Risperidone Related Unilateral Rubral Tremor in Manic Patient

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					                                                                                                  Risperidone-related rubral tremor
                                                                                                CASE REPORT

Risperidone - Related Unilateral Rubral Tremor in a Manic
Patient—A Case Report

                           1                 2             1
Yu-Chih Shen, Yi-Chyan Chen , Giia-Sheun Peng , Wei-Wen Lin

                                                                                                                 1            2
Department of Psychiatry, Buddhist Tzu Chi General Hospital, Hualian, Taiwan; Department of Psychiatry , Neurology ,
Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan

Rubral tremor is a rare movement disorder that occurs typically with midbrain damage. The main features of this tremor are its low
frequency, irregular rhythm, presence at rest, and acceleration during posture and active movement. Antipsychotic agent-induced
tremors are usually bilateral parkinsonian tremors. We found no previous reports of unilateral rubral tremor in the literature. A 23-
year old man had unilateral rubral tremors as a result of a midbrain lesion plus risperidone exposure for treatment of manic symptoms.
After we stopped the use of risperidone, the tremor became less apparent and then disappeared. This case highlights the importance
of being aware of this rare complication in susceptible patients receiving risperidone treatment. (Tzu Chi Med J 2005; 17:437-

Key words: rubral tremor, parkinsonian tremor, antipsychotic agents, risperidone

                                                                       pathic parkinsonism, including tremor, rigidity and
                    INTRODUCTION                                       bradykinesia. Drug-induced parkinsonian tremor is usu-
                                                                       ally bilateral and commonly occurs during the first 5 to
     Rubral tremor is a rare movement disorder that oc-                30 days of treatment. We found no reports of drug-in-
curs typically with midbrain damage. Its frequency usu-                duced unilateral rubral tremor in the literature. We re-
ally is 2-5 Hz and includes resting, postural and kinetic              port the first case of a manic patient with unilateral rubral
components. It becomes more pronounced with a fixed                    tremor related to a midbrain lesion plus risperidone
posture, and further increases in amplitude with inten-                exposure.
tional voluntary movement [1]. Some authorities believe
that it is actually a cerebellar postural tremor plus a par-
kinsonian tremor [1], and can be caused by multiple scle-                                   CASE REPORT
rosis (MS) [2], vascular insults [3], tumors [4], head
trauma [5], neuroleptic exposure [6], and toxoplasma                       This 23-year-old unmarried man was in good health
abscess [7].                                                           and had no history of a mood disturbance before this
     Currently, numerous atypical antipsychotic agents                 episode. He visited our outpatient clinic with symptoms
such as risperidone, olanzapine and quetiapine are ap-                 of depressed mood, loss of interest, insomnia, poor
proved for the treatment of acute manic episodes [8].                  appetite, severe psychomotor retardation, and occupa-
Patients on these dopamine receptor antagonists may                    tional function impairment for 2-3 weeks. Under the
experience all of the common motor symptoms of idio-                   impression of a major depressive episode, he received

Received: April 8, 2005, Revised: May 19, 2005, Accepted: June 22, 2005
Address reprint requests and correspondence to: Dr. Wei-Wen Lin, Department of Psychiatry, Tri-Service General Hospital,
325, Section 2, Cheng Kung Road, Taipei, Taiwan

Tzu Chi Med J 2005      17    No. 6                                                                                               QPT
Y. C. Shen, Y. C. Chen, G. S. Peng, et al

