Thalamic Tumors in Childhood Clinical, Laboratory,
and
Genjiro Hirose, MD; Cesare
Lombroso, MD; Howard Eisenberg, MD
T.
Therapeutic
\s=b\ Eighteen cases of primary thalamic tumor occurring in children (ages 21/2 to 121/2 years) were studied retrospectively. Among the clinical features of this group that contrasted with adults having similar tumors were a shorter duration of symptoms before diagnosis and a higher incidence of motor abnormalities in the early illness. In several cases, symptoms and signs usually associated with cerebellar disorders predominated. Arteriography or gas encephalography or both were diagnostic in all but two cases. The electroencephalogram, abnormal in slightly more than 70% of the cases, suggested a thalamic mass in more than one third. A highly specific EEG feature was the presence of spindles while patients were awake. In 15 cases there was some evidence of ventricular dilation and nine of these later required shunts. In addition to shunting procedures, therapy included x-ray therapy alone or with craniotomy or craniotomy alone.
Considerations
cal observations at the onset of the illness with the autopsy findings. Thus, we have considered mainly the earliest clinical stages of the neoplastic disease when radiological and
other tests indicated it had not pro¬ gressed substantially beyond the gen¬ eral boundaries of the thalamus. Among the clinical features that characterized this group were the fol¬ lowing: a relatively short duration of symptoms, a high rate of occurrence of disorders of motor function, and increased intracranial pressure as part of the early illness. Frequently, disturbance of coordination, alone or in association with dysmetria, nys¬ tagmus, and hypoactive reflexes, sug¬ gested the presence of a cerebellar
Fig 1 .—Arterial phase of vertebral arteriogram made in patient with histologically veri¬ fied thalamic glioma. Posterior cerebral artery is shown by vertical arrow. Thalamo-perforating artery (angled arrow) and posterior choroidal artery (horizontal arrow) are elon¬ gated, displaced, and show distal dilation.
(Arch Neurol 32:740-744, 1975)
The published
series of cases of thalamic tumor include patients of all ages.1 "' Although in two of these reports'2 a study of age incidence re¬ vealed a relatively high frequency in childhood, and in another1 two appar¬ ent peaks, the first occurring within the first two decades, there has been no attempt, to our knowledge, to de¬ scribe the clinical course of this tumor in an exclusively pediatrie group. Eighteen children with primary thalamic tumors were treated at Chil¬ dren's Hospital Medical Center, Bos¬ ton, between 1962 and 1973. As is the case with tumor series, it is impos¬ sible to correlate accurately cliniAccepted for publication Dec 4,
1974. From the Seizure Unit and Division of Neurophysiology, departments of neurology and neurosurgery of Children's Hospital Medical Center and Harvard Medical School, Boston. Reprint requests to Children's Hospital Medical Center, 300 Longwood Ave, Boston, MA 02115 (Dr Lombroso).
Downloaded From: http://archneur.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/02/2015
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Fig 2.—Main features of EEG obtained on admission of 8-yearold girl with six-month history of headaches and two-week history of unsteady gait who had 2 diopters papilledema and was later found to have right-sided thalamic tumor. Note high-voltage bursts of bilateral theta and delta waves, with some more contin-
uous posterior irregular slowing, as often seen in children with obstructive hydrocephalus from infratentorial masses. Note also diffuse sigma-like rhythms, occurring while subject is awake and not receiving medication.
Fig 3—Electroencephalogram obtained on admission of 10year-old girl with six-month history of focal motor seizures and progressive gait disturbance who was found to harbor right-sided thalamic astrocytoma. Note nonlocalizable polymorphic delta
wave
activity over large areas of patient's right hemisphere where was depression of normal background rhythms. These were relatively well preserved over left hemisphere.
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sory disturbances were relatively uncom¬ mon. Two patients had paresthesia in an extremity. In one of these there was de¬ creased stereognosis in the same area. Three other patients had diminished sen¬ sation. Dysphasia, mainly a naming diffi¬ culty, was found in one right-handed pa¬ tient who had a tumor in the left side of the thalamus.
