Central Pontine Myelinolysis Robert 0. Levitt, M.D., F.A.C.P. and David M. Shenker, M.D. With the acceptance of alcoholism as a disease, many previously obscure ailments are being recognized, among them, central pontine myeiinoiysis. This case report reviews the diagnostic criteria and methods used in reverslng the usual morbid outcome.
59-year-old, white female was hospitalized A with a 3-day history of tremors, generalized weakness, incontinence, and episodic vomiting. She admitted to excessive alcohol intake for the past 5 yr, culminating in a 3-wk treatment period in an alcohol rehabilitation unit. After maintaining sobriety for 5 mo, she then resumed her usual intake of whiskey (1 pint daily). She had been abstinent for 5 days and had not eaten for 3 days prior to hospital admission because of nausea and vomiting. There was a history of radical mastectomy for carcinoma 2 yr before this admission. Recent studies had failed to reveal any evidence of recurrence or metastases. She smoked one-half package of cigarettes daily. There was no family history of neurologic disease. The initial examination revealed a thin, anxious patient with coarse tremors of the upper extremities. Temperature was 99.5OF, blood pressure 110/70 mm Hg, pulse rate 116/min, and a respiratory rate of 15/min. Laboratory values included a WBC count of 6900/cu mm with 76% neutrophils, 1% band forms, 18% lymphocytes, 4% monocytes, and 1%eosinophils; RBC 4.95 million; hemoglobin 15.9 mg/dl; hematocrit 47.6; mean corpuscular volume (MCV) 97, mean corpuscular hemoglobin (MCHb) 32.8; mean corpuscular hemoglobin concentration (MCHC) 34.2. Urinalysis showed a specific gravity of 1.009, no glucose or protein, 2-4 WBC/high power field (HPF), and 0-1 RBC/HPF. Serum glucose was 206 mg/dl, blood urea nitrogen (BUN) 20 mg/dl, bilirubin 2.1 mg/dl, alkaline phosphatase 50 mU/ml, lactic dehydrogenase (LDH) 269 mU/ml, SGOT 100 mU/ml, calcium 10.7, phosphorus 2.7. Chest x-ray was normal. The initial treatment consisted of chlordiazepoxide for withdrawal symptoms, intravenous glucose and saline for dehydration, and vitamins. On the second hospital day, the tremulousness
had increased and slurring of her speech was noted. On the third day she became disoriented and refused to eat or drink. Gradual unresponsiveness to painful stimuli was noted. The temperature rose to 10l°F, and rales were detected in the left lung base. On the fourth hospital day, a spinal puncture was performed. The opening pressure was normal, there were 2 RBC/cu mm; 0 WBC/cu mm. The glucose was 59 mg/dl, and the protein 34 mg/dl. A chest x-ray revealed bilateral pulmonary infiltrates. Intravenous Keflin was begun. The patient’s condition deteriorated in the ensuing days. She remained comatose with grimacing evident on deep painful stimulation, All limbs were flaccid, and no deep tendon reflexes could be elicited. The toes were nonreactive to plantar stimulation; full eye movements were present to doll’s eye maneuvers; the pupils were in mid-position and responsive to light. The fundi were normal. On the eighth hospital day, laboratory studies disclosed a bilirubin of 1.1 mg/dl, LDH 375 pU/dl, SGOT 145 mU/ml, calcium 7.6 mg/dl, phosphorus 2.9 mg/dl, and serum ammonia 46 pg/dl. The BUN was increased to 46 mg/dl. Blood cultures were negative for bacterial growth and sputum cultures negative for pathogens. Serial electrocardiograms remained unchanged. Because of periods of apnea interspersed with Cheyne-Stokes respiration, the patient was intubated and required assisted respiration with the MA-1 respirator. At this time an electroencephalogram showed low voltage, 8-9 Hz, rhythms with polymorphic delta activity bilaterally over the frontal regions. A brain scan and skull x-ray were normal. The subsequent course was one of gradual ~~~
From the Alcoholism Unii and Department of Neurology, Grant Hospital of Chicago, Chicago, Ill. Received for publication, June 19, 1978; revision, August 1 , 1978. Reprint requests should be addressed to David M. Shenker, M.D., 845 North Michigan Avenue, Suite 987W. Chicago, Ill. 6061 I . 0 1979 by Grune & Straiion. Inc. 0145-4008/79/0301401 7$01.00/0
Alcoholism: Clinical and Experimental Research. Vol. 3 , No. 1 (January), 1979
