Agenesis of the Corpus Callosum With Hypothermia Carl
Sadowsky, MD,
Alexander G. Reeves, MD
• A patient with episodic hypothermia and agenesis of the corpus callosum had no direct evidence of hypothalamic-pitultary dysfunction. However, it is specu¬ lated on the basis of a recent clinicopathologic case study that selective hypothalamic involvement is the cause of the hypothermia. Electroencephalograms and treatment with antiseizure medication did not support an epileptic genesis for the episodic hypothermia.
Double, simultaneous, tachistoscopic
stimulation studies revealed an asymme¬ try of response that can be explained by either a functional disconnection of the cerebral hemispheres or bilateral inde¬ pendent and asymmetrical representation of speech mechanisms. (Arch Neurol 32:774-776, 1975)
Agenesis
of the corpus callosum associated with hypothermia has been described previously, to our knowledge, in four patients.13 We re¬ port another patient. REPORT OF A CASE A 33-year-old left-handed man had a 15year history of episodes of sweating, chills,
Accepted for publication Jan 17, 1975. From the Division of Neurology, Department of Medicine, Dartmouth-Hitchcock Medical Cen¬ ter, Hanover, NH. Reprint requests to Division of Neurology, Dartmouth Medical School, Hanover, NH 03755 (Dr Reeves).
and
lethargy.
He denied any aura, loss of or motor seizure activity. After an attack he was often fatigued and would sleep for five to ten hours. Past med¬ ical history, family history, and review of systems were noncontributory. Results of initial physical examination were normal except for a base line temperature of 34.7 C (94 F). Bilateral carotid artericgrams and a pneumoencephalogram (PEG) showed agenesis of the corpus callosum
consciousness,
(Figure). In August 1972 he was admitted to the hospital because of increased frequency of the episodes. Blood pressure was 120/75 mm Hg, pulse rate was 64 beats per min¬ ute, and rectal temperature was 33.7 C (92.6 F). Results of general and neurolog¬ ical examinations were normal, including those of formal visual field testing. Normal laboratory values were obtained for serum electrolytes, calcium, phos¬ phorus, cholesterol, triglycéride, acid phosphatase, and amylase. Vitamin Bi2, fo¬ late, liver, and renal function tests, and complete blood cell count gave normal val¬ ues. Spinal fluid values were normal on four occasions. The ECG revealed sinus bradycardia. Chest and skull x-ray films and brain scan were normal. Several EEGs with nasopharyngeal leads showed symmetrical and diffuse bi¬ lateral slowing of 7 cps with occasional runs of diffuse 4- to 6-cps activity. No sei¬ zure activity occurred following intra¬ venous injection of 30 mg of methohexital sodium. The frequency of hypothermie episodes was unchanged following therapeutic tri-
als of phenytoin, phénobarbital, primidone, chlorpromazine hydrochloride, and predni¬ sone.
Pupillary light, ciliospinal, and accom¬ modation reflexes were normal, and there was no iris response to application of 2.5% methacholine bromide. The blood pressure and pulse rate response to carotid sinus massage, orthostatic challenge, Valsalva maneuver, ice-water immersion of the hand, and sublingually given nitroglycerin were normal. Endocrine evaluation re¬ vealed a normal triiodothyroninerthyroxine ratio, and normal results for five-hour glucose tolerance test, 24-hour urinary 17ketosteroids, and 17-hydroxycorticoids. Blood cortisol levels showed normal diurnal levels and adrenocorticotropic hormone stimulation produced a normal adrenal re¬ sponse. Serum testosterone level was 351 mg/100 ml (normal, 400 to 1,200 mg/100 ml). Serum levels of follicle-stimulating
hormone, luteinizing hormone, growth hormone, and thyroid-stimulating hor¬ mone were all normal. Arginine hydrochlo¬
ride stimulation caused a normal rise in levels of growth hormone. Psychological testing gave a Wechsler Adult Intelligence Scale full-scale IQ of 79
(verbal IQ, 78; performance IQ, 83).
