posterior fossa in some Asian populations, or other genetic vari-
ability, are greater risk factors for HFS than hypertension. This
may in part explain the commonly held observation that HFS is
more common in Asians. It could also be that neurogenic hyper-
tension is an important etiologic factor in only a select group of
HFS patients who are genetically predisposed. Neurophysiologic
or genetic studies may be needed to identify this subset of
patients.
Acknowledgment
The authors thank the Departments of Neurology and Diagnostic Radiol-
ogy, Singapore General Hospital, for their invaluable assistance.
From the Departments of Neurology (Drs. Tan, Lo, Pavanni, Wong, and Lim
and S.Y. Lum and S.Y. Han), Diagnostic Radiology (Dr. Chan), and Clini-
cal Research (S.M.C. Fook-Chong), Singapore General Hospital, National
Neuroscience Institute; and Healthway Medical Group (Dr. Koh), Singapore.
Received April 24, 2002. Accepted in final form September 28, 2002.
Address correspondence and reprint requests to Dr. Eng-King Tan, Depart-
ment of Neurology, Singapore General Hospital, Outram Road, Singapore
169608, Republic of Singapore; e-mail: gnrtek@sgh.com.sg
Lithium-induced periodic
alternating nystagmus
Michael S. Lee, MD; and Simmons Lessell, MD
Lithium, a well-known cause of downbeat nystagmus, has been
implicated in several other ocular motor disorders.1 We report a
woman on long-term lithium therapy who developed periodic al-
ternating nystagmus (PAN).
Case report. A 61-year-old woman, who had taken up to 1 g of
lithium a day since bipolar affective disorder was diagnosed 16
years earlier, noticed “something wrong with her vision while
driving.” The symptom persisted, but she denied any other eye or
neurologic symptoms. The patient was hypothyroid and was on
levothyroxine and fluoxetine. Her family history was not
contributory.
At the time of neuro-ophthalmic consultation, 4 months after
the onset of the visual disturbance, her visual acuities were 20/20
in each eye. She had horizontal jerk nystagmus that beat in one
direction for approximately 90 seconds, gradually resolved, and
after 10 seconds jerk nystagmus in the opposite direction super-
vened for approximately 90 seconds. This cycle of periodic oscilla-
tions continued without interruption. Her eye movements were
otherwise normal, as were the rest of her neuro-ophthalmologic
and neurologic examinations.
MRI of the brain with gadolinium revealed no abnormalities.
Her serum lithium level was in the therapeutic range. Lithium
was discontinued, but the PAN remained unchanged for 3 months.
An escalating dose of baclofen was prescribed, and at 20 mg three
times a day her nystagmus was abolished.
Comment. PAN is an uncommon disorder in which there is
continuous, horizontal nystagmus in primary gaze that reverses
direction approximately every 60 to 90 seconds with a 5- to 10-
second intermission. PAN can be congenital or acquired from
Arnold-Chiari malformations, MS, cerebellar lesions, brainstem
strokes, head trauma, or visual loss. Acute intoxication with anti-
convulsants such as phenytoin and primidone/phenobarbital may
also cause PAN.1 Experimentally ablating the cerebellar nodulus
and uvula in monkeys has induced PAN in the dark.2
In our patient there was no evidence of any underlying neuro-
logic disorder, and we presume that the lithium, despite being in
the therapeutic range, was responsible for the PAN.3,4 Lithium can
cause several types of eye movement disorders, most commonly
downbeat nystagmus. It has also been reported to cause smooth
pursuit abnormalities, oculogyric crisis, horizontal gaze palsy, in-
ternuclear ophthalmoplegia, opsoclonus, saccadic dysmetria, and
gaze-evoked nystagmus.1,3-5 Lithium toxicity can also cause perma-
nent cerebellar damage via neuronal loss and gliosis.6
344 NEUROLOGY 60 January (2 of 2) 2003
Copyright © 2003 by AAN Enterprises, Inc.
References
1. Wang A, Jankovic J. Hemifacial spasm: clinical findings and treatment.
Muscle Nerve 1998;21:1740 –1747.