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clinical improvement. On the 11th hospital day the patient opened her eyes and smiled and moved her right side purposefully to stimulation. However, her muscles remained flaccid and a paucity of spontaneous movements was noted. By the 15th hospital day, purposeful movements had increased, and the patient began to utter occasional words. Diffuse muscle weakness with hypotonia, wasting of the interossei of the hands and bilateral foot drop were noted. The deep tendon reflexes were more active on the right side and the Babinski signs equivocal. Pain sensation was intact, position and vibratory sensation moderately decreased in the lower extremities. A resting tremor was present in the upper extremities, which increased with intentional movement. Electromyographic studies were compatible with a sensorimotor peripheral neuropathy affecting both the upper and lower extremities with more advanced changes in the latter. A demyelinating process with minimal axonal degeneration of the right peroneal nerve appeared to be present. On the tenth day after instituting assisted respiration, the patient recovered her ability to breathe spontaneously and was weaned from the respirator. She subsequently became fully alert, oriented, and able to speak, swallow and care for herself. There remained a residual peripheral neuropathy of the lower extremities that required the use of short leg braces for ambulation. One year after the onset of this illness, the patient shows no signs of impaired mentation, but has an amnesia surrounding most of the events of her illness. She is gainfully employed, but still requires leg braces for ambulation because of persistent foot drop. DISCUSSION
In 1959, Adams et al.’ first described the entity of central pontine myelinolysis (CPM) in which patients presented with quadriparesis, lower cranial nerve dysfunction, and alterations in their state of consciousness. Pathologic changes consisted of a clearly defined area of myelin destruction in the rostra1 pons with relative sparing of axis cylinders and neurons. While the three patients described were chronic alcoholics and the disease has since been most frequently described in this type of patient, it has also been associated with general debility and
several systemic illnesses, including sarcoidosis, tuberculosis, and malignancies of the lymphoreticular system. In addition, as a diagnosis of CPM is frequently made only post mortem, numerous cases undoubtedly go unrecognized. While the implication has been that CPM is an almost invariably fatal disease, the difficulty in making this diagnosis must leave this point in question. Indeed, Wiederholt et al.* have recently described three patients with an illness they felt to clinically be CPM, two of whom survived with minimal neurologic deficits. We believe that at least a portion of our patient’s acute neurologic illness may have been due to CPM. In addition, there was evidence of an acute peripheral neuropathy. Several factors may have been important, namely the patient’s overall debility, dehydration, the acute pneumonitis, and chronic alcoholism. Interestingly enough, the third patient of Adams et a1.l also had evidence of neurologic symptoms and signs that appeared to be secondary to a peripheral neuropathy. In addition, at postmortem the characteristic pathologic findings of CPM were evident. Despite the above careful pathologic studies, the etiology of CPM must remain uncertain for the moment, and hypotheses, such as that of Vogel’ (that CPM may arise from a deficiency of some as-yet-unidentified substance or vitamin) remain untested. SUMMARY
A patient is reported whose ailment meets the criteria of CPM. The illness was complicated by pneumonitis, most likely of the aspiration type. Of particular interest was the reversibility of a clinical picture of marked deterioration when attention was paid to fluid and electrolyte balance and maintenance of respiration. This patient’s illness appears to meet the criteria of CPM, namely impairment of the facial muscles and tongue with dysphagia and dysarthria, flaccid quadriparesis or quadriplegia, and frequently, lack of response to painful stimuli followed by respiratory paraly~is.~ The presence of a peripheral neuropathy has been previously noted in a patient with CPM, but it is not an integral part of the disease. REFERENCES I . Adams RD, Victor M, Mancall E L Central pontine myelinolysis: A hitherto undescribed disease occurring in
CENTRAL PONTINE MYELINOLYSIS
alcoholic and malnourished patients. Arch Neurol Psychiatry 81:154-172, 1959 2. Wiederholt WC, Kobayashi RM, Stockard JJ, Rossiter VS: Central pontine myelinolysis. Arch Neurol 34:220-223, 1977
85