Visual field studies were carried out with the use of single and double simultaneous tachistoscopic stimulation. Visual stimuli were projected at 1/120 of a second on a white screen and, with the subject's gaze fixed on a central dot, single or paired stimuli were presented. In two separate tests (24 samples per test) during which one word was presented to either the right
Downloaded From: http://archneur.jamanetwork.com/ by a Indiana University School of Medicine User on 05/11/2015
field, or a word and figure presented simultaneously to both fields, the patient made no errors in the first test and three errors on the right and or
left visual
were
two
on
fore,
the left in the second test. There¬ significant asymmetry was elic¬
no
ited.
patient was tested with simulta¬ tachistoscopic presentation of two words separated by a dot (ie, Pen Ball); sometime during the testing the sequence The
neous
·
reversed. A total of ten nouns in dif¬ ferent sequences was employed. In 59 tachistoscopic exposures, the subject failed to recognize the word projected into the left field 29 times and made 14 errors on the right Failure to recognize words in both fields simultaneously did not occur. Comparing the two sides as if the probabil¬ ity of error was equal, errors were consid¬ erably greater in the left visual field (P= < .0014). It should be noted that En¬ was
glish-speaking subjects normally recognize
words from the left visual half-field challenged with bilateral tachis¬ toscopic verbal stimuli.'
more
when
Comment
Agenesis of the
corpus callosum is manifestation of dysgenesis of midline telencephalic structures and is frequently associated with abnor¬ malities in the septal region, cingulate gyrus, and other structures.'· Shapiro et al1 suggested that it is not absence of the corpus callosum but the associated diencephalic develop¬ mental defects that lead to the hypo¬ thermia, since surgical sectioning of the corpus callosum is not associated with hypothermia. one
Diencephalic epilepsy, a cause ear¬ by Penfleld,6 was pro¬ posed by Shapiro et al1 to explain the paroxysmal nature of the hypother¬
with lateral
reported
tes
lier advanced
mia in their two
et al7 of episodic hypo¬ thermia but failed to demonstrate the cause of the condition. Hines and Bannie8 described a case of episodic hypothermia that was "cured" by so¬ dium amytal. Unfortunately, EEGs were not available. Noel et al3 found generalized slow waves not depen¬ dent on temperature changes in their patient with corpus callosum agenesis and episodic hypothermia, but did not report a trial of anticonvulsants. Guihard et al2 reported a 7-year-old child with agenesis of the corpus callosum, spontaneous hypothermia, and diabetwo
patients. Duff
cases
Pneumoencephalogram showing typical appearance of agenesis of corpus callosum displacement and elevation of lateral cerebral ventricles (CV) ("bats wings" appearance) and elevation of midline third ventricle (III).
insipidus. Their suggestion that hypothermia and polydipsia had an epileptic origin was unsupported by
any response to anticonvulsant medi¬ cation. In our patient, EEGs demonstrated some runs of diffuse 4- to 6-cps activ¬ ity but delta or spike activity and clinical seizure activity were not noted. There was no change in the frequency of hypothermie episodes during trials with anticonvulsants. The evidence for "diencephalic ep¬ ilepsy" in these patients thus appears to be minimal.
The patient of Noel et al3 was found to have fibrillary gliosis in the arcuate and premammillary areas of the hypothalamus. The authors at¬ tributed the hypothermia to this con¬ dition. Although no direct evidence of
hypothalamic
or
pituitary dysfunc¬
tion was determined in our patient, the similarities of his course and clini¬ cal findings suggest a similar hypo¬ thalamic basis for the hypothermia. Extensive behavioral studies in an¬ imals and humans with surgical divi¬ sion of the corpus callosum have es¬ tablished the importance of this
Downloaded From: http://archneur.jamanetwork.com/ by a Indiana University School of Medicine User on 05/11/2015
structure as a communicating link be¬ tween the hemispheres.9
In contrast, patients with congeni¬ tal absence of the corpus callosum have not revealed clear deficits in interhemispheric transfer of informa¬ tion although they have consistently revealed defects in perceptuomotor coordination.1012 It has been postu¬ lated that in these patients lateralized cerebral functions, such as speech and visuospatial capabilities, develop bilaterally or that an increase in the size of the anterior and other commissural pathways compensates for callosal lack.913 Tachistoscopic study revealed that our patient made more errors in read¬ ing words in the left visual field than in the right. The patient performed poorly only on simultaneous presenta¬ tion of words to both fields but could accurately name words presented to either field alone.