Diagnostic Studies Plain skull x-ray films, obtained in all were abnormal in six. In each case these abnormalities reflected in¬ creased intracranial pressure. Suture sepa¬ ration was seen in five cases, erosion of the sella in three, and increased digital mark¬ ing in one. Gas encephalography was used in 16 cases: in four of these the gas was in¬ troduced by the lumbar route and in 12 by ventricular puncture. The mass was demonstrated in 15 of these studies. In one case pneumoencephalography demon¬ strated mild ventricular dilation without deformity. Six years later a thalamic mass was shown by arteriography. Cerebral ar¬ teriography was done in 14 cases, and failed to demonstrate an abnormality in only one case. During the past several years, vertebral and carotid angiography has been done in all patients suspected of having a thalamic tumor. Stretching of the posterior choroidal arteries, bowing and hypertrophy of the thalamo-perforating arteries, and elevation of the thalamic vein have localized the mass in most of these cases (Fig 1). In 15 patients there was evi¬ dence of ventricular dilation as demon¬ strated by gas encephalography or arteri¬
patients, 50 >M
1 SEC
Fig 4.—Electroencephalogram from same recording illustrates sigma-like rhythms (akin to sleep spindles) occurring intermittently over frontal lobes while subject was awake with eyes open, and receiving no medications. disorder. The incidence of sensory ab¬ normalities was relatively low. PATIENTS The 18 children in this series ranged in age at the time of admission to the hospi¬ tal from 2 years 10 months to 12 years 7 months (median age of &k years). There were ten boys and eight girls. The diag¬ nosis of
a thalamic mass was made by pneumoencephalography, ventriculography, or cerebral angiography, or a combi¬ nation of these techniques. A histological diagnosis was made in 13 cases, and all
verified tumors
were
Symptoms
astrocytomas. and
Signs
The duration of symptoms from the on¬ set of the initial complaints to the time of admission varied considerably. The short¬ est period was one day in a boy 7 years 11 months old. Although he had bilateral pap¬ illedema on admission, the history failed to reveal symptoms other than a one-day his¬ tory of headache. Presumably, the longest duration was eight years in a girl, who had left focal and generalized seizures starting at age 2 years and who was found to have an astrocytoma in the right part of the thalamus. In another patient with neurofi¬ bromatosis and a two-year history of left
hemiplegia, diagnostic studies, including pneumoencephalography, failed to demon¬
strate a mass. Six years later, an arterio¬ gram, made because of progressive weak¬ ness, demonstrated the tumor. However, of the 18 patients, 15 had symptoms for less than six months before the diagnosis was made, and seven of these had them for less
than one month. The initial complaint in nine
patients
related to increased intracranial pres¬ sure, while in seven it was related to dis¬ orders of movement. Focal seizures that was
occasionally became generalized were the first symptoms in one patient, and the earliest complaint in another was pares¬ thesias of the left wrist. At the time of admission, disturbance of movement was the most common com¬ plaint, and only one patient had no symp¬ toms or signs of involvement of the motor system. Ten patients exhibited lateralized weakness frequently associated with hy¬ peractive deep tendon reflexes and an ex¬ tensor plantar response or both without weakness. Signs generally associated with cerebellar disorders were found in nine pa¬ tients and included the following: intention tremor, dysmetria, hypoactive deep tendon reflexes, ataxic gait, and titubation. In three of these patients there was no later¬ alized weakness, and these patients ini¬ tially appeared to have cerebellar mass le¬ sions. Involuntary movements, tremor, and choreoathetosis were seen in four patients. One patient had athetoid movements of the tongue. Symptoms of increased intracranial pressure, elicited in 13 patients, included headache frequently associated with vom¬ iting and lethargy (four patients). One pa¬ tient had enlarged head circumference (97%). Papilledema was seen in ten pa¬ tients, and bilateral sixth cranial nerve palsies in another. There were only three patients without symptoms or signs of in¬ creased pressure. Abnormalities of ex¬ traocular movements were present in six patients; five had nystagmus and one had limitation of upward gaze. Two patients had anisocoria. Visual field defects were detected in only two patients, both of whom had homonymous hemianopsia. Sen-
ography. Most patients had multiple EEGs during hospitalization, but only tracings obtained at admission were
are considered here. These classified into three groups: (1) EEGs
with preserved age, but with
background rhythms for predominantly unilateral hemispheral slowing without clearly focal lateralization; 12- to 14-hertz rhythms (akin to sleep spindles) were seen in some of these tracings while the subjects were awake; (2) EEGs with minimal or no preservation of normal background rhythms and with bilateral slowing; often higher voltage, bursts of diffuse theta and delta waves were seen in these tracings bilaterally; and (3) normal EEGs. A normal
tracing was obtained in two patients who had definite focal neurological deficits. Two other patients showed borderline EEG findings; these were also classified as normal. There were, then, four subjects with normal and 14 with abnormal EEGs on admission. Bilateral, diffuse slowing with some posterior predominance and
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bursts of slow waves, consistent with find¬ ings of raised intracranial pressure, were the main features in six subjects, all of whom had papilledema at the time the EEG was obtained (Fig 2). Eight other abnormal EEGs had more specific features. These included the following: ipsilateral depression or reduction of normal back¬ ground (alpha and theta rhythms) with preserved background contralaterally; bi¬ lateral, synchronous bursts of theta and delta waves; nonlocalized slowing in theta or delta range predominantly over one hemisphere. 12- to 14-Hz spindle-like activ¬ ities (sigma rhythms) ipsilaterally or con¬ tralaterally, while awake—a feature not previously described. Figures 3 and 4 illustrate these EEG features. Radioisotope scans were done in 12 patients. Six demonstrated a localized area of increased activity in the region of the thalamus; one scan was equivocal; five were normal. Two-dimensional ultrasonic scans were done in ten patients. Seven indicated the presence of a midline shift and three of these suggested the presence of tumor echoes; three were normal.
Pathological Findings A histological diagnosis was made in 13 of the 18 patients. In all cases the tumor was an astrocytoma, and seven were ma¬ lignant (greater than grade 2). Autopsies were performed in six cases, and in four of these the tumor had extended into the brain stem, in one as far caudally as the upper part of the pons. In one case tumor was found in the frontal and temporal lobes and in two cases the thalamus was involved bilaterally.
