesle, Michele Puel, Jean-Louis Montastruc, Jean-Francois Demonet, Dominique Cardebat. (2007) Clinical and imaging evidence of zolpidem effect in hypoxic encephalopathy. Annals of Neurology 62:1, 102-105
   CrossRef