There are several possible inter¬ pretations of the data. The patient's performance was similar to the ex¬ tinction accompanying right poste¬ rior parietal lesions in which a single stimulus presented to the left visual field is perceived but bilateral, simul¬ taneously presented stimuli are not perceived in the left field. Neurolog¬ ical examination, PEG, arteriogram, and EEG, however, gave no evidence that the patient had a congenital or acquired abnormality of the right parietal region. Another
possibility
is that lan¬
potential developed indepen¬ dently in each hemisphere, and that each hemisphere had access to the speech pathways. When both hemi¬ spheres were presented with the stimulus, possibly the left hemisphere had dominant access to the speech guage
mechanisms. This could be because the outflow pathway was in the left
hemisphere and was reached by the right hemisphere through the ante¬ rior
commissure, had
hemisphere which competed
or a
because each
speech pathway,
in the brain stem. A third alternative is that of a functional cerebral disconnection in difficult tasks of simultaneous visual recognition (tachistoscopic word pre¬ sentation) in a patient with absence of the corpus callosum. In this case the stimulus projected to the right hemisphere would not be well recog¬ nized because of a defect of trans¬ mission of the material to a lan¬ guage-dominant left hemisphere. Our data do not allow us to specu¬ late as to which of the last two hypotheses is most likely to be correct. We await further study of other patients with agenesis of the corpus callosum. This study was supported in part Health Service grant M H 25621.
by
Public
References Shapiro W, Williams G, Plum F: Spontane¬ hypothermia accompanying age¬ nesis of the corpus callosum. Brain 92:423-436, 1.
ous
recurrent
1969. 2. Guihard
J, Velot-Leroy A, Poitrat C: Hy¬ pothermia spontanée réeedivante avec agenesie du corps calleux. Sem Hop Paris (Ann Pediat) 47:645-656, 1971. 3. Noel , Hubert JP, Ectors EM, et al: Age¬
nesis of the corpus callosum associated with re¬ lapsing hypothermia. Brain 96:359-368, 1973. 4. Hiñes D: Bilateral tachystoscopic recogni¬ tion of verbal and nonverbal stimuli. Cortex 8:315-322, 1972. 5. Loeser J, Alvord E: Clinicopathological cor-
relations in agenesis of the corpus callosum. Neurology 18:745-756, 1968. 6. Penfield W: Diencephalic autonomie ep¬ ilepsy. Arch Neurol Psychiatry 22:358-374,1929. 7. Duff R, Farraut PC, Leveaux VM, et al: Spontaneous periodic hypothermia. Q J Med
30:329-338, 1961. 8. Hines E, Bannie E: Intermittent hypo¬ thermia with disabling hyperhidrosis. Mayo Clin Proc 9:705-708, 1934. 9. Sperry R, Gazzaniga M, Bogen J: Inter-
hemispheric relationships: The neocortical com¬ missures; syndromes of hemispheric dis¬ connection, in Vinkin PJ, Bruyn GW (eds): Handbook of Clinical Neurology. Amsterdam,
North-Holland Co, 1969, vol 4, pp 273-290. 10. Ettlinger G, Blakemore CB, Milner AD, et al: Agenesis of the corpus callosum: A behavioral
investigation.
Brain 95:327-346, 1972. 11. Jeeves MA: Psychological studies of three cases of congenital agenesis of the corpus callo¬ sum. Ciba Found Study Group 20:73-94, 1965. 12. Sheremata WA, Deonna TW, Romanul FCA: Agenesis of the corpus callosum and interhemispheric transfer of information. Neurology 23:390, 1973. 13. Gazzaniga M: The Bisected Brain. New York, Appleton-Century-Crofts Ine, 1970.
