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Hypothermia, Wernicke encephalopathy and multiple sclerosis Geny C, Pradat PF, Yulis J, Walter S , Cesaro, Degos JD. Hypothermia, Wernicke encephalopathy and multiple sclerosis. Acta Neurol Scand 1992: 86: 632-634. 0 Munksgaard 1992. Neurological exacerbation observed in MS patients is usually related to a demyelinating process. We report two patients where hypothermia (32.4" C and 32.5"C) and neurological exacerbation were probably due to a Wernicke encephalopathy (WE). The clinical features and the rapid efficiency of parenteral thiamine were suggestive of WE. Hypothermia is an exceptional symptom observed in MS and has been considered as resulting from hypothalamic demyelination; these two cases showed that WE which is another cause of reversible hypothermia, can be associated with MS
The first relapses of MS are easy to identify. In older and disabled patients, disorders due to another neurologic disease could be wrongly attributed to the demyelinating process. Hypothalamic dysfunction are exceptionally reported in MS: acute or chronic hypothermia (1-3), or syndrome of inappropriate antidiuretic hormone secretion (4). We report two MS patients in whom hypothermia and neurological exacerbation were probably due to a Wernicke encephalopathy (WE). Case reports
Patient 1 (n " 89 280876). A 63-year-old woman with a 25-year history of clinically definite MS was admitted in December 1989 for a one-week history of worsening gait disorders with several falls. She did not consume alcohol. Psychomotor slowing, mild paraparesis, bilateral Babinski sign, paresthesia in the right arm, right arm ataxia and mild postural tremor were noted. During hospitalization, her temperature varied from 35.4"C to 36.6"C (mean = 36.25 "C). Cerebral MRI showed diffuse signal abnormalities in white matter, but not in the hypothalamic region. She left the service with an unmodified neurological status, despite ACTH therapy. She was readmitted two months later. The patient complained of visual perception of red and black spots. She was depressive and paranoiac and was unable to stand up without help. Neurological symptoms worsened with outbreak of moderate con-
632
C. Geny, P. F. Pradat, J. Yulis, S. Waiter, D. Cesaro, J. D. Degos Department of Neurosciences, Henri Mondor Hospital, Creteil, France
C. Geny, Department of Neurosciences, HBpital Henri Mondor, F-94010 Creteil, France Accepted for publication April 27, 1 9 9 2
fusion, psychomotor slowing and dysarthria. There was no oculomotor palsy. The rectal temperature was 32.4"C. Blood and urine cultures were negative. Blood cell count, serum electrolytes and thyroid function were in the normal range. Glycemia was at 3.6 mmol/l. ASAT and ALAT were mildly and provisionally increased, seric albumin was diminished at 31.7 g/1 (N> 37). The first day, despite passive rewarming, the rectal temperature remained low (Fig. 1). The second day, treatment with parenteral thiamine (600 mg per day) produced a normalisation of the temperature. Confusion and psychiatric disturbances improved first and the gait disorder second, in two weeks. During three weeks hospitalization, her temperature remained in the normal range.
;:1 'C
I
38
31 30
-
I I PATIENT2
1
t . . . . . . . . . . . . . Day1
Day2
Day3
Day4
Day5
--J-i
Day6
Day7
---
Fig. 1. Evolution of the temperature ( " C )after thiamine therapy (W-W) Thiamine therapy in Patient 1 (0-0) Thiamine therapy in patient 2.
