Rubral Tremor After
Thalamic Infarction
in Childhood
Hüseyin Tan, MD*, Güzide Turanli, MD†,
Hakan Ay, MD‡, and Isil Saatçi, MD§
The occurrence of tremor after thalamic lesions is well
known. Delayed rubral tremor secondary to bilateral
thalamic infarction is a rare finding and has not been
reported previously in childhood. We present two
children with a combined resting-postural-kinetic
tremor caused by bithalamic infarction. The first child
was a male 14 months of age, and the second was a
male 9 years of age. These children come from unrelated families. On hospital admission of the first patient, generalized seizures and routine electroencephalogram (EEG) findings with diffuse spike-wave
discharges predominantly over the left frontal area
were clinically observed, leading to the initial diagnosis
of epilepsia partialis continua. However, clinical observation and video-EEG monitoring of the movements
revealed nonepileptiform accompaniments, favoring
the diagnosis of rubral tremor. In the second patient,
EEG revealed no paroxysmal activity and was within
normal limits for age. In both patients, cranial magnetic resonance imaging revealed ischemic lesions in
thalami bilaterally but failed to reveal any mesencephalic lesion. These patients demonstrate that thalamic
infarction can cause rubral tremor in childhood.
© 2001 by Elsevier Science Inc. All rights reserved.

different idiopathic forms that are caused by brain trauma
or multiple sclerosis, are uncommon but often give rise to
severe disability [1]. The term “rubral tremor” (also called
Holmes’ tremor or midbrain tremor) is used to describe a
tremor that is revealed at rest and becomes pronounced on
goal-directed movement [2,3]. The appearance of tremor
after thalamic lesions is well known but infrequent [4,5].
A computer-based scanning of the National Library of
Medicine revealed that an association between medial
bithalamic infarction and isolated rubral tremor has not
been described previously, although thalamic infarction in
children (particularly in infancy) has occasionally been
reported [6,7]. Therefore we report two children with
isolated rubral tremor associated with thalamic infarction.
Case Reports
Patient 1

Tremor is the most common movement disorder. Most
patients with tremor have Parkinson’s disease or essential
tremor. The remaining types of tremor, consisting of

A male patient 14 months of age was admitted to the hospital because
of high fever and restlessness. He had a 1-year history of Wilms’ tumor,
for which a right nephrectomy had been performed 9 months previously.
Follow-up abdominal ultrasound scan 3 months postoperatively revealed
a left renal mass, 1-2 cm in size. The patient underwent a course of
chemotherapy, receiving the last dose 1 week before admission.
On admission, the patient was febrile with a temperature of 39.2°C.
His pulse was 72/minute, and respiratory rate was 32/minute. Neurologic
and physical examinations were otherwise normal. Hematologic and
blood chemistry values were in normal limits except for a marked
neutropenia (2000 WBC/mm3). An extensive microbiologic analysis,
including culture and microscopic examinations of blood, urine, and
cerebrospinal fluid, failed to reveal any source of infection. The patient
responded well to antibiotic treatment.
On the third day of admission, a low-amplitude resting tremor in all
limbs was observed. The tremor was more apparent in the distal parts of
the upper limbs and the amplitude increased on attempts to reach a target.
The following day, additional involuntary movements on the right side of
the body, predominantly in the face, neck, and arm, appeared. The
amplitude of these 3-Hz clonic movements increased progressively and
resulted in abduction and adduction of the right arm at the shoulder joint
in the resting position. Neurologic examination revealed synchronous,
low-amplitude involuntary movements involving the tongue and the
proximal right lower extremity muscles. The movements tended to
disappear during sleep, and increased in amplitude on awakening and in
response to verbal, tactile, and noxious stimuli.
Phenobarbital therapy (5 mg/kg/day) was introduced on the sixth day
of admission after two successive afebrile generalized seizures recorded
at the time of the abnormal movements. While the movements continued,
eight-channel electroencephalogram (EEG) recording revealed bilateral
synchronous 3.5-4-Hz spike-and-wave discharges of higher amplitude in
the left frontal area. Three-hour video-EEG monitoring revealed the same
localized abnormality. A causal relationship between these EEG abnormalities and the tremor-like movements was difficult to establish.

From the *Department of Pediatrics, Atatürk University Faculty of
Medicine, Ankara, Turkey; and the †Department of Pediatric
Neurology, the ‡Department of Neurology, and the §Department of
Radiology, Hacettepe University Faculty of Medicine, Ankara, Turkey

Communications should be addressed to:
Dr. Tan; Hacettepe Üniversitesi; Pediatrik Nöroloji Bölümü; 06100
Sihhiye; Ankara, Turkey.
Received January 22, 2001; accepted June 22, 2001.

