Central pontine myelinolysis in a case of alcohol dependence syndrome.

Osmotic Demyelination Syndrome includes Central Pontine Myelinolysis and Extrapontine Myelinolysis. This condition has been described in cases of chronic Alcohol Dependence Syndrome and in rapid correction of hyponatremia. Though we frequently see patients with Alcohol Dependence Syndrome presenting with complicated withdrawal, Central Pontine Myelinolysis remains largely undetected and under-reported in literature. We present here a case of protracted Delirium Tremens where MRI brain revealed Central Pontine Myelinolysis. Subsequently cognitive assessment revealed significant dysfunction and brain SPECT showed hypo-perfusion of the frontal lobes. Osmotic Demyelination Syndrome should be suspected in protracted Delirium Tremens.

Central pontine myelinolysis (CPM) was described in 1959 by Adams et al. as a condition seen in alcoholics and malnourished individuals which is a result of an osmotic insult and demyelination of the basis pontis.[1] This concept was extended in 1962 with the recognition that lesions can occur outside the pons, so-called extrapontine myelinolysis (EPM).[2] Chronic alcohol abuse appears to be a particular risk factor for CPM and EPM. It has been reported that chronic alcoholics may be asymptomatic or have relatively few symptoms, with a better outcome of their CPM and EPM than in cases associated with an acute correction of hyponatremia.[3]

Patients with chronic alcohol dependence are commonly given intravenous fluids as part of the treatment of alcohol withdrawal. They are predisposed to chronic severe hyponatremia because of a variety of mechanisms including psuedohyponatremia, hypovolemia, cerebral salt wasting syndrome, and reset osmostat syndrome.[4]

Functional neuroimaging studies in recently detoxified alcoholics using positron emission tomography or single photon emission computed tomography (SPECT) revealed global reduced cerebral perfusion in frontal regions.[5] Frontal lobe dysfunctions are consistently described in chronic alcoholics.[6]

CASE REPORT

A 52-year-old male was admitted to medical ward for the management of a severe headache and raised blood pressure. Subsequently, he suffered a seizure and developed an irrelevant speech for which a psychiatric consultation was sought.

History revealed alcohol consumption from the age of 22 years. By the age of 45 years, he had features of alcohol dependence in the form of craving, tolerance, loss of control, withdrawal discomfort, the primacy of alcohol use, and sociooccupational deterioration. He consumed around 750 ml of rum daily. Before 2 days admission, he abruptly stopped drinking after repeated pleading by family members. He had been detected to have hypertension in 2007 and diabetes mellitus (Type II) along with dyslipidemia in 2008. There was no family history of mental illness or substance use. He is educated up to 9th class and has been employed for last 26 years. He chewed tobacco regularly for last 30 years.

He had tachycardia, raised blood pressure, bilateral coarse digital tremors, and diaphoresis. He was disoriented and had vivid visual and auditory hallucinations along with secondary delusions of persecution. There was no focal neurological deficit or neck rigidity. A urine drug screen was negative. Laboratory investigation findings are summarized in Table 1. A diagnosis of alcohol dependence syndrome (complicated withdrawal with seizures and delirium) was made, and the patient was treated with chlordiazepoxide in tapering doses, thiamine supplementation and parenteral haloperidol for behavioral control. His response to treatment was tardy and though his orientation improved he had difficulty in comprehending instructions even a week later. Mini- mental state examination (MMSE) score improved from 12 at admission to 26. However, he remained dull and was unable to participate in routine neurocognitive evaluation even a fortnight after admission. Progression of withdrawal and MMSE are described in Table 2.

Table 1

Laboratory investigations

Table 2

Alcohol Withdrawal Scale and mini-mental state examination scores

Contrast enhanced magnetic resonance imaging (MRI) brain done then, revealed a nonenhancing area of altered signal intensity in central pons suggestive of CPM [Figure 1]. Brain SPECT showed hypoperfusion of frontal lobes (L > R) but yielded no further information about the pons [Figure 2]. Electroencephalogram showed no abnormality. By the 3rd week, cognitive functions started improving, and he was co-operative. Evaluation of lifetime drinking history[7] yielded total alcohol consumption of 496.61 kg over 30 years, with an average drinking day consumption of 80.35 g/day. Repeated after 6 weeks, MRI showed a reduction in size of pontine lesion. Repeated after 8 weeks brain, SPECT showed improvement in frontal lobe perfusion [Figure 3]. Detailed neuropsychological evaluation done at 2, 6, and 10 weeks of admission is depicted in Table 3. Even though there was relative improvement in scores on neuropsychological evaluation in the 6th and 10th week, cognitive deficits remained.

Figure 1

Contrast enhanced magnetic resonance imaging of brain ill-defined area of altered signal intensity in central pons (7.0 mm × 6.7 mm × 8.1 mm). (a) Sagittal section postcontrast brain shows no postcontrast enhancement. (b) On fluid-attenuated inversion recovery it is hypo-intense. (c) On magnetic resonance imaging diffusion there is true restriction of diffusion on diffusion weighted imaging and apparent diffusion coefficient map

Figure 2

Initial brain single photon emission computed tomography hypoperfusion in frontal lobes (left hypoperfusion [15.96%] >right hypoperfusion [20.87%])

Figure 3

Repeat brain single photon emission computed tomography (8 weeks later). Mild hypo-perfusion in frontal lobes. Perfusion in frontal lobes (left [17.91%], right [22.24%]) is better than in previous scan

Table 3

Neuropsychological evaluation

DISCUSSION

Various mechanisms have been proposed for the development of osmotic demyelination following chronic alcohol use. Rapid correction of hyponatremia remains the most documented etiologic factor. Oligodendroglia are particularly susceptible to dehydration and volume changes due to their physically tight alignment in the basis pontis. During rapid correction of hyponatremia, intracellular electrolyte corrections are swift, but the brain is unable to correct the loss of organic osmolytes quickly enough, resulting in cellular dehydration, damage to the myelin sheath, and oligodendrocyte degeneration. The process of maintaining an iso-osmolar environment with respect to the serum is energy consuming. If the patient is malnourished, as is typically the case in alcohol dependence, the cells may lack sufficient energy reserve to maintain the Na+/K+ ATPase pump activity and to synthesize organic osmoles. Alcohol-associated thiamine deficiency may exacerbate the problem because it decreases brain glucose uptake. This energy supply–demand imbalance results in a pro-apoptotic drive.[8]

In this patient, no hyponatremia was detected, though he had been initially treated with intravenous Ringer's lactate in the medical ward for dehydration. After a protracted alcohol withdrawal, he manifested significant impairment in all cognitive domains which improved partially and gradually thereafter. This correlates with the findings of Mochizuki et al., that CPM due to alcohol use leaves neurological deficits.[5] Nicolás et al. found that two-thirds of patients of active chronic alcoholism exhibited frontal lobe impairment demonstrated by neuropsychological testing and SPECT, independent of brain atrophy.[9] Noël et al. reported that decreased blood flow in the inferior frontal gyrus assessed by SPECT was associated with executive function deficits which were related to relapse in detoxified alcohol-dependent individuals.[5]

Protracted delirium tremens is encountered frequently in patients of alcohol dependence syndrome. They should be investigated using neuroimaging and caution should be exercised while correcting their fluid and electrolyte imbalances.

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Conflicts of interest

There are no conflicts of interest.