Hypothermia, encephalopathy & MS
Patient 2 (No90 064193) . A 68-year-old woman was hospitalized in September 1990 with a 3-week history of dysarthria and gait disorder. She had a 32-year history of clinically definite MS and was not a alcoholic. The patient was able to walk with a lot of difficulty and lived alone. For one month, she had refused or rejected meat. Despite 3 weeks of steroid therapy introduced by her physician, her condition worsened and she was admitted to the emergency unit. She was disoriented and drowsy and had a severe paraparesis with bilateral Babinski sign, dysarthria, partial right lateral rectus palsy, bilateral asterixis and kinetic cerebellar syndrome in the upper arms. Her rectal temperature was 31.6"C. Bradycardia at 50 was noted. Serum electrolytes and glycemia were normal. CSF contained 1 lymphocyte/ ml, 0.39 mg/dl of protein with normal electrophoretic pattern. There was hypoalbuminemia (18.9 g/1 N > 37). Plasmatic folic acid was decreased (7.5 nmoles/l N > 11.3). Vitamins B 12 and E were in the normal range. T3 was slightly decreased 0.45 pg/l (N > 0.8), but T4 and TSH were in normal range. Urine culture revealed an infection by Escherichia coli and Proteus vulgaris. Blood cultures were negative. Treatment with intravenous thiamine (600 mg daily) was started 12 h after admission and resulted in normalisation of the temperature (Fig. 1). The third day, thiamine was stopped and the temperature rapidly dropped again. Thiamine was reintroduced and her temperature returned to normal values. The first neurologic signs to disappear were the oculo-
motor paresis, stupor and asterixis. The dysarthria improved more slowly. Complete clinical recovery was attained within one month. Cerebral MRI performed three weeks later, showed multiple high signal lesions in periventricular areas, but no abnormalities in the hypothalamic region. Discussion
The neurologic exacerbation observed in these two MS patients is probably related to WE rather than to MS relapse. The second patient had the typical triad of WE: mental confusion, gait disorder and ocular disturbances (5). Certainly, these signs could be seen in MS as in WE, but the rapid improvement of neurologic symptoms obtained with thiamine infusion and the relapse of hypothermia after interruption of vitamin therapy support the diagnosis of WE. In the first patient, clinical features are less suggestive of WE. However, the good response of hypothermia and neurologic symptoms to thiamine during parenteral administration, but not to ACTH is striking. Hypothermia is a rare, but well known, sign of WE and is probably secondary to lesions in posterior hypothalamus. The regression of hypothermia after thiamine infusion in a few hours has been pointed out (6). In the Fischbeck study, WE was the third cause of hypothermia (18%) (7). Other brain lesions responsible for hypothermia were rare: brain tumor, sarcoidosis, stroke, ventricular shunt embolism, fat emboli, trauma, haematoma (7-10). A neu-
Table 1. Review of the reported cases of hypothermia in MS patients References Age (yr), sex Disability Status Scale Duration of MS (YR) Number of hypothermic episodes Minimal rectal temperature ('C)
Sullivan'
Sullivan'
41, F 7 1
52, F 8 24
chronic (9 months) 32.6
Stupor Coma Spasticity Mutism Paraparesis Myoclonus Bladder dysfunction Dysarthria Dysphagia Nystagmus Memory deficit Cerebellar syndrome
t
Anemia Thrombopenia Hyponatremia
t t
t t t
chronic
55, F 6 24
31
chronic? (33 months) 32
t t
t t
( 12 months)
Lammens'
Lammed
Ghawche3
51, F
52, M
38, F
7
7
22
16
1
?
32
t
Present study
14
63, F 4 25
68, F 6 32
3
1
1
32
32.8
32.4
31.6
t
t
t
t
-It t
t t
t t t
t
t
t
t
t
t
+
+
t t
-
t t t
+
t
t t -
633
Geny et a].