TREATMENT AND RESULTS
Treatment of this tumor in this series was not uniform and in most cases multiple modes of therapy were used. Operative management included needle biopsy (seven patients), crani¬ otomy with resection (11 patients), and cerebrospinal fluid shunting procedures (nine patients). Eleven patients were treated with x-ray therapy (4,500 to 5,100 rads), and intraventricularly given methotrexate was used in one case. Although the number of patients in each subgroup is obviously too small for meaningful comparisons, some useful observa¬ tions can be made. Of the seven patients who initially underwent needle biopsy, two suf¬ fered cerebral herniations with severe brain stem injury in the immediate postoperative period. Both had malig-
nant tumors. One died within 72 hours
of the operation. In the second case an emergency craniotomy with subtotal excision of the tumor was undertaken. Unfortunately, the patient remained in a decerebrate state and died six months later. Craniotomy and resec¬ tion of tumor was carried out in 11 cases. Five of these patients had prior needle biopsy. In four of these patients the decision to attempt resec¬ tion was made after permanent sections revealed a benign tumor. In nine cases the resection of tumor was recognized as subtotal. Two patients underwent multiple operations that resulted in what the surgeon believed was a grossly complete removal. These two cases deserve additional consider¬ ation. REPORT OF CASES Case 1.—A 6%-year-old girl with hemi¬ paresis and a visual field defect underwent a needle biopsy of a benign astrocytoma followed by a craniotomy and subtotal re¬ section in 1964. After the operation her hemiparesis was increased, but she other¬
wise did well until three years later when she returned to the hospital with increased intracranial pressure. Further resection of the tumor was done in two stages, one week apart. At the time of this report the patient is doing well. She has a residual hemiparesis, but is otherwise progressing normally and attending a regular school. Case 2.-In 1969 a boy 2 years 10 months old with hemiparesis underwent a crani¬ otomy with drainage of a cyst in the region of the thalamus. A small amount of tissue that was removed proved to be a benign astrocytoma. A ventriculoatrial shunt was made. A second craniotomy with resection of tumor was done six months later. Fol¬ lowing this operation, the hemiparesis im¬ proved. The patient has required revision of his shunt, but has done well. Presently, he has a spastic hemiparesis and a mild seizure disorder. Neither of these patients was given xray therapy. Of the remaining nine pa¬ tients treated with craniotomy, one is liv¬ ing, seven have died, and one has been lost to follow-up. Six of these patients received x-ray therapy. The surviving patient has been followed up for three years since the operation. The mean length of survival in those patients who have died was 15 months. One of these patients died in the immediate postoperative period. Five other patients were given x-ray therapy; one died 11 months after starting this therapy, three have survived for six, two,
and one years, respectively, and one is lost to follow-up. Of the entire group of 18 pa¬ tients, six are alive, ten have died, and two are lost to follow-up.
COMMENT
Primary tumors of the thalamus thought to account for approxi¬ mately 1% of intracranial neoplasms. Although they occur in all age groups, they appear less commonly in pa¬ are
'
tients older than 50 years.' The per¬ centage of these tumors that occur in childhood may be estimated by con¬ sidering the age incidence reported in three of the larger published series. Assuming that this is a represent¬ ative sample, the proportion of pa¬ tients 15 years old or younger is ap¬ proximately 25% (29 of 114 cases). In our series all of the patients at the time of admission to the hospital were younger than 13 years. The du¬ ration of symptoms from the time of onset until diagnosis has been re¬ ported to be usually short. Slightly more than 60% of the patients de¬ scribed by Tovi et al- and by McKissock and Paine' and Cheek and Taveras3 had symptoms for six months or less. The duration of symp¬ toms in the present series appears to be even shorter. The clinical manifes¬ tations in the present series were in some ways similar to those described in the reports reviewing patients of all age groups.1"' However, in our young patients, symptoms of motor abnormality seemed to occur more often, to occur earlier, and to be more intense, while in previous reports15 the most common symptoms at time of admission were related to in¬ creased intracranial pressure. Fur¬ thermore, at the time of admission signs usually associated with cerebel¬ lar lesions were often prominent, a feature not stressed in adult series.25 The patients in this study with cere¬ bellar syndromes without localizing neurological signs are of interest since they could have been suspected initially of having cerebellar tumors, the more common lesion in this age group. Although tremor is not uncom¬ monly associated with thalamic tu¬ mors, other adventitious movements are rarely seen.1-3 Millichap et al·3 re-
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-
ported two patients with this associa¬ tion, both of whom were children; one
had chorea and the other dystonic movements. It is interesting that in the present series four patients had involuntary movements. One patient in our series had dysnomia. Cheek and Taveras3 found dysphasia in 11 of their 51 patients. The association of speech disturbance with thalamic le¬ sion has been documented.7 The inci¬ dence of anisocoria in this study does not correspond with the findings of others.'3 This finding has generally been considered of diagnostic signifi¬ cance, the smaller pupil usually ipsi¬ lateral to the tumor. Only two pa¬ tients in our series had seizures prior to treatment. This is in contrast to the reports of others in which the in¬ cidence of seizures was approximate¬ ly 30%.2-3 Among the clinical features, then, that distinguish this group from those that included patients of all ages are an apparent shorter dura¬ tion of symptoms, a moderate in¬ crease in frequency, a greater degree of motor symptomatology in the early illness, and a greater incidence of involuntary movement disorders and especially of signs generally attrib¬ uted to cerebellar disease, while sei¬ zure manifestations were fewer. In cases studied histologically, the tumors were all of glial origin, being either astrocytomas or malignant astrocytomas. This corresponds to other studies that also revealed a high fre¬ quency of astrocytic tumors.14 Other tumors found in those reports were ependymoma, oligodendroglioma, and