Downloaded From: http://archneur.jamanetwork.com/ by a Indiana University School of Medicine User on 05/11/2015
Sadowsky, MD,
Alexander G. Reeves, MD
• A patient with episodic hypothermia and agenesis of the corpus callosum had no direct evidence of hypothalamic-pitultary dysfunction. However, it is specu¬ lated on the basis of a recent clinicopathologic case study that selective hypothalamic involvement is the cause of the hypothermia. Electroencephalograms and treatment with antiseizure medication did not support an epileptic genesis for the episodic hypothermia.
Double, simultaneous, tachistoscopic
stimulation studies revealed an asymme¬ try of response that can be explained by either a functional disconnection of the cerebral hemispheres or bilateral inde¬ pendent and asymmetrical representation of speech mechanisms. (Arch Neurol 32:774-776, 1975)
Agenesis
of the corpus callosum associated with hypothermia has been described previously, to our knowledge, in four patients.13 We re¬ port another patient. REPORT OF A CASE A 33-year-old left-handed man had a 15year history of episodes of sweating, chills,
Accepted for publication Jan 17, 1975. From the Division of Neurology, Department of Medicine, Dartmouth-Hitchcock Medical Cen¬ ter, Hanover, NH. Reprint requests to Division of Neurology, Dartmouth Medical School, Hanover, NH 03755 (Dr Reeves).
and
lethargy.
He denied any aura, loss of or motor seizure activity. After an attack he was often fatigued and would sleep for five to ten hours. Past med¬ ical history, family history, and review of systems were noncontributory. Results of initial physical examination were normal except for a base line temperature of 34.7 C (94 F). Bilateral carotid artericgrams and a pneumoencephalogram (PEG) showed agenesis of the corpus callosum
consciousness,
(Figure). In August 1972 he was admitted to the hospital because of increased frequency of the episodes. Blood pressure was 120/75 mm Hg, pulse rate was 64 beats per min¬ ute, and rectal temperature was 33.7 C (92.6 F). Results of general and neurolog¬ ical examinations were normal, including those of formal visual field testing. Normal laboratory values were obtained for serum electrolytes, calcium, phos¬ phorus, cholesterol, triglycéride, acid phosphatase, and amylase. Vitamin Bi2, fo¬ late, liver, and renal function tests, and complete blood cell count gave normal val¬ ues. Spinal fluid values were normal on four occasions. The ECG revealed sinus bradycardia. Chest and skull x-ray films and brain scan were normal. Several EEGs with nasopharyngeal leads showed symmetrical and diffuse bi¬ lateral slowing of 7 cps with occasional runs of diffuse 4- to 6-cps activity. No sei¬ zure activity occurred following intra¬ venous injection of 30 mg of methohexital sodium. The frequency of hypothermie episodes was unchanged following therapeutic tri-
als of phenytoin, phénobarbital, primidone, chlorpromazine hydrochloride, and predni¬ sone.
Pupillary light, ciliospinal, and accom¬ modation reflexes were normal, and there was no iris response to application of 2.5% methacholine bromide. The blood pressure and pulse rate response to carotid sinus massage, orthostatic challenge, Valsalva maneuver, ice-water immersion of the hand, and sublingually given nitroglycerin were normal. Endocrine evaluation re¬ vealed a normal triiodothyroninerthyroxine ratio, and normal results for five-hour glucose tolerance test, 24-hour urinary 17ketosteroids, and 17-hydroxycorticoids. Blood cortisol levels showed normal diurnal levels and adrenocorticotropic hormone stimulation produced a normal adrenal re¬ sponse. Serum testosterone level was 351 mg/100 ml (normal, 400 to 1,200 mg/100 ml). Serum levels of follicle-stimulating
hormone, luteinizing hormone, growth hormone, and thyroid-stimulating hor¬ mone were all normal. Arginine hydrochlo¬
ride stimulation caused a normal rise in levels of growth hormone. Psychological testing gave a Wechsler Adult Intelligence Scale full-scale IQ of 79
(verbal IQ, 78; performance IQ, 83).