ropathologic post-mortem study disclosed that the frequency of WE is underestimated during the patient’s life time (11). Diagnosis is easy when the patient is alcoholic and has the typical triad, but WE symptomatology may consist of one of these manifestations alone (5) and can occur in other conditions: starvation, AIDS, dialysis, persistent vomiting, malignancies, systemic diseases, parented nutrition (5, 12, 13). Hypothermia has been reported in six other MS patients (Table 1) (1-3). These patients were old and suffered from severe MS. The decrease of the rectal temperature could be chronic (9 and 12 months), single or relapsing (4 events). Associated symptoms were various, but stupor was constant. Other signs of hypothalamic dysfunction (hypoglycemia or syndrome of inappropriate antidiuretic hormone secretion) were reported in only two cases. Necropsy has been performed in one of them and revealed only axon swelling and cell loss in hypothalamic region (2). In fact, it seems that demyelinated,plaques which are frequently observed in hypothalamic regions, are rarely associated with hypothalamic dysfunction (14- 16). The dramatic improvement observed after thiamine therapy in our MS patients with neurologic exacerbation and hypothermia led us to suggest they suffered from WE. If hypothermia could be secondary to hypothalamic demyelination in MS patients, the possibility of associated WE must not been ignored and thiamine therapy should be rapidly started. Acknowledgement This work was supported by the French Association pour la recherche sur la SclCrose en Plaques.
References 1. SULLIVAN F, HUTCHINSON M, BAHANDEKA S, MOORE
RE. Chronic hypothermia in multiple sclerosis. J Neurol Neurosurg Psychiatry 1987: 50: 813-815.
634
2. LAMMENS M, LISSOIR F, CARTONH. Hypothermia in three patients with multiple sclerosis. Clin Neurol Neurosurg 1989: 91: 117-121. 3. GHAWCHE F, DESTEE A. Hypothermie et sclCrose en plaques. 4. 5.
6. 7.
Un cas avec trois Cpisodes d’hypothermie transitoire. Rev Neurol 1990: 146: 767-769. APPLED, KEINES K, BIEHLJP. The syndrome of inappropriate antidiuretic hormone secretion in multiple sclerosis. Arch Int Med 1978: 138: 1713-1714. VICTORM. The Wernicke-Korsakoff syndrome. In: VINKEN PJ, BRUYNGW, eds. Handbook of clinical neurology. Amsterdam: Elsevier, 1965: 28: 243-268. MANNMW, DEGOS JD. L‘hypothermie dans l’enckphalopathie de Wernicke. Rev Neurol 1987: 143: 684-686. FISCHBECK KH, SIMONRP. Neurological manifestations of accidental hypothermia. Ann Neurol 1981: 10: 384-387.
PJ, BELL JI, COLLINSKJ, FRACKOWIAK 8. RATCLIFFE RS, RUDGE P. Late onset post-traumatic hypothalamic hypothermia. J Neurol Neurosurg Psychiatry 1983: 46: 7274. G, CAMBONH, DORMONT D, RICHARDA, 9. GAYMARD
DEROUESNE C. Hypothermia in a mesodiencephalic haematoma. J Neurol Neurosurg Psychiatry 1990: 53: 10141015. 10. BRANCHEF, BURGERPC, BREUVER DL. Hypothermia in
a case of hypothalamic infection and sarcoidosis. Arch Neurol 1971: 25: 245-255. 11. HARPERC. Wernicke’s encephalopathy: a more common disease than realised. A neuropathological study of 51 cases. J Neurol Neurosurg Psychiatry 1978: 42: 226-231. WC, SMYTHHS. 12. JAGADHA V, DECKJHN, HALLIDAY Wernicke’s encephalopathy in patients on peritoneal dialysis or hemodialysis. Ann Neurol 1987: 21: 78-84.
THIERAUFP, IGLESIAS J, 13. SCHWENKJ, GOSZTONYI, LANGERE. Wernicke’s encephalopathy in two patients with acquired immunodeficiency syndrome. J Neurol 1990: 237: 445 -447. 14. KAMALIAN. Lateral hypothalamic demyelination and cachexia in a case of malignant multiple sclerosis. Neurology 1975: 25: 25-30. 15. BIGNAMIA, GHERARDI D, DALLO G. Sclerosi a placche
acuta alocalizzazone ipotalamica con sintomatologica psichica di tip malinconico. Rivista di Neurologia 1961: 31: 240-268. 16. LUMSDEN CE. The neuropathology of multiple sclerosis. In:
VINKENPJ, BRUYNGW, eds. Handbook of clinical neurology. Amsterdam: Elsevier, 1965: 9: 217-309.