ganglioma. We
aware of detailed EEG series of primarily thala¬ mic tumors. Cheek and Taveras3 briefly stated that abnormal EEGs were found in 90% of their cases; in 55% of these the EEG was of local¬ izing value, while in 10% false local¬ izing signs were reported. In our group of children, abnormal EEGs at admission were found in slightly more than 70% of the cases. About one half of these abnormal EEGs could be interpreted only as being consistent with a state of increased intracranial pressure, and correlated are
reports in
not a
well with the clinical picture at the time (Fig 2). The changes in these EEGs, mainly diffuse bursts of highvoltage theta/delta waves occurring in the waking state, have been re¬ ported in subjects with subtentorial tumors8 " and are generally attributed to the occurrence of acute obstructive hydrocephalus and the impinging by a dilated third ventricle on thalamic structures.9 In contrast to these
nonlocalizing signs found as the only abnor¬ mality in about one third (six) of all our subjects, over one third (eight) EEG
exhibited EEGs that could be consid¬ ered more specific for a mass lesion invading the thalamus. These EEGs included ipsilateral depression of nor¬ mal background rhythms, ipsilateral hemispheral polymorphic delta wave activity with no consistent focality, and sigma rhythms (akin to sleep spindles) occurring while patients were awake (Fig 3 and 4), with or without diffuse bursts of slow waves. Jasper and Van Buren10 reported that depression of ipsilateral alpha rhythms may be caused by lesions in¬ volving the mesial and anterior parts of the thalamus. Clinical cases de¬ scribed by Lam,11 Marshall and Walker,12 and Van der Drift and Magnus13 confirmed the depression of alpha activity on the side of le¬ sions destroying the anteromedial part of the thalamus. The latter au¬ thors also described diffuse poly¬ morphic delta rhythms arising ipsilat¬ erally to primary thalamic lesions. Similar findings were described by Hess11 in patients with lesions placed stereotactically in the thalamus. The
sigma rhythms sporadically appear¬ ing in some of these children when awake, and not previously described,
suggest involvement of thalamic structures also. The treatment of this lesion is gen¬
erally considered palliative. Arseni15 reported ten cases in which a thala¬ mic mass was thought grossly to have been totally removed. Not all of these lesions were neoplasms, and the oper¬ ative mortality in that series was 40%. Although the operative mortal¬ ity for craniotomy was only 10% in the present series, only one patient of
the nine who had known partial exci¬ sion is still living. Two other patients underwent what was believed by the operating surgeons to be total re¬ moval of benign tumors with good long-term results. In both cases this was done by another craniotomy when the patient experienced a new progression of symptoms after a pe¬ riod following a partial excision. In this series, as in others, needle biopsy of the tumor had a relatively high risk. Although it is obvious that this is much too small a series with which to study the benefits of x-ray therapy, in many recent cases we have used xray therapy and shunting procedures as necessary without biopsy as the initial mode of therapy. References 1. McKissock W, Paine KWE: Primary tumors of the thalamus. Brain 81:41-63, 1958. 2. Tovi D, Schisano G, Liljeqvist B: Primary tumors of the region of the thalamus. J Neurosurg 18:730-740, 1961. 3. Cheek WR, Taveras JM: Thalamic tumors. J Neurosurg 24:505-513, 1966. 4. Smyth GE, Stern K: Tumors of the thalamus: A clinicopathological study. Brain 61:339\x=req-\ 374, 1938. 5. Ody F: Tumors of the basal ganglia. Arch Neuro Psychiatry 27:249-269, 1932. 6. Millichap JG, Miller RH, Backus RC: Intracranial tumors in childhood. JAMA 179:589-593, 1962. 7. Ojemann GA, Ward AA, Jr: Speech representation in ventrolateral thalamus. Brain 94:669-680, 1971. 8. Daly D, Whelan JL, Bickford RG, et al: The electroencephalogram in cases of tumors of the posterior fossa and third ventricle. Electroencephalogr Clin Neurophysiol 5:203-215, 1953. 9. Martinius J, Matthes A, Lombroso CT: Electroencephalographic features in posterior fossa tumors in children. Electroencephalogr Clin Neurophysiol 25:128-139, 1968. 10. Jasper H, Van Buren JM: Interrelationship between cortex and subcortical structures: Clinical electroencephalographic studies. Electroencephalogr Clin Neurophysiol suppl 4, pp 168-188, 1953. 11. Lam RL: An unusual electroencephalogram associated with thalamic tumor. Electroencephalogr Clin Neurophysiol 2:329-330, 1950. 12. Marshall C, Walker AE: Electroencephalogram in thalamic hemorrhage. Electroencephalogr Clin Neurophysiol 2:99-102, 1950. 13. Van der Drift JHA, Magnus O: Primary thalamic lesions, in Magnus O, Van Lewen S, Cobb WA (eds): Electroencephalography and Cerebral Tumors. Amsterdam, Elsevier Publishing Co, 1961, pp 125-137. 14. Hess R: The influence of stereotactic lesions on the electroencephalogram, in Magnus O, Van Lewen S, Cobb WA (eds): Electroencephalography and Cerebral Tumors. Amsterdam, Elsevier Publishing Co, 1961, pp 166-171. 15. Arseni C: Tumors of the basal ganglia: Their surgical treatment. Arch Neurol Psychiatry 80:18-24, 1958.
Downloaded From: http://archneur.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/02/2015
and
Genjiro Hirose, MD; Cesare
Lombroso, MD; Howard Eisenberg, MD
T.