Tan H, Turanli G, Ay H, Saatçi I. Rubral tremor after
thalamic infarction in childhood. Pediatr Neurol 2001;25:
409-412.

Introduction

© 2001 by Elsevier Science Inc. All rights reserved.
PII S0887-8994(01)00331-9 ● 0887-8994/01/$—see front matter

Tan et al: Rubral Tremor in Childhood 409

Figure 1. (A) T2-weighted axial image
(TR/TE ⫽ 3,000/80 ms) indicating hyperintense lesions in the thalami bilaterally,
representing ischemic lesions (arrows).
Observe the atrophy with enlarged subarachnoid space and the ventricles. (B)
T2-weighted axial image (TR/TE ⫽
3,000/80 ms) of the 6-month follow-up
MRI revealing right thalamic chronic infarct with central cystic change (white
arrow). Also, observe the small left thalamic lesion (black arrow), possibly ischemic in origin.

Diazepam infusion during EEG monitoring obliterated completely the
spike-wave discharges, although the amplitude of persisting involuntary
movements remained the same. We were not able to perform a combined
EEG-electromyelogram (EMG) registration to demonstrate the possibility of a fixed temporal relationship between the tremor and EEG activity.
We concluded that the paroxysmal activity was not related to tremors,
because the tremors persisted after suppression of discharges with
diazepam. Although computed tomography (CT) of the brain was
normal, cranial magnetic resonance imaging (MRI) examination revealed
bilateral, symmetric, poorly defined lesions in the medial aspects of the
thalami, hyperintense on T2- and isointense on T1-weighted images, with
no mass effect or apparent contrast enhancement. The involuntary
movements did not improve with phenytoin (5 mg/kg/day) and clonazepam (0.01 mg/kg/day) treatment, and both drugs were discontinued.
Treatment then changed to valproic acid (20 mg/kg) and benztropine
(0.05 mg/kg), with marked improvement in both involuntary movements
and EEG abnormalities within few days. One month after discharge,
neurologic examination indicated no evidence of tremor. Repeat MRI
revealed that the thalamic lesions were more well defined (Fig 1A).

Patient 2
A male 9 years of age, whose family history was unremarkable, was
admitted to our hospital. Six months ago he developed sudden weakness
on his left side just after falling from an altitude of 2 meters, when, on
admittance to a different hospital, he was found to have left hemiparesis
and hemisensory loss. His weakness gradually improved, but 3 months
later he noticed the gradual onset of fine tremulous movement in his left
arm. This involuntary movement gradually worsened, and tremor appeared in his left leg.
On admission, his general condition was normal. Neurologic examination revealed him to be alert and oriented. Visual acuity was normal.
The other cranial nerves were intact. Deep tendon reflexes were symmetrically normal, and the plantar response was flexor bilaterally. His
gait was not ataxic. Apart from the tremor, the neurologic findings were
normal. Tremor of the left upper extremity was present principally during
sustained posture, becoming clear during intentional voluntary movements. The tremor subsided during sleep. Laboratory examination
findings were normal for blood cell count, acanthocytosis, red blood cell
morphology, routine serum chemistries, and erythrocyte sedimentation
rate, immunologic tests for autoimmune disorders, and urinalysis. Serum

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ceruloplasmin and copper levels were normal. Urine blood amino acid
profile, proteins C, S, and antithrombin III, blood homocysteine level,
C-reactive protein, and thyroid function tests were normal. Antinuclear
antibody, anti-DNA, antiphospholipid, and anticardiolipin antibodies,
and factor II and V Leiden mutations were negative. Electrocardiography
and echocardiography were both normal. We performed a video-EEG
test for the second patient, which was negative for a pathologic discharge
with a background activity consistent with his age. MRI revealed an
apparent right thalamic infarct with a minimal left thalamic involvement
(Fig 1B). No abnormality was present in the brainstem, cerebellum, or
basal ganglia. The selective cerebral angiogram did not reveal any
abnormality. Surface EMG indicated rhythmic grouping discharges of
approximately 4.5 Hz in the left forearm and hand at rest, and this was
rubral tremor frequency. The resting tremor component responded to
levodopa/carbidopa, whereas the kinetic component improved partially.