Visual field studies were carried out with the use of single and double simultaneous tachistoscopic stimulation. Visual stimuli were projected at 1/120 of a second on a white screen and, with the subject's gaze fixed on a central dot, single or paired stimuli were presented. In two separate tests (24 samples per test) during which one word was presented to either the right
Downloaded From: http://archneur.jamanetwork.com/ by a Indiana University School of Medicine User on 05/11/2015
field, or a word and figure presented simultaneously to both fields, the patient made no errors in the first test and three errors on the right and or
left visual
were
two
on
fore,
the left in the second test. There¬ significant asymmetry was elic¬
no
ited.
patient was tested with simulta¬ tachistoscopic presentation of two words separated by a dot (ie, Pen Ball); sometime during the testing the sequence The
neous
·
reversed. A total of ten nouns in dif¬ ferent sequences was employed. In 59 tachistoscopic exposures, the subject failed to recognize the word projected into the left field 29 times and made 14 errors on the right Failure to recognize words in both fields simultaneously did not occur. Comparing the two sides as if the probabil¬ ity of error was equal, errors were consid¬ erably greater in the left visual field (P= < .0014). It should be noted that En¬ was
glish-speaking subjects normally recognize
words from the left visual half-field challenged with bilateral tachis¬ toscopic verbal stimuli.'
more
when
Comment
Agenesis of the
corpus callosum is manifestation of dysgenesis of midline telencephalic structures and is frequently associated with abnor¬ malities in the septal region, cingulate gyrus, and other structures.'· Shapiro et al1 suggested that it is not absence of the corpus callosum but the associated diencephalic develop¬ mental defects that lead to the hypo¬ thermia, since surgical sectioning of the corpus callosum is not associated with hypothermia. one
Diencephalic epilepsy, a cause ear¬ by Penfleld,6 was pro¬ posed by Shapiro et al1 to explain the paroxysmal nature of the hypother¬
with lateral
reported
tes
lier advanced
mia in their two
et al7 of episodic hypo¬ thermia but failed to demonstrate the cause of the condition. Hines and Bannie8 described a case of episodic hypothermia that was "cured" by so¬ dium amytal. Unfortunately, EEGs were not available. Noel et al3 found generalized slow waves not depen¬ dent on temperature changes in their patient with corpus callosum agenesis and episodic hypothermia, but did not report a trial of anticonvulsants. Guihard et al2 reported a 7-year-old child with agenesis of the corpus callosum, spontaneous hypothermia, and diabetwo
patients. Duff
cases
Pneumoencephalogram showing typical appearance of agenesis of corpus callosum displacement and elevation of lateral cerebral ventricles (CV) ("bats wings" appearance) and elevation of midline third ventricle (III).
insipidus. Their suggestion that hypothermia and polydipsia had an epileptic origin was unsupported by
any response to anticonvulsant medi¬ cation. In our patient, EEGs demonstrated some runs of diffuse 4- to 6-cps activ¬ ity but delta or spike activity and clinical seizure activity were not noted. There was no change in the frequency of hypothermie episodes during trials with anticonvulsants. The evidence for "diencephalic ep¬ ilepsy" in these patients thus appears to be minimal.
The patient of Noel et al3 was found to have fibrillary gliosis in the arcuate and premammillary areas of the hypothalamus. The authors at¬ tributed the hypothermia to this con¬ dition. Although no direct evidence of
hypothalamic
or
pituitary dysfunc¬
tion was determined in our patient, the similarities of his course and clini¬ cal findings suggest a similar hypo¬ thalamic basis for the hypothermia. Extensive behavioral studies in an¬ imals and humans with surgical divi¬ sion of the corpus callosum have es¬ tablished the importance of this
Downloaded From: http://archneur.jamanetwork.com/ by a Indiana University School of Medicine User on 05/11/2015
structure as a communicating link be¬ tween the hemispheres.9
In contrast, patients with congeni¬ tal absence of the corpus callosum have not revealed clear deficits in interhemispheric transfer of informa¬ tion although they have consistently revealed defects in perceptuomotor coordination.1012 It has been postu¬ lated that in these patients lateralized cerebral functions, such as speech and visuospatial capabilities, develop bilaterally or that an increase in the size of the anterior and other commissural pathways compensates for callosal lack.913 Tachistoscopic study revealed that our patient made more errors in read¬ ing words in the left visual field than in the right. The patient performed poorly only on simultaneous presenta¬ tion of words to both fields but could accurately name words presented to either field alone.