3. Vogel FS: Concerning the pathogenesis of central pontine myelinolysis and Wernicke’s encephalopathy, associates of chronic alcoholism. Alcoholism 1:67-72, 1977 4. Drumus PM: Central pontine myelinolysis, in Beeson PB, McDermott W ( 4 s ) : Textbook of Medicine. Philadelphia, Saunders, 1975. p 71 3
59-year-old, white female was hospitalized A with a 3-day history of tremors, generalized weakness, incontinence, and episodic vomiting. She admitted to excessive alcohol intake for the past 5 yr, culminating in a 3-wk treatment period in an alcohol rehabilitation unit. After maintaining sobriety for 5 mo, she then resumed her usual intake of whiskey (1 pint daily). She had been abstinent for 5 days and had not eaten for 3 days prior to hospital admission because of nausea and vomiting. There was a history of radical mastectomy for carcinoma 2 yr before this admission. Recent studies had failed to reveal any evidence of recurrence or metastases. She smoked one-half package of cigarettes daily. There was no family history of neurologic disease. The initial examination revealed a thin, anxious patient with coarse tremors of the upper extremities. Temperature was 99.5OF, blood pressure 110/70 mm Hg, pulse rate 116/min, and a respiratory rate of 15/min. Laboratory values included a WBC count of 6900/cu mm with 76% neutrophils, 1% band forms, 18% lymphocytes, 4% monocytes, and 1%eosinophils; RBC 4.95 million; hemoglobin 15.9 mg/dl; hematocrit 47.6; mean corpuscular volume (MCV) 97, mean corpuscular hemoglobin (MCHb) 32.8; mean corpuscular hemoglobin concentration (MCHC) 34.2. Urinalysis showed a specific gravity of 1.009, no glucose or protein, 2-4 WBC/high power field (HPF), and 0-1 RBC/HPF. Serum glucose was 206 mg/dl, blood urea nitrogen (BUN) 20 mg/dl, bilirubin 2.1 mg/dl, alkaline phosphatase 50 mU/ml, lactic dehydrogenase (LDH) 269 mU/ml, SGOT 100 mU/ml, calcium 10.7, phosphorus 2.7. Chest x-ray was normal. The initial treatment consisted of chlordiazepoxide for withdrawal symptoms, intravenous glucose and saline for dehydration, and vitamins. On the second hospital day, the tremulousness
had increased and slurring of her speech was noted. On the third day she became disoriented and refused to eat or drink. Gradual unresponsiveness to painful stimuli was noted. The temperature rose to 10l°F, and rales were detected in the left lung base. On the fourth hospital day, a spinal puncture was performed. The opening pressure was normal, there were 2 RBC/cu mm; 0 WBC/cu mm. The glucose was 59 mg/dl, and the protein 34 mg/dl. A chest x-ray revealed bilateral pulmonary infiltrates. Intravenous Keflin was begun. The patient’s condition deteriorated in the ensuing days. She remained comatose with grimacing evident on deep painful stimulation, All limbs were flaccid, and no deep tendon reflexes could be elicited. The toes were nonreactive to plantar stimulation; full eye movements were present to doll’s eye maneuvers; the pupils were in mid-position and responsive to light. The fundi were normal. On the eighth hospital day, laboratory studies disclosed a bilirubin of 1.1 mg/dl, LDH 375 pU/dl, SGOT 145 mU/ml, calcium 7.6 mg/dl, phosphorus 2.9 mg/dl, and serum ammonia 46 pg/dl. The BUN was increased to 46 mg/dl. Blood cultures were negative for bacterial growth and sputum cultures negative for pathogens. Serial electrocardiograms remained unchanged. Because of periods of apnea interspersed with Cheyne-Stokes respiration, the patient was intubated and required assisted respiration with the MA-1 respirator. At this time an electroencephalogram showed low voltage, 8-9 Hz, rhythms with polymorphic delta activity bilaterally over the frontal regions. A brain scan and skull x-ray were normal. The subsequent course was one of gradual ~~~
From the Alcoholism Unii and Department of Neurology, Grant Hospital of Chicago, Chicago, Ill. Received for publication, June 19, 1978; revision, August 1 , 1978. Reprint requests should be addressed to David M. Shenker, M.D., 845 North Michigan Avenue, Suite 987W. Chicago, Ill. 6061 I . 0 1979 by Grune & Straiion. Inc. 0145-4008/79/0301401 7$01.00/0
Alcoholism: Clinical and Experimental Research. Vol. 3 , No. 1 (January), 1979
83
LEVITT AND SHENKER
84