Hypothermia, Wernicke encephalopathy and multiple sclerosis Geny C, Pradat PF, Yulis J, Walter S , Cesaro, Degos JD. Hypothermia, Wernicke encephalopathy and multiple sclerosis. Acta Neurol Scand 1992: 86: 632-634. 0 Munksgaard 1992. Neurological exacerbation observed in MS patients is usually related to a demyelinating process. We report two patients where hypothermia (32.4" C and 32.5"C) and neurological exacerbation were probably due to a Wernicke encephalopathy (WE). The clinical features and the rapid efficiency of parenteral thiamine were suggestive of WE. Hypothermia is an exceptional symptom observed in MS and has been considered as resulting from hypothalamic demyelination; these two cases showed that WE which is another cause of reversible hypothermia, can be associated with MS
The first relapses of MS are easy to identify. In older and disabled patients, disorders due to another neurologic disease could be wrongly attributed to the demyelinating process. Hypothalamic dysfunction are exceptionally reported in MS: acute or chronic hypothermia (1-3), or syndrome of inappropriate antidiuretic hormone secretion (4). We report two MS patients in whom hypothermia and neurological exacerbation were probably due to a Wernicke encephalopathy (WE). Case reports
Patient 1 (n " 89 280876). A 63-year-old woman with a 25-year history of clinically definite MS was admitted in December 1989 for a one-week history of worsening gait disorders with several falls. She did not consume alcohol. Psychomotor slowing, mild paraparesis, bilateral Babinski sign, paresthesia in the right arm, right arm ataxia and mild postural tremor were noted. During hospitalization, her temperature varied from 35.4"C to 36.6"C (mean = 36.25 "C). Cerebral MRI showed diffuse signal abnormalities in white matter, but not in the hypothalamic region. She left the service with an unmodified neurological status, despite ACTH therapy. She was readmitted two months later. The patient complained of visual perception of red and black spots. She was depressive and paranoiac and was unable to stand up without help. Neurological symptoms worsened with outbreak of moderate con-
632
C. Geny, P. F. Pradat, J. Yulis, S. Waiter, D. Cesaro, J. D. Degos Department of Neurosciences, Henri Mondor Hospital, Creteil, France
C. Geny, Department of Neurosciences, HBpital Henri Mondor, F-94010 Creteil, France Accepted for publication April 27, 1 9 9 2
fusion, psychomotor slowing and dysarthria. There was no oculomotor palsy. The rectal temperature was 32.4"C. Blood and urine cultures were negative. Blood cell count, serum electrolytes and thyroid function were in the normal range. Glycemia was at 3.6 mmol/l. ASAT and ALAT were mildly and provisionally increased, seric albumin was diminished at 31.7 g/1 (N> 37). The first day, despite passive rewarming, the rectal temperature remained low (Fig. 1). The second day, treatment with parenteral thiamine (600 mg per day) produced a normalisation of the temperature. Confusion and psychiatric disturbances improved first and the gait disorder second, in two weeks. During three weeks hospitalization, her temperature remained in the normal range.
;:1 'C
I
38
31 30
-
I I PATIENT2
1
t . . . . . . . . . . . . . Day1
Day2
Day3
Day4
Day5
--J-i
Day6
Day7
---
Fig. 1. Evolution of the temperature ( " C )after thiamine therapy (W-W) Thiamine therapy in Patient 1 (0-0) Thiamine therapy in patient 2.
