Historically, the prognosis in CPM or CPEPM has been considered very poor. More recent studies (primarily retrospective chart reviews), however, indicate a considerable range in both clinical course and prognosis in patients with clinically symptomatic CPM and/or CPEPM.14,25–27 The first of these studies examined 44 cases, most (42/44) with chronic alcoholism.25 Of the 32 patients with follow-up data who survived (2 died in the acute phase), 34% (11/32) had a “good outcome” (no significant functional deficits); 34% (11/32) had an “adequate outcome” (minor neurological deficits); and 31% (10/32) had a “poor outcome” (dependent). Another study in patients with alcoholism reported somewhat more favorable outcomes, with 44% (4/9) free of neurological deficits by 6 months after onset.26 The authors noted that most of their cohort (8/9) did not have an episode of acute correction of hyponatremia. A more recent study examined 12 individuals with CPEPM related to a variety of medical causes.14 In this more-diverse population, four patients died in the acute phase, and two were lost to follow-up. The remaining six were reported to have “good motor and cerebellar recovery.” However, all five of the patients who received neuropsychological testing had evidence of subcortical/frontal dysfunction, and most of these (4/5) were unable to return to work. The most recent study is also the only one to include prospective collection of objective follow-up measures of disability and functional status.27 As in the previous study, this cohort was quite diverse in terms of causative conditions. Almost half (12/25) died either during the acute phase (2) or after hospital discharge (10). One was lost to follow-up. At final follow-up (mean 2.2 years; median: 1 year; range: 0–8 years), 29% (7/24) were normal; 17% (4/24) had mild cognitive or extrapyramidal deficits; and 54% (13/24) had a poor outcome (died or were dependent). Univariate analysis indicated that lower initial Glasgow Coma Scores, lower disability rating scales, lower sodium levels, and the presence of hypokalemia all predicted poorer outcomes. Although these studies differ in many respects, some consistent themes are emerging. A common pattern is an initial presentation with delirium, seizures, or encephalopathy, followed by a brief period (i.e., a few days) of lucidity or clarity before the onset of symptoms indicating CPEPM. These studies indicate that a “favorable” prognosis is possible, although few return to previous levels of functioning. The authors of one study made an interesting proposal, based on their results combined with data from previous publications, delineating three groups of patients with distinguishable prognoses.14 Group One included patients who present with seizures and have a “good” prognosis. Group Two included those with cerebellar presentations (i.e., commonly, with severe alcoholism). These patients generally have good physical recovery, with residual cognitive impairment. Group Three comprised those with immunosuppression and liver transplantation. These patients generally present with more severe clinical features and do very poorly. This three-part grouping is in reasonable agreement with the prognostic factors noted above.27
The literature contains only a few reports of neuropsychological test results in cases of CPM and/or EPM. Two case reports included test results within 2 weeks of symptom onset.28,29 A patient with only EPM (lesions in the basal ganglia) had severely impaired attention, verbal and visual memory, visuospatial function, frontal executive function, recognition memory, free recall memory, and naming, with preservation of other language-related functions.29 All these deficits are consistent with previous reports in patients with basal ganglia lesions. In the other case, the patient had CPEPM (lesions in the pons, caudate, lentiform nucleus, thalamus, and internal capsules).28 At 1 week, the patient had prominent deficits in attention and concentration (e.g., high distractibility, slow visual scanning), memory (immediate verbal recall and memory for daily events), visuomotor functioning, and fine motor speed. On reexamination at 4 months, the patient had improved somewhat in some domains, but deficits were still clearly present, and new problems included learning of new verbal information. Although acute neurological and behavioral symptoms had resolved, a new vocal tremor was present. Two other studies included neuropsychological test results obtained 1 month or more after symptom onset. A case report of CPM after liver transplantation noted lower-than-expected intellectual abilities, impairments of attention (auditory, divided, and selective), learning, problem-solving, and ability to use feedback to alter action, as well as pathological crying and laughter at 6 months after symptom onset, all consistent with a brainstem process.30 Finally, in a case series described above, follow-up of five patients included neuropsychological testing (range: 1–19 months after onset of symptoms).14 Although details of measures and scores are not provided, all five were noted to have subcortical/frontal dysfunction, and memory was impaired in two. Some of the patients in these studies had histories of alcoholism before CPM, possibly affecting the test results. Overall, although limited neuropsychological information is available in patients with CPM or CPEPM, many patients have lasting and significant cognitive impairments consistent with other pathological insults to the brainstem or subcortical structures.