Therapeutic
\s=b\ Eighteen cases of primary thalamic tumor occurring in children (ages 21/2 to 121/2 years) were studied retrospectively. Among the clinical features of this group that contrasted with adults having similar tumors were a shorter duration of symptoms before diagnosis and a higher incidence of motor abnormalities in the early illness. In several cases, symptoms and signs usually associated with cerebellar disorders predominated. Arteriography or gas encephalography or both were diagnostic in all but two cases. The electroencephalogram, abnormal in slightly more than 70% of the cases, suggested a thalamic mass in more than one third. A highly specific EEG feature was the presence of spindles while patients were awake. In 15 cases there was some evidence of ventricular dilation and nine of these later required shunts. In addition to shunting procedures, therapy included x-ray therapy alone or with craniotomy or craniotomy alone.
Considerations
cal observations at the onset of the illness with the autopsy findings. Thus, we have considered mainly the earliest clinical stages of the neoplastic disease when radiological and
other tests indicated it had not pro¬ gressed substantially beyond the gen¬ eral boundaries of the thalamus. Among the clinical features that characterized this group were the fol¬ lowing: a relatively short duration of symptoms, a high rate of occurrence of disorders of motor function, and increased intracranial pressure as part of the early illness. Frequently, disturbance of coordination, alone or in association with dysmetria, nys¬ tagmus, and hypoactive reflexes, sug¬ gested the presence of a cerebellar
Fig 1 .—Arterial phase of vertebral arteriogram made in patient with histologically veri¬ fied thalamic glioma. Posterior cerebral artery is shown by vertical arrow. Thalamo-perforating artery (angled arrow) and posterior choroidal artery (horizontal arrow) are elon¬ gated, displaced, and show distal dilation.
(Arch Neurol 32:740-744, 1975)
The published
series of cases of thalamic tumor include patients of all ages.1 "' Although in two of these reports'2 a study of age incidence re¬ vealed a relatively high frequency in childhood, and in another1 two appar¬ ent peaks, the first occurring within the first two decades, there has been no attempt, to our knowledge, to de¬ scribe the clinical course of this tumor in an exclusively pediatrie group. Eighteen children with primary thalamic tumors were treated at Chil¬ dren's Hospital Medical Center, Bos¬ ton, between 1962 and 1973. As is the case with tumor series, it is impos¬ sible to correlate accurately cliniAccepted for publication Dec 4,
1974. From the Seizure Unit and Division of Neurophysiology, departments of neurology and neurosurgery of Children's Hospital Medical Center and Harvard Medical School, Boston. Reprint requests to Children's Hospital Medical Center, 300 Longwood Ave, Boston, MA 02115 (Dr Lombroso).
Downloaded From: http://archneur.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/02/2015
8.1 YEARS
F4-c4y^'^ Fp-F
50
µ
1SEC
sív* u JU.1 ü ff^fK^ji
3-0 ' " ,^^
/]/
Fig 2.—Main features of EEG obtained on admission of 8-yearold girl with six-month history of headaches and two-week history of unsteady gait who had 2 diopters papilledema and was later found to have right-sided thalamic tumor. Note high-voltage bursts of bilateral theta and delta waves, with some more contin-
uous posterior irregular slowing, as often seen in children with obstructive hydrocephalus from infratentorial masses. Note also diffuse sigma-like rhythms, occurring while subject is awake and not receiving medication.
Fig 3—Electroencephalogram obtained on admission of 10year-old girl with six-month history of focal motor seizures and progressive gait disturbance who was found to harbor right-sided thalamic astrocytoma. Note nonlocalizable polymorphic delta
wave
activity over large areas of patient's right hemisphere where was depression of normal background rhythms. These were relatively well preserved over left hemisphere.
there
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1SEC
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10.2 YEARS
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sory disturbances were relatively uncom¬ mon. Two patients had paresthesia in an extremity. In one of these there was de¬ creased stereognosis in the same area. Three other patients had diminished sen¬ sation. Dysphasia, mainly a naming diffi¬ culty, was found in one right-handed pa¬ tient who had a tumor in the left side of the thalamus.