There are several possible inter¬ pretations of the data. The patient's performance was similar to the ex¬ tinction accompanying right poste¬ rior parietal lesions in which a single stimulus presented to the left visual field is perceived but bilateral, simul¬ taneously presented stimuli are not perceived in the left field. Neurolog¬ ical examination, PEG, arteriogram, and EEG, however, gave no evidence that the patient had a congenital or acquired abnormality of the right parietal region. Another
possibility
is that lan¬
potential developed indepen¬ dently in each hemisphere, and that each hemisphere had access to the speech pathways. When both hemi¬ spheres were presented with the stimulus, possibly the left hemisphere had dominant access to the speech guage
mechanisms. This could be because the outflow pathway was in the left
hemisphere and was reached by the right hemisphere through the ante¬ rior
commissure, had
hemisphere which competed
or a
because each
speech pathway,
in the brain stem. A third alternative is that of a functional cerebral disconnection in difficult tasks of simultaneous visual recognition (tachistoscopic word pre¬ sentation) in a patient with absence of the corpus callosum. In this case the stimulus projected to the right hemisphere would not be well recog¬ nized because of a defect of trans¬ mission of the material to a lan¬ guage-dominant left hemisphere. Our data do not allow us to specu¬ late as to which of the last two hypotheses is most likely to be correct. We await further study of other patients with agenesis of the corpus callosum. This study was supported in part Health Service grant M H 25621.
by
Public
References Shapiro W, Williams G, Plum F: Spontane¬ hypothermia accompanying age¬ nesis of the corpus callosum. Brain 92:423-436, 1.
ous
recurrent
1969. 2. Guihard
J, Velot-Leroy A, Poitrat C: Hy¬ pothermia spontanée réeedivante avec agenesie du corps calleux. Sem Hop Paris (Ann Pediat) 47:645-656, 1971. 3. Noel , Hubert JP, Ectors EM, et al: Age¬
nesis of the corpus callosum associated with re¬ lapsing hypothermia. Brain 96:359-368, 1973. 4. Hiñes D: Bilateral tachystoscopic recogni¬ tion of verbal and nonverbal stimuli. Cortex 8:315-322, 1972. 5. Loeser J, Alvord E: Clinicopathological cor-
relations in agenesis of the corpus callosum. Neurology 18:745-756, 1968. 6. Penfield W: Diencephalic autonomie ep¬ ilepsy. Arch Neurol Psychiatry 22:358-374,1929. 7. Duff R, Farraut PC, Leveaux VM, et al: Spontaneous periodic hypothermia. Q J Med
30:329-338, 1961. 8. Hines E, Bannie E: Intermittent hypo¬ thermia with disabling hyperhidrosis. Mayo Clin Proc 9:705-708, 1934. 9. Sperry R, Gazzaniga M, Bogen J: Inter-
hemispheric relationships: The neocortical com¬ missures; syndromes of hemispheric dis¬ connection, in Vinkin PJ, Bruyn GW (eds): Handbook of Clinical Neurology. Amsterdam,
North-Holland Co, 1969, vol 4, pp 273-290. 10. Ettlinger G, Blakemore CB, Milner AD, et al: Agenesis of the corpus callosum: A behavioral
investigation.
Brain 95:327-346, 1972. 11. Jeeves MA: Psychological studies of three cases of congenital agenesis of the corpus callo¬ sum. Ciba Found Study Group 20:73-94, 1965. 12. Sheremata WA, Deonna TW, Romanul FCA: Agenesis of the corpus callosum and interhemispheric transfer of information. Neurology 23:390, 1973. 13. Gazzaniga M: The Bisected Brain. New York, Appleton-Century-Crofts Ine, 1970.
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