Caso clínico Masculino de 61 años de edad

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HISTORICAL BACKGROUND — In 1964, Steele, Richardson, and Olszewski were the first to describe PSP when their seminal report of nine cases with autopsy confirmation was published [1]. As a result of their pioneering work, some have referred to the disease as the Steele-Richardson-Olszewski syndrome. Since that time, hundreds of additional cases have been recorded, and the disease is now a well-recognized atypical parkinsonian syndrome (or Parkinson-plus disorder). As originally described, PSP is characterized by progressive supranuclear ophthalmoplegia, gait disorder and postural instability, dysarthria, dysphagia, rigidity, and frontal cognitive disturbance. The authors of the original report speculated whether PSP was a primary disorder of the central nervous system or a postinfectious (viral) syndrome [2]. The consistent pathologic features of PSP consist of neuronal loss, globose neurofibrillary tangles, and gliosis mainly in the basal ganglia, cerebellum, brainstem, and to a lesser extent, the cerebral cortex [3]. A universally accepted set of diagnostic criteria for PSP was proposed in 1996 [4]. (See 'Diagnostic criteria' below.)

PSP is now recognized to encompass a number of phenotypic variants. The two most common are Richardson syndrome (the classic form of PSP) and PSP-parkinsonism.

EPIDEMIOLOGY — PSP is the most common of the degenerative forms of atypical parkinsonism [5,6]. An early study found that the population prevalence of PSP was 1.39 per 100,000 in the United States [7]. Although this study has been criticized because of methodologic flaws, it established that PSP was not as rare as had previously been believed. Later reports from other countries demonstrated an even higher prevalence, 6.4 per 100,000 in the United Kingdom [6,8] and 5.8 per 100,000 in western Japan [9].

Early studies found that the annual incidence rates of PSP ranged from 0.3 to 0.4 per 100,000 [10-12]. However, a study published in 1999 reported an annual incidence of 1.1 per 100,000 [5,13]. The greater incidence found in later studies may be a result of better case ascertainment due in part to increased recognition of the disorder [5]. The annual incidence increases with age from 1.7 cases per 100,000 at ages 50 to 59 years to 14.7 per 100,000 at 80 to 89 years [14]. The true incidence may be higher still with the subsequent discovery that several phenotypes of PSP exist. (See 'Variant phenotypes' below.)

The mean age of onset for PSP is approximately 62 years [7,15], which is older than in idiopathic Parkinson disease. Virtually no cases of PSP have been reported in patients younger than age 40 [2]. The original clinical report noted a strong male predominance of approximately eight to one [1]. However, later reports have been mixed. Six series found a male predominance, [2,7,16-19], two a female predominance, [15,20], and one an even ratio [21].

In a series of 121 patients with probable PSP, there were no significant male-female differences for a variety of disease measures including age at onset, clinical characteristics, and disease duration [22].

Risk factors — There are no proven risk factors for the development of PSP except age. Some studies have reported that education level or environmental exposures may be associated with increased risk, but the findings have been inconclusive. An early case-control study found that patients with PSP (n = 50) were more likely than controls to have completed high school and college [23]. However, a subsequent study from the same investigators with 113 patients found that lower levels of education were associated with an increased risk of PSP, whereas no history of elevated toxic exposure was detected [24].

A cluster of PSP cases in northern France was linked to potential exposure to industrial waste, specifically phosphate and chromate ore [25]. Two small case series reported environmental exposure to organic solvents in 12 of 13 patients with PSP [26,27]. Further studies are needed to determine if environmental toxins play a role in the pathogenesis of PSP.

Genetic susceptibility — Although PSP is considered to be a sporadic disorder, some observations suggest that genetic susceptibility has a role:

●There are a few reports of a positive family history of PSP and other types of parkinsonism [28-30]. However, these are distinctly rare.

●A genome-wide association study reported an increased risk of PSP for two independent variants of microtubule-associated protein tau gene (MAPT) [31]. In addition, the study found an increased risk for several additional genes (STX6, EIF2AK3, and MOBP), the significance of which is unclear.

●Several studies have demonstrated an overrepresentation of the H1 haplotype and A0 allele of the MAPT in PSP [32-34]. This has implied biological plausibility, since the tau protein is abundant in the brains of subjects with PSP. However, the H1 haplotype is also more common in patients with Parkinson disease compared with controls, even though tau accumulation and aggregation is not a part of the pathological picture of Parkinson disease [35]. Hence, the meaning of this finding still needs to be clarified.

●A case-control study reported that first-degree relatives of patients with PSP performed worse than normal controls on an idiopathic Parkinson disease test battery that evaluated motor function, olfaction, and mood [36]. The authors speculated that testing may detect an asymptomatic carrier state or risk for PSP, or a subclinical effect of a shared environmental exposure.

CLINICAL CHARACTERISTICS — With the most common "classic" phenotype of PSP, known as Richardson phenotype or Richardson syndrome, the most frequent initial feature of PSP is a disturbance of gait resulting in falls. Supranuclear ophthalmoparesis or plegia is the hallmark of PSP (hence the name of the disease). Dysarthria, dysphagia, pseudobulbar palsy, rigidity, frontal cognitive abnormalities, and sleep disturbances are additional common clinical features.

Postural instability and falls — Patients with classic PSP have a stiff and broad-based gait, with a tendency to have their knees and trunk extended (as opposed to the flexed posture of idiopathic Parkinson disease), and arms slightly abducted. They demonstrate impulsivity, probably from the frontal lobe involvement, and hence tend to lurch and stagger. Step length is varied, as is base width. Instead of turning en bloc as seen in Parkinson disease, they tend to pivot quickly, further compromising their balance and indicating an inability to take protective measures. When they fall, it is usually backwards. Over the course of the illness, such

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