2. Jannetta PJ, Segal R, Wolfson SK Jr. Neurogenic hypertension: etiology
and surgical treatment. I. Observations in 53 patients. Ann Surg 1985;
201:391–398.
3. Defazio G, Berardelli A, Abbruzzese G, et al. Primary hemifacial spasm
and arterial hypertension: a multicenter case-control study. Neurology
2000;54:1198 –1200.
4. WHO, Hypertension Control. Reports of a WHO expert committee.
WHO Technical Report Series 862, Geneva, World Health Organisa-
tion, 1996.
5. Oliveira LD, Cardoso F, Vargas AP. Hemifacial spasm and arterial hy-
pertension. Mov Disord 1999;14:832– 835.
6. Tan EK, Jankovic J. Hemifacial spasm and hypertension: how strong is
the association? Mov Disord 2000;15:363–365. Letter.
7. Tan EK, Chan LL, Lim SH, Lim WE, Khoo JB, Tan KP. Role of magnetic
resonance imaging and magnetic resonance angiography in patients with
hemifacial spasm. Ann Acad Med Singapore 1999;2:169 –173.
One report did not find any instance of nystagmus in a review
of 13 patients with acute lithium intoxication.3 However, another
described 12 patients who developed downbeat nystagmus while
on long-term lithium treatment. Ten of their 12 patients had
lithium levels within the therapeutic range. Additionally, four of
their six patients who stopped or reduced their dosage of lithium
had persistence of their nystagmus.4 The report concluded that
the nystagmus may result from long-term lithium therapy rather
than acute toxicity. Another report described seven patients who
developed nystagmus while on lithium.5 Five had been treated for
several years with therapeutic lithium levels before the nystag-
mus developed.
While we cannot prove that the lithium treatment caused this
patient’s PAN, there is no alternative explanation for an acquired
ocular motor disturbance of this type. The persistence of nystag-
mus despite cessation of the drug has been noted in cases of
lithium-induced downbeat nystagmus.1,3-5 Cerebellar dysfunction
is thought to play a role in PAN,1,2 and lithium can cause damage
to cerebellar Purkinje cells.6
To our knowledge, lithium has not been reported to cause PAN.
Our observations in the current case suggest that the association
is plausible, and lithium should be considered in the differential
diagnosis of acquired PAN.
From the Cole Eye Institute (Dr. Lee), Cleveland Clinic Foundation, Cleve-
land, OH; and the Neuro-ophthalmology Unit (Dr. Lessell), Massachusetts
Eye and Ear Infirmary, Harvard Medical School, Boston, MA.
Supported by the Heed Foundation, Cleveland, OH (M.S.L.).
Received August 30, 2002. Accepted in final form October 4, 2002.
Address correspondence and reprint requests to Dr. Michael S. Lee, Cole Eye
Institute/i-32, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland,
OH 44195; e-mail: leem4@ccf.org
Copyright © 2003 by AAN Enterprises, Inc.
References
1. Leigh RJ, Zee DS. The neurology of eye movements, 3rd ed. New York:
Oxford University Press 1999;424 – 426.
2. Waespe W, Cohen B, Raphan T. Dynamic modification of the vestibulo-
ocular reflex by the nodulus and uvula. Science 1985;228:199 –202.
3. Donaldson IM, Cunningham J. Persisting neurologic sequelae of lithium
carbonate therapy. Arch Neurol 1983;40:747–751.
4. Halmagyi GM, Lessell I, Curthoys IS, Lessell S, Hoyt WF. Lithium
induced downbeat nystagmus. Am J Ophthalmol 1989;107:664 – 670.
5. Corbett JJ, Jacobson DM, Thompson HS, Hart MN, Albert DW. Down-
beating nystagmus and other ocular motor defects caused by lithium
toxicity. Neurology 1989;39:481– 487.
6. Schneider JA, Mirra SS. Neuropathologic correlates of persistent neuro-
logic deficit in lithium intoxication. Ann Neurol 1994;36:928 –931.
 Lithium-induced periodic alternating nystagmus
Michael S. Lee and Simmons Lessell
Neurology 2003;60;344
DOI 10.1212/01.WNL.0000042787.51461.D1

This information is current as of January 28, 2003

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References This article cites 5 articles, 2 of which you can access for free at:
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