Diagnostic Studies Plain skull x-ray films, obtained in all were abnormal in six. In each case these abnormalities reflected in¬ creased intracranial pressure. Suture sepa¬ ration was seen in five cases, erosion of the sella in three, and increased digital mark¬ ing in one. Gas encephalography was used in 16 cases: in four of these the gas was in¬ troduced by the lumbar route and in 12 by ventricular puncture. The mass was demonstrated in 15 of these studies. In one case pneumoencephalography demon¬ strated mild ventricular dilation without deformity. Six years later a thalamic mass was shown by arteriography. Cerebral ar¬ teriography was done in 14 cases, and failed to demonstrate an abnormality in only one case. During the past several years, vertebral and carotid angiography has been done in all patients suspected of having a thalamic tumor. Stretching of the posterior choroidal arteries, bowing and hypertrophy of the thalamo-perforating arteries, and elevation of the thalamic vein have localized the mass in most of these cases (Fig 1). In 15 patients there was evi¬ dence of ventricular dilation as demon¬ strated by gas encephalography or arteri¬
patients, 50 >M
1 SEC
Fig 4.—Electroencephalogram from same recording illustrates sigma-like rhythms (akin to sleep spindles) occurring intermittently over frontal lobes while subject was awake with eyes open, and receiving no medications. disorder. The incidence of sensory ab¬ normalities was relatively low. PATIENTS The 18 children in this series ranged in age at the time of admission to the hospi¬ tal from 2 years 10 months to 12 years 7 months (median age of &k years). There were ten boys and eight girls. The diag¬ nosis of
a thalamic mass was made by pneumoencephalography, ventriculography, or cerebral angiography, or a combi¬ nation of these techniques. A histological diagnosis was made in 13 cases, and all
verified tumors
were
Symptoms
astrocytomas. and
Signs
The duration of symptoms from the on¬ set of the initial complaints to the time of admission varied considerably. The short¬ est period was one day in a boy 7 years 11 months old. Although he had bilateral pap¬ illedema on admission, the history failed to reveal symptoms other than a one-day his¬ tory of headache. Presumably, the longest duration was eight years in a girl, who had left focal and generalized seizures starting at age 2 years and who was found to have an astrocytoma in the right part of the thalamus. In another patient with neurofi¬ bromatosis and a two-year history of left
hemiplegia, diagnostic studies, including pneumoencephalography, failed to demon¬
strate a mass. Six years later, an arterio¬ gram, made because of progressive weak¬ ness, demonstrated the tumor. However, of the 18 patients, 15 had symptoms for less than six months before the diagnosis was made, and seven of these had them for less
than one month. The initial complaint in nine
patients
related to increased intracranial pres¬ sure, while in seven it was related to dis¬ orders of movement. Focal seizures that was
occasionally became generalized were the first symptoms in one patient, and the earliest complaint in another was pares¬ thesias of the left wrist. At the time of admission, disturbance of movement was the most common com¬ plaint, and only one patient had no symp¬ toms or signs of involvement of the motor system. Ten patients exhibited lateralized weakness frequently associated with hy¬ peractive deep tendon reflexes and an ex¬ tensor plantar response or both without weakness. Signs generally associated with cerebellar disorders were found in nine pa¬ tients and included the following: intention tremor, dysmetria, hypoactive deep tendon reflexes, ataxic gait, and titubation. In three of these patients there was no later¬ alized weakness, and these patients ini¬ tially appeared to have cerebellar mass le¬ sions. Involuntary movements, tremor, and choreoathetosis were seen in four patients. One patient had athetoid movements of the tongue. Symptoms of increased intracranial pressure, elicited in 13 patients, included headache frequently associated with vom¬ iting and lethargy (four patients). One pa¬ tient had enlarged head circumference (97%). Papilledema was seen in ten pa¬ tients, and bilateral sixth cranial nerve palsies in another. There were only three patients without symptoms or signs of in¬ creased pressure. Abnormalities of ex¬ traocular movements were present in six patients; five had nystagmus and one had limitation of upward gaze. Two patients had anisocoria. Visual field defects were detected in only two patients, both of whom had homonymous hemianopsia. Sen-
ography. Most patients had multiple EEGs during hospitalization, but only tracings obtained at admission were
are considered here. These classified into three groups: (1) EEGs
with preserved age, but with
background rhythms for predominantly unilateral hemispheral slowing without clearly focal lateralization; 12- to 14-hertz rhythms (akin to sleep spindles) were seen in some of these tracings while the subjects were awake; (2) EEGs with minimal or no preservation of normal background rhythms and with bilateral slowing; often higher voltage, bursts of diffuse theta and delta waves were seen in these tracings bilaterally; and (3) normal EEGs. A normal
tracing was obtained in two patients who had definite focal neurological deficits. Two other patients showed borderline EEG findings; these were also classified as normal. There were, then, four subjects with normal and 14 with abnormal EEGs on admission. Bilateral, diffuse slowing with some posterior predominance and
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bursts of slow waves, consistent with find¬ ings of raised intracranial pressure, were the main features in six subjects, all of whom had papilledema at the time the EEG was obtained (Fig 2). Eight other abnormal EEGs had more specific features. These included the following: ipsilateral depression or reduction of normal back¬ ground (alpha and theta rhythms) with preserved background contralaterally; bi¬ lateral, synchronous bursts of theta and delta waves; nonlocalized slowing in theta or delta range predominantly over one hemisphere. 12- to 14-Hz spindle-like activ¬ ities (sigma rhythms) ipsilaterally or con¬ tralaterally, while awake—a feature not previously described. Figures 3 and 4 illustrate these EEG features. Radioisotope scans were done in 12 patients. Six demonstrated a localized area of increased activity in the region of the thalamus; one scan was equivocal; five were normal. Two-dimensional ultrasonic scans were done in ten patients. Seven indicated the presence of a midline shift and three of these suggested the presence of tumor echoes; three were normal.
Pathological Findings A histological diagnosis was made in 13 of the 18 patients. In all cases the tumor was an astrocytoma, and seven were ma¬ lignant (greater than grade 2). Autopsies were performed in six cases, and in four of these the tumor had extended into the brain stem, in one as far caudally as the upper part of the pons. In one case tumor was found in the frontal and temporal lobes and in two cases the thalamus was involved bilaterally.