clinical improvement. On the 11th hospital day the patient opened her eyes and smiled and moved her right side purposefully to stimulation. However, her muscles remained flaccid and a paucity of spontaneous movements was noted. By the 15th hospital day, purposeful movements had increased, and the patient began to utter occasional words. Diffuse muscle weakness with hypotonia, wasting of the interossei of the hands and bilateral foot drop were noted. The deep tendon reflexes were more active on the right side and the Babinski signs equivocal. Pain sensation was intact, position and vibratory sensation moderately decreased in the lower extremities. A resting tremor was present in the upper extremities, which increased with intentional movement. Electromyographic studies were compatible with a sensorimotor peripheral neuropathy affecting both the upper and lower extremities with more advanced changes in the latter. A demyelinating process with minimal axonal degeneration of the right peroneal nerve appeared to be present. On the tenth day after instituting assisted respiration, the patient recovered her ability to breathe spontaneously and was weaned from the respirator. She subsequently became fully alert, oriented, and able to speak, swallow and care for herself. There remained a residual peripheral neuropathy of the lower extremities that required the use of short leg braces for ambulation. One year after the onset of this illness, the patient shows no signs of impaired mentation, but has an amnesia surrounding most of the events of her illness. She is gainfully employed, but still requires leg braces for ambulation because of persistent foot drop. DISCUSSION
In 1959, Adams et al.’ first described the entity of central pontine myelinolysis (CPM) in which patients presented with quadriparesis, lower cranial nerve dysfunction, and alterations in their state of consciousness. Pathologic changes consisted of a clearly defined area of myelin destruction in the rostra1 pons with relative sparing of axis cylinders and neurons. While the three patients described were chronic alcoholics and the disease has since been most frequently described in this type of patient, it has also been associated with general debility and
several systemic illnesses, including sarcoidosis, tuberculosis, and malignancies of the lymphoreticular system. In addition, as a diagnosis of CPM is frequently made only post mortem, numerous cases undoubtedly go unrecognized. While the implication has been that CPM is an almost invariably fatal disease, the difficulty in making this diagnosis must leave this point in question. Indeed, Wiederholt et al.* have recently described three patients with an illness they felt to clinically be CPM, two of whom survived with minimal neurologic deficits. We believe that at least a portion of our patient’s acute neurologic illness may have been due to CPM. In addition, there was evidence of an acute peripheral neuropathy. Several factors may have been important, namely the patient’s overall debility, dehydration, the acute pneumonitis, and chronic alcoholism. Interestingly enough, the third patient of Adams et a1.l also had evidence of neurologic symptoms and signs that appeared to be secondary to a peripheral neuropathy. In addition, at postmortem the characteristic pathologic findings of CPM were evident. Despite the above careful pathologic studies, the etiology of CPM must remain uncertain for the moment, and hypotheses, such as that of Vogel’ (that CPM may arise from a deficiency of some as-yet-unidentified substance or vitamin) remain untested. SUMMARY
A patient is reported whose ailment meets the criteria of CPM. The illness was complicated by pneumonitis, most likely of the aspiration type. Of particular interest was the reversibility of a clinical picture of marked deterioration when attention was paid to fluid and electrolyte balance and maintenance of respiration. This patient’s illness appears to meet the criteria of CPM, namely impairment of the facial muscles and tongue with dysphagia and dysarthria, flaccid quadriparesis or quadriplegia, and frequently, lack of response to painful stimuli followed by respiratory paraly~is.~ The presence of a peripheral neuropathy has been previously noted in a patient with CPM, but it is not an integral part of the disease. REFERENCES I . Adams RD, Victor M, Mancall E L Central pontine myelinolysis: A hitherto undescribed disease occurring in
CENTRAL PONTINE MYELINOLYSIS
alcoholic and malnourished patients. Arch Neurol Psychiatry 81:154-172, 1959 2. Wiederholt WC, Kobayashi RM, Stockard JJ, Rossiter VS: Central pontine myelinolysis. Arch Neurol 34:220-223, 1977
85
3. Vogel FS: Concerning the pathogenesis of central pontine myelinolysis and Wernicke’s encephalopathy, associates of chronic alcoholism. Alcoholism 1:67-72, 1977 4. Drumus PM: Central pontine myelinolysis, in Beeson PB, McDermott W ( 4 s ) : Textbook of Medicine. Philadelphia, Saunders, 1975. p 71 3
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