Discussion
Rubral tremor is a rare type of tremor, with 2-5-Hz
resting, postural, and kinetic components. Characteristically, it presents at rest, becomes more pronounced during
maintenance of a fixed posture and further increases in
amplitude with intentional voluntary movements [3,8].
The two patients described here demonstrated rubral
tremor as a manifestation of thalamic infarction confirmed
by MRI. Because extensive investigations toward the
etiology of cerebrovascular accident were negative, the
cause of lesion in the first patient was considered to be
nephroblastoma and chemotherapy. However, an acute
insult resulting from neutropenic fever could not be ruled
out. In the second case, the lesion was considered to be
caused by trauma. Stroke may develop in the course of
malignancies, especially those of solid tumors and lymphomas, and even the first symptom of either may be
stroke. The pathophysiology is considered to be the result
of low-grade disseminated intravascular coagulation and

secondary fibrinolysis, with the balance shifted toward
clotting. Chemotherapy is believed to cause stroke by
creating microangiopathy [9]. Trauma results in infarction
in the area of the basal ganglia by causing stretch in
perforating branches of middle cerebral artery [10]. The
tremor that was seen in our cases has many features of
rubral tremor, as described in the literature [11]. There is
no exact consensus regarding the definition of rubral
tremor. Some authors consider that this entity is actually a
cerebellar tremor associated with parkinsonian tremor [3].
The rest tremor component is considered to result from
involvement of the ascending nigrostriatal pathway,
whereas the kinetic component occurs in lesions involving
dentatorubrothalamic fibers [12].
The “Guillain-Mollaret triangle,” considered to be responsible for occurrence of rubral tremor, consists of three
corners, namely the red nucleus, inferior olivary nucleus
(via the central tegmental tract), and contralateral dentate
nucleus [13]. The so-called rubral, or midbrain, tremor is
primarily caused by red nuclear lesions, however, red
nucleus involvement is not necessary for its development
[14]. It is caused by a combination of damage to the
brachium conjunctivum and nigrostriatal pathways in the
vicinity of the red nucleus [7]. Vascular insults involving
medial or posterior regions of the thalamus, thalamosubthalamic area, and mesencephalon have also been reported
to be associated with rubral tremor [15].
The delay in onset has been reported as the most
striking feature of rubral tremor. Although varying, the
time interval between the date of the lesion and the
appearance of tremor usually ranges from 2 weeks to 2
years [16]. Although the date of the lesion was not known
in our first patient, the MRI findings were in favor of
chronic infarction. Regarding the second patient, tremor
typically arose clinically 3 months after the trauma.
Although the reason for this delay is not known precisely,
the proposed mechanism is the reorganization process
after deafferentation [17].
In both patients, lesions were demonstrated to involve
the thalami bilaterally. However, the second patient had
contralateral clinical findings related to right thalamic
lesion with minimal left involvement. No abnormality was
present in the brainstem, cerebellum, or basal ganglia in
either of our patients. In a recent review of published
reports, Lee and Marsden [18] found no isolated tremor
among 62 patients with movement disorders caused by a
lesion in the thalamic or subthalamic region. There were
11 patients with 2-5-Hz resting, postural, and intention
tremors in addition to dystonia. Lesions were secondary to
stroke in approximately one-half of the cases. Ghika et al.
[19] reported three adult patients with rubral-like tremor
syndrome caused by thalamic infarction in the territory of
the posterior choroidal artery. They examined another 54
patients with thalamic infarcts of other territories and
found no abnormal movements. The impact of this specific
territory has also been supported by two other cases with
rubral tremor secondary to posteromedially located tha-

lamic hemorrhage. There was no disturbance of consciousness or other signs of midbrain damage characteristic of
this location at the time involuntary movements began.
This raised the possibility that the stroke might have
occurred days before the onset of the tremor [3].
Clinical confusion may occur regarding the differentiation of rubral tremor from epilepsia partialis continua.
Clonic-like movements at rest usually raise the suspicion
of an epileptic origin. Coexistence of generalized seizures
and lateralizing epileptiform activity in EEG may lead an
erroneous diagnosis of epilepsia partialis continua. In our
patient, the persistence of movements after EEG had
returned to normal background activity favored a rubral
tremor. Moreover, the presence of postural and kinetic
components, stimulus sensitivity, impersistence into sleep,
and clinical response to anticholinergic treatment were
atypical for epilepsia partialis continua [20].
In conclusion, these cases demonstrate that thalamic
infarction can be the cause of isolated rubral tremor in
infancy and childhood. The frequent occurrence of accompanying seizures caused by high susceptibility to metabolic alterations and the delay in onset of the tremor may
lead to clinical confusion in the diagnosis of rubral tremor.
Therefore, an extensive laboratory evaluation, such as
video-EEG monitoring and MRI, along with neurologic
examination, should be performed in all children suspected to have rubral tremor.

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