TREATMENT AND RESULTS
Treatment of this tumor in this series was not uniform and in most cases multiple modes of therapy were used. Operative management included needle biopsy (seven patients), crani¬ otomy with resection (11 patients), and cerebrospinal fluid shunting procedures (nine patients). Eleven patients were treated with x-ray therapy (4,500 to 5,100 rads), and intraventricularly given methotrexate was used in one case. Although the number of patients in each subgroup is obviously too small for meaningful comparisons, some useful observa¬ tions can be made. Of the seven patients who initially underwent needle biopsy, two suf¬ fered cerebral herniations with severe brain stem injury in the immediate postoperative period. Both had malig-
nant tumors. One died within 72 hours
of the operation. In the second case an emergency craniotomy with subtotal excision of the tumor was undertaken. Unfortunately, the patient remained in a decerebrate state and died six months later. Craniotomy and resec¬ tion of tumor was carried out in 11 cases. Five of these patients had prior needle biopsy. In four of these patients the decision to attempt resec¬ tion was made after permanent sections revealed a benign tumor. In nine cases the resection of tumor was recognized as subtotal. Two patients underwent multiple operations that resulted in what the surgeon believed was a grossly complete removal. These two cases deserve additional consider¬ ation. REPORT OF CASES Case 1.—A 6%-year-old girl with hemi¬ paresis and a visual field defect underwent a needle biopsy of a benign astrocytoma followed by a craniotomy and subtotal re¬ section in 1964. After the operation her hemiparesis was increased, but she other¬
wise did well until three years later when she returned to the hospital with increased intracranial pressure. Further resection of the tumor was done in two stages, one week apart. At the time of this report the patient is doing well. She has a residual hemiparesis, but is otherwise progressing normally and attending a regular school. Case 2.-In 1969 a boy 2 years 10 months old with hemiparesis underwent a crani¬ otomy with drainage of a cyst in the region of the thalamus. A small amount of tissue that was removed proved to be a benign astrocytoma. A ventriculoatrial shunt was made. A second craniotomy with resection of tumor was done six months later. Fol¬ lowing this operation, the hemiparesis im¬ proved. The patient has required revision of his shunt, but has done well. Presently, he has a spastic hemiparesis and a mild seizure disorder. Neither of these patients was given xray therapy. Of the remaining nine pa¬ tients treated with craniotomy, one is liv¬ ing, seven have died, and one has been lost to follow-up. Six of these patients received x-ray therapy. The surviving patient has been followed up for three years since the operation. The mean length of survival in those patients who have died was 15 months. One of these patients died in the immediate postoperative period. Five other patients were given x-ray therapy; one died 11 months after starting this therapy, three have survived for six, two,
and one years, respectively, and one is lost to follow-up. Of the entire group of 18 pa¬ tients, six are alive, ten have died, and two are lost to follow-up.
COMMENT
Primary tumors of the thalamus thought to account for approxi¬ mately 1% of intracranial neoplasms. Although they occur in all age groups, they appear less commonly in pa¬ are
'
tients older than 50 years.' The per¬ centage of these tumors that occur in childhood may be estimated by con¬ sidering the age incidence reported in three of the larger published series. Assuming that this is a represent¬ ative sample, the proportion of pa¬ tients 15 years old or younger is ap¬ proximately 25% (29 of 114 cases). In our series all of the patients at the time of admission to the hospital were younger than 13 years. The du¬ ration of symptoms from the time of onset until diagnosis has been re¬ ported to be usually short. Slightly more than 60% of the patients de¬ scribed by Tovi et al- and by McKissock and Paine' and Cheek and Taveras3 had symptoms for six months or less. The duration of symp¬ toms in the present series appears to be even shorter. The clinical manifes¬ tations in the present series were in some ways similar to those described in the reports reviewing patients of all age groups.1"' However, in our young patients, symptoms of motor abnormality seemed to occur more often, to occur earlier, and to be more intense, while in previous reports15 the most common symptoms at time of admission were related to in¬ creased intracranial pressure. Fur¬ thermore, at the time of admission signs usually associated with cerebel¬ lar lesions were often prominent, a feature not stressed in adult series.25 The patients in this study with cere¬ bellar syndromes without localizing neurological signs are of interest since they could have been suspected initially of having cerebellar tumors, the more common lesion in this age group. Although tremor is not uncom¬ monly associated with thalamic tu¬ mors, other adventitious movements are rarely seen.1-3 Millichap et al·3 re-
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ported two patients with this associa¬ tion, both of whom were children; one