antidepressant treatment and supportive psychotherapy,            We discontinued risperidone and the tremor became
and his depressive symptoms gradually remitted.              less apparent and then disappeared. Another mood
Unfortunately, he experienced a manic episode which          stablilizer, carbamazepine, was added to control manic
fulfilled the criteria of the DSM-IV [5] after receiving     symptoms and disturbing behaviors. Treatment with the
psychiatric medical treatment for 3 months. We stopped       two mood stabilizers, valproic acid and carbamazepine,
the use of antidepressants for two weeks to rule out the     combined with behavior therapy, resulted in gradual
possibility of antidepressant-induced mania but the          improvement of his manic symptoms.
manic symptoms remained. We then admitted this pa-
tient to our psychiatric ward for further management.
     During hospitalization, the patient was treated with                        DISCUSSION
mood stabilizers, such as valproate and clonazepam and
behavioral therapy. The mood symptoms subsided                    To our knowledge, this is the first description of
gradually but disruptive behaviors were still present. We    unilateral rubral tremor as a result of midbrain lesion
then added an atypical antipsychotic, risperidone, for       plus risperidone exposure in treating a manic patient. It
further management. We titrated the daily dose of            appears that a therapeutic dose of risperidone can lead
risperidone from 2 mg to 4 mg in 3 days. On the 4 th day     to rubral tremor in susceptible patients. Taken together,
of risperidone use, there was a unilateral resting tremor    our case and a previous report [6] of risperidone-induced
over the right extremities at a frequency of 3-4 Hz which    rubral tremor in a patient with posttraumatic ataxia sug-
was accelerated during sustained posture and guided          gest that the therapeutic use of risperidone could lead to
movement. There was no tremor on the opposite limb.          rubral tremor in certain patients who have underlying
     We consulted a neurologist and the patient was          brain problems. However, our patient had only right-
evaluated under the impression of rubral tremor.             side extremity rubral tremor, which is different from the
Tremography of the right upper extremity revealed regu-      previous report. The unilateral rubral tremor may be re-
lar burst formation at a frequency of 3-4 Hz in either a     lated to his left-side midbrain lesion plus treatment with
synchronous or alternative pattern with a particular         rieperidone.
posture. Brain magnetic resonance imaging (MRI) re-               Previous reports have indicated some risk factors
vealed increased signal density over the left cerebral       for development of rubral tremor and extrapyramidal
peduncle, left paramedian of the mid-brain (including        symptoms in patients receiving antipsychotic medica-
left red nucleus) and dorsal pons on T2-weighted             tion [6,9]. These factors include a past history of mood
imaging. Small bright lesions in the bilateral corona ra-    disorder or substance abuse, rapid dosage increase or a
diata were also noted which may have been related to         large total dose of the drug, advanced age, underlying
the midbrain abnormalities. The possible differential        brain problems and concurrent anti-dopaminergic
diagnosis included multiple sclerosis, encephalitis and      medications. Our patient had a mood disorder, rapid
other rare neurological illnesses. IgG synthesis of cere-    dosage increase and underlying brain lesions that might
brospinal fluid (CSF) rule out multiple sclerosis. On        have led to the development of unilateral rubral tremor
agarose gel electrophoresis of the CSF, no multiple bands    after risperidone treatment.
in the "slow" IgG region were found when compared                 The neural mechanisms underlying rubral tremor
with control CSF. Results of laboratory tests including      have been investigated in monkeys [10]. Three major
the erythrocyte sedimentation rate (ESR), C-reactive         neural elements in the ventromedial tegmental (VMT)
protein (CRP), rheumatoid factor (RF), antistreptolysin-     areas, the parvocellular division of the red nucleus, the
O (ASTO), rapid plasma regain (RPR), and human im-           cerebello-thalamic fibers passing through the red
munodeficiency virus (HIV) test ruled out encephalitis.      nucleus, and the nigrostriatal fibers have been found to
In addition, CSF studies such as aerobic and anaerobic       have interactions in producing tremors. In an animal
cultures, herpes simplex virus (HSV) 1 and 2, India ink      study, these three elements were destroyed stereotaxi-
for cryptococcus infection, acid - fast stain for tubercu-   cally from the VMT area either separately or in various
losis (TB) infection and fungus stain revealed no abnor-     combinations. When all three elements were destroyed,
mal findings. Other laboratory exams to rule out rare        rubral tremors appeared [10].
illnesses such as Wilson's disease, Hallervorden-Spatz            In our case, the development of unilateral rubral
syndrome and seizure disorders including plasma con-         tremor could have been due to lesions which destroyed
centrations of copper and ceruloplasmin, blood analysis      only the parvocellular division of the red nucleus and
for acanthocytes and evoked potentials also revealed no      cerebellothalamic fibers passing through the red nucleus
abnormal findings.                                           but spared thenigrostriatal fibers. The patient appeared

QPU                                                                                  Tzu Chi Med J 2005     17   No. 6
                                                                                        Risperidone-related rubral tremor

normal when not taking an antipsychotic agent. An an-          3. Tan H, Turanli G, Ay H, Saatci I: Rubral tremor after
tipsychotic agent, such as risperidone might have some            thalamic infarction in childhood. Pediatr Neurol 2001;
effects on the nigrostriatal fibers and cause dysfunction         25:409-412.
                                                               4. Leung GK, Fan YW, Ho SL: Rubral tremor associated
of all three elements. Rubral tremor developed in our             with cavernous angioma of the midbrain. Mov Disord
patient similar to those in the experiments in monkeys            1999; 14:191-193.
after the three elements were destroyed.                       5. Krack P, Deuschl G, Kaps M, Warnke P, Schneider S,
     In conclusion, we present the first case of unilateral       Traupe H: Delayed onset of "rubral tremor" 23 years
rubral tremor as a result of midbrain lesion plus                 after brainstem trauma. Mov Disord 1994; 9:240-242.
risperidone exposure in treating mania. This case high-        6. Friedman JH: "Rubral" tremor induced by a neuroleptic
lights the importance of being aware of rare complica-            drug. Mov Disord 1992; 7:281-282.
                                                               7. Pezzini A, Zavarise P, Palvarini L, Viale P, Oladeji O,
tions in susceptible patients receiving risperidone               Padovani A: Holmes' tremor following midbrain Toxo-
treatment.                                                        plasma abscess: Clinical features and treatment of a
                                                                  case. Parkinsonism Relat Disord 2002; 8:177-180.
                                                               8. Moreno RA, Moreno DH, Soares MB, Ratzke R:
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Tzu Chi Med J 2005     17   No. 6                                                                                     QPV

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