Hypothermia, encephalopathy & MS
Patient 2 (No90 064193) . A 68-year-old woman was hospitalized in September 1990 with a 3-week history of dysarthria and gait disorder. She had a 32-year history of clinically definite MS and was not a alcoholic. The patient was able to walk with a lot of difficulty and lived alone. For one month, she had refused or rejected meat. Despite 3 weeks of steroid therapy introduced by her physician, her condition worsened and she was admitted to the emergency unit. She was disoriented and drowsy and had a severe paraparesis with bilateral Babinski sign, dysarthria, partial right lateral rectus palsy, bilateral asterixis and kinetic cerebellar syndrome in the upper arms. Her rectal temperature was 31.6"C. Bradycardia at 50 was noted. Serum electrolytes and glycemia were normal. CSF contained 1 lymphocyte/ ml, 0.39 mg/dl of protein with normal electrophoretic pattern. There was hypoalbuminemia (18.9 g/1 N > 37). Plasmatic folic acid was decreased (7.5 nmoles/l N > 11.3). Vitamins B 12 and E were in the normal range. T3 was slightly decreased 0.45 pg/l (N > 0.8), but T4 and TSH were in normal range. Urine culture revealed an infection by Escherichia coli and Proteus vulgaris. Blood cultures were negative. Treatment with intravenous thiamine (600 mg daily) was started 12 h after admission and resulted in normalisation of the temperature (Fig. 1). The third day, thiamine was stopped and the temperature rapidly dropped again. Thiamine was reintroduced and her temperature returned to normal values. The first neurologic signs to disappear were the oculo-
motor paresis, stupor and asterixis. The dysarthria improved more slowly. Complete clinical recovery was attained within one month. Cerebral MRI performed three weeks later, showed multiple high signal lesions in periventricular areas, but no abnormalities in the hypothalamic region. Discussion
The neurologic exacerbation observed in these two MS patients is probably related to WE rather than to MS relapse. The second patient had the typical triad of WE: mental confusion, gait disorder and ocular disturbances (5). Certainly, these signs could be seen in MS as in WE, but the rapid improvement of neurologic symptoms obtained with thiamine infusion and the relapse of hypothermia after interruption of vitamin therapy support the diagnosis of WE. In the first patient, clinical features are less suggestive of WE. However, the good response of hypothermia and neurologic symptoms to thiamine during parenteral administration, but not to ACTH is striking. Hypothermia is a rare, but well known, sign of WE and is probably secondary to lesions in posterior hypothalamus. The regression of hypothermia after thiamine infusion in a few hours has been pointed out (6). In the Fischbeck study, WE was the third cause of hypothermia (18%) (7). Other brain lesions responsible for hypothermia were rare: brain tumor, sarcoidosis, stroke, ventricular shunt embolism, fat emboli, trauma, haematoma (7-10). A neu-
Table 1. Review of the reported cases of hypothermia in MS patients References Age (yr), sex Disability Status Scale Duration of MS (YR) Number of hypothermic episodes Minimal rectal temperature ('C)
Sullivan'
Sullivan'
41, F 7 1
52, F 8 24
chronic (9 months) 32.6
Stupor Coma Spasticity Mutism Paraparesis Myoclonus Bladder dysfunction Dysarthria Dysphagia Nystagmus Memory deficit Cerebellar syndrome
t
Anemia Thrombopenia Hyponatremia
t t
t t t
chronic
55, F 6 24
31
chronic? (33 months) 32
t t
t t
( 12 months)
Lammens'
Lammed
Ghawche3
51, F
52, M
38, F
7
7
22
16
1
?
32
t
Present study
14
63, F 4 25
68, F 6 32
3
1
1
32
32.8
32.4
31.6
t
t
t
t
-It t
t t
t t t
t
t
t
t
t
t
+
+
t t
-
t t t
+
t
t t -
633
Geny et a].