had chorea and the other dystonic movements. It is interesting that in the present series four patients had involuntary movements. One patient in our series had dysnomia. Cheek and Taveras3 found dysphasia in 11 of their 51 patients. The association of speech disturbance with thalamic le¬ sion has been documented.7 The inci¬ dence of anisocoria in this study does not correspond with the findings of others.'3 This finding has generally been considered of diagnostic signifi¬ cance, the smaller pupil usually ipsi¬ lateral to the tumor. Only two pa¬ tients in our series had seizures prior to treatment. This is in contrast to the reports of others in which the in¬ cidence of seizures was approximate¬ ly 30%.2-3 Among the clinical features, then, that distinguish this group from those that included patients of all ages are an apparent shorter dura¬ tion of symptoms, a moderate in¬ crease in frequency, a greater degree of motor symptomatology in the early illness, and a greater incidence of involuntary movement disorders and especially of signs generally attrib¬ uted to cerebellar disease, while sei¬ zure manifestations were fewer. In cases studied histologically, the tumors were all of glial origin, being either astrocytomas or malignant astrocytomas. This corresponds to other studies that also revealed a high fre¬ quency of astrocytic tumors.14 Other tumors found in those reports were ependymoma, oligodendroglioma, and
ganglioma. We
aware of detailed EEG series of primarily thala¬ mic tumors. Cheek and Taveras3 briefly stated that abnormal EEGs were found in 90% of their cases; in 55% of these the EEG was of local¬ izing value, while in 10% false local¬ izing signs were reported. In our group of children, abnormal EEGs at admission were found in slightly more than 70% of the cases. About one half of these abnormal EEGs could be interpreted only as being consistent with a state of increased intracranial pressure, and correlated are
reports in
not a
well with the clinical picture at the time (Fig 2). The changes in these EEGs, mainly diffuse bursts of highvoltage theta/delta waves occurring in the waking state, have been re¬ ported in subjects with subtentorial tumors8 " and are generally attributed to the occurrence of acute obstructive hydrocephalus and the impinging by a dilated third ventricle on thalamic structures.9 In contrast to these
nonlocalizing signs found as the only abnor¬ mality in about one third (six) of all our subjects, over one third (eight) EEG
exhibited EEGs that could be consid¬ ered more specific for a mass lesion invading the thalamus. These EEGs included ipsilateral depression of nor¬ mal background rhythms, ipsilateral hemispheral polymorphic delta wave activity with no consistent focality, and sigma rhythms (akin to sleep spindles) occurring while patients were awake (Fig 3 and 4), with or without diffuse bursts of slow waves. Jasper and Van Buren10 reported that depression of ipsilateral alpha rhythms may be caused by lesions in¬ volving the mesial and anterior parts of the thalamus. Clinical cases de¬ scribed by Lam,11 Marshall and Walker,12 and Van der Drift and Magnus13 confirmed the depression of alpha activity on the side of le¬ sions destroying the anteromedial part of the thalamus. The latter au¬ thors also described diffuse poly¬ morphic delta rhythms arising ipsilat¬ erally to primary thalamic lesions. Similar findings were described by Hess11 in patients with lesions placed stereotactically in the thalamus. The
sigma rhythms sporadically appear¬ ing in some of these children when awake, and not previously described,
suggest involvement of thalamic structures also. The treatment of this lesion is gen¬
erally considered palliative. Arseni15 reported ten cases in which a thala¬ mic mass was thought grossly to have been totally removed. Not all of these lesions were neoplasms, and the oper¬ ative mortality in that series was 40%. Although the operative mortal¬ ity for craniotomy was only 10% in the present series, only one patient of
the nine who had known partial exci¬ sion is still living. Two other patients underwent what was believed by the operating surgeons to be total re¬ moval of benign tumors with good long-term results. In both cases this was done by another craniotomy when the patient experienced a new progression of symptoms after a pe¬ riod following a partial excision. In this series, as in others, needle biopsy of the tumor had a relatively high risk. Although it is obvious that this is much too small a series with which to study the benefits of x-ray therapy, in many recent cases we have used xray therapy and shunting procedures as necessary without biopsy as the initial mode of therapy. References 1. McKissock W, Paine KWE: Primary tumors of the thalamus. Brain 81:41-63, 1958. 2. Tovi D, Schisano G, Liljeqvist B: Primary tumors of the region of the thalamus. J Neurosurg 18:730-740, 1961. 3. Cheek WR, Taveras JM: Thalamic tumors. J Neurosurg 24:505-513, 1966. 4. Smyth GE, Stern K: Tumors of the thalamus: A clinicopathological study. Brain 61:339\x=req-\ 374, 1938. 5. Ody F: Tumors of the basal ganglia. Arch Neuro Psychiatry 27:249-269, 1932. 6. Millichap JG, Miller RH, Backus RC: Intracranial tumors in childhood. JAMA 179:589-593, 1962. 7. Ojemann GA, Ward AA, Jr: Speech representation in ventrolateral thalamus. Brain 94:669-680, 1971. 8. Daly D, Whelan JL, Bickford RG, et al: The electroencephalogram in cases of tumors of the posterior fossa and third ventricle. Electroencephalogr Clin Neurophysiol 5:203-215, 1953. 9. Martinius J, Matthes A, Lombroso CT: Electroencephalographic features in posterior fossa tumors in children. Electroencephalogr Clin Neurophysiol 25:128-139, 1968. 10. Jasper H, Van Buren JM: Interrelationship between cortex and subcortical structures: Clinical electroencephalographic studies. Electroencephalogr Clin Neurophysiol suppl 4, pp 168-188, 1953. 11. Lam RL: An unusual electroencephalogram associated with thalamic tumor. Electroencephalogr Clin Neurophysiol 2:329-330, 1950. 12. Marshall C, Walker AE: Electroencephalogram in thalamic hemorrhage. Electroencephalogr Clin Neurophysiol 2:99-102, 1950. 13. Van der Drift JHA, Magnus O: Primary thalamic lesions, in Magnus O, Van Lewen S, Cobb WA (eds): Electroencephalography and Cerebral Tumors. Amsterdam, Elsevier Publishing Co, 1961, pp 125-137. 14. Hess R: The influence of stereotactic lesions on the electroencephalogram, in Magnus O, Van Lewen S, Cobb WA (eds): Electroencephalography and Cerebral Tumors. Amsterdam, Elsevier Publishing Co, 1961, pp 166-171. 15. Arseni C: Tumors of the basal ganglia: Their surgical treatment. Arch Neurol Psychiatry 80:18-24, 1958.
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