ropathologic post-mortem study disclosed that the frequency of WE is underestimated during the patient’s life time (11). Diagnosis is easy when the patient is alcoholic and has the typical triad, but WE symptomatology may consist of one of these manifestations alone (5) and can occur in other conditions: starvation, AIDS, dialysis, persistent vomiting, malignancies, systemic diseases, parented nutrition (5, 12, 13). Hypothermia has been reported in six other MS patients (Table 1) (1-3). These patients were old and suffered from severe MS. The decrease of the rectal temperature could be chronic (9 and 12 months), single or relapsing (4 events). Associated symptoms were various, but stupor was constant. Other signs of hypothalamic dysfunction (hypoglycemia or syndrome of inappropriate antidiuretic hormone secretion) were reported in only two cases. Necropsy has been performed in one of them and revealed only axon swelling and cell loss in hypothalamic region (2). In fact, it seems that demyelinated,plaques which are frequently observed in hypothalamic regions, are rarely associated with hypothalamic dysfunction (14- 16). The dramatic improvement observed after thiamine therapy in our MS patients with neurologic exacerbation and hypothermia led us to suggest they suffered from WE. If hypothermia could be secondary to hypothalamic demyelination in MS patients, the possibility of associated WE must not been ignored and thiamine therapy should be rapidly started. Acknowledgement This work was supported by the French Association pour la recherche sur la SclCrose en Plaques.
References 1. SULLIVAN F, HUTCHINSON M, BAHANDEKA S, MOORE
RE. Chronic hypothermia in multiple sclerosis. J Neurol Neurosurg Psychiatry 1987: 50: 813-815.
634
2. LAMMENS M, LISSOIR F, CARTONH. Hypothermia in three patients with multiple sclerosis. Clin Neurol Neurosurg 1989: 91: 117-121. 3. GHAWCHE F, DESTEE A. Hypothermie et sclCrose en plaques. 4. 5.
6. 7.
Un cas avec trois Cpisodes d’hypothermie transitoire. Rev Neurol 1990: 146: 767-769. APPLED, KEINES K, BIEHLJP. The syndrome of inappropriate antidiuretic hormone secretion in multiple sclerosis. Arch Int Med 1978: 138: 1713-1714. VICTORM. The Wernicke-Korsakoff syndrome. In: VINKEN PJ, BRUYNGW, eds. Handbook of clinical neurology. Amsterdam: Elsevier, 1965: 28: 243-268. MANNMW, DEGOS JD. L‘hypothermie dans l’enckphalopathie de Wernicke. Rev Neurol 1987: 143: 684-686. FISCHBECK KH, SIMONRP. Neurological manifestations of accidental hypothermia. Ann Neurol 1981: 10: 384-387.
PJ, BELL JI, COLLINSKJ, FRACKOWIAK 8. RATCLIFFE RS, RUDGE P. Late onset post-traumatic hypothalamic hypothermia. J Neurol Neurosurg Psychiatry 1983: 46: 7274. G, CAMBONH, DORMONT D, RICHARDA, 9. GAYMARD
DEROUESNE C. Hypothermia in a mesodiencephalic haematoma. J Neurol Neurosurg Psychiatry 1990: 53: 10141015. 10. BRANCHEF, BURGERPC, BREUVER DL. Hypothermia in
a case of hypothalamic infection and sarcoidosis. Arch Neurol 1971: 25: 245-255. 11. HARPERC. Wernicke’s encephalopathy: a more common disease than realised. A neuropathological study of 51 cases. J Neurol Neurosurg Psychiatry 1978: 42: 226-231. WC, SMYTHHS. 12. JAGADHA V, DECKJHN, HALLIDAY Wernicke’s encephalopathy in patients on peritoneal dialysis or hemodialysis. Ann Neurol 1987: 21: 78-84.
THIERAUFP, IGLESIAS J, 13. SCHWENKJ, GOSZTONYI, LANGERE. Wernicke’s encephalopathy in two patients with acquired immunodeficiency syndrome. J Neurol 1990: 237: 445 -447. 14. KAMALIAN. Lateral hypothalamic demyelination and cachexia in a case of malignant multiple sclerosis. Neurology 1975: 25: 25-30. 15. BIGNAMIA, GHERARDI D, DALLO G. Sclerosi a placche
acuta alocalizzazone ipotalamica con sintomatologica psichica di tip malinconico. Rivista di Neurologia 1961: 31: 240-268. 16. LUMSDEN CE. The neuropathology of multiple sclerosis. In:
VINKENPJ, BRUYNGW, eds. Handbook of clinical neurology. Amsterdam: Elsevier, 1965: 9: 217-309.
