[A study of bulbar, upper extremity, and lower extremity motor function preservation at the time that respiratory symptoms appear in ALS].

OBJECTIVE: To determine which of the three motor functions (bulbar, upper extremities, lower extremities) was normally preserved at the time that respiratory symptoms occurred in amyotrophic lateral sclerosis (ALS). BACKGROUND: Respiratory failure is the major cause of death in ALS. The course of the disease progression to the onset of subjective respiratory symptom can vary from patient to patient and the diversity of this progression in ALS patients is not well understood. PATIENTS/METHODS: The subjects were 120 Japanese patients with sporadic ALS who were followed-up at our hospital or for whom precise information was available regarding death or the time that the patient required tracheotomy or ventilation assistance. Symptoms started: in the upper limbs in 47 patients; in the lower limbs in 44 patients; in the bulbar region in 22 patients; as the combined type (two regions involved simultaneously on initial presentation) in 6 patients; and with respiratory symptoms in 1 patient. RESULTS: At the time of the appearance of respiratory symptoms, 43 patients (35.8%) had some normally preserved motor function. Significantly fewer patients with progressive bulbar palsy maintained one or more normal motor functions (14%) compared to patients whose disease started in the extremities (43%). Patients were divided into two groups depending on whether they had significant bulbar involvement at the time of the appearance of respiratory symptoms: 88 patients had significant bulbar involvement (B type), and 32 patients did not (R type). Based on the Kaplan-Meier survival curves, no significant difference in the median survival time was noted between the two groups (R type, 29.4 months vs. B type, 32.5 months; p = 0.06). We could not find any difference about clinical characteristics such as gender, onset age, initial site between R and B group. The motor functions that were preserved at the time of respiratory symptom onset included: bulbar function in 32 patients (26.7%); lower extremity function in 12 patients (10%); and upper extremity function in only 3 patients (2.5%). The use of mechanical ventilation in ALS patients with one or more preserved motor functions was significantly higher than in those without any normally preserved motor function (p = 0.03). CONCLUSIONS: From a low rate of upper extremity motor function preservation, respiratory function deterioration appears to be related to upper-limb involvement, likely due to a possible link to diaphragmatic function. Advanced directives should carefully address the use of mechanical ventilation in patients without bulbar symptoms.

Hypertensive brainstem encephalopathy without parieto-occipital lesion--two case reports.

Two patients presented with malignant hypertension associated with encephalopathy predominantly manifesting as brainstem lesion. T(2)-weighted and fluid-attenuated inversion recovery magnetic resonance (MR) imaging revealed diffuse hyperintense areas in the pons and scattered lesions in the cerebellum, basal ganglia, and cerebral subcortex without parieto-occipital lesions. Diffusion-weighted MR imaging demonstrated these lesions as normal intensity, indicating vasogenic edema. These lesions resolved rapidly once hypertension was controlled. Review of clinical findings for 14 other patients with hypertensive brainstem encephalopathy without parieto-occipital lesions suggested that anterior circulation structures supplied by the carotid artery are frequently involved in such patients.

[The changes of clinical characteristics in 100 Japanese amyotrophic lateral sclerosis patients between 1980 and 2000].

OBJECTIVE: To define changes of clinical features in amyotrophic lateral sclerosis (ALS) over the past 20 years and prognostic indicators of ALS from a single hospital-based retrospective survey. BACKGROUND: One of the important tasks in ALS research is to determine differences between patients who progress at different rates. Predicting survival time in ALS helps both physicians and patients to make decisions regarding assisted ventilation. PATIENTS/METHODS: A total of 100 patients (61 men, 39 women) hospitalized between 1980 and 2000 were investigated in the study. Subjects were divided into Groups A and B (Group A: n = 50, diagnosed between 1990 and 2000; Group B: n = 50, diagnosed between 1980 and 1990). Group C comprised 34 patients supported by artificial ventilation between 1980 and 2000. Information was obtained for all patients regarding time of individual primary end-point (PEP, time of death or required ventilation support), secondary end-point (SEP, time of death after artificial ventilation) or being alive with or without ventilation support. Combined type of ALS was defined as two or more regions presenting simultaneously at initial onset. Progression rate was calculated as the time (months) required for a 1-point loss on the ALS functional rating scale (ALS-FRS), using 1/delta FS:1/delta FS = duration (months) from onset to diagnosis/(48-ALSFRS at diagnosis) RESULTS: Mean age at onset has increased in the past 20 years from 59.4 years (group B) to 62.5 years (group A). An increased incidence has been observed in the patients over 70 years with ALS (A:n = 8 vs. B:n = 4). The frequency of assisted ventilation support had been significantly increased for 22 of 44 group A patients (50%) including 5 patients supported by non-invasive positive pressure ventilation, compared to 12 of 48 group B patients (25%, P < 0.01). Two patients in group B and 6 patients in group A who were still alive at time of the investigation were excluded. Mean interval between symptom onset and diagnosis was 14.7 months (A:14.0 months; B:15.4 months). No differences were observed between groups A, B and C regarding sex ratio, mean total ALS-FRS score at diagnosis. Mean survival times were as follows obtained from Kaplan-Meier survival curves; group A:30.8 months, group B:31.0 months until the time of PEP, group C:67.2 months until the time of SEP. Symptoms started in the upper limbs (U) in 37 patients, in the lower limbs (L) in 34, in the bulbar region (B) in 19, as combined type in 9 and in respiratory muscles in 1. Mean survival time until PEP was 33.9 months for U, 34.8 months for L, 28.6 months for B and 18.2 months for C (P < 0.001). Combined-type patients with ALS revealed shorter the time until diagnosis (*P < 0.01) and faster the time until PEP than the other ALS types (P < 0.001 Log-rank test). A significant correlation was found between 1/delta FS and the time until PEP (y = 9.64x + 12.6, r2 = 0.545, p < 0.001, y = PEP, x = 1/delta FS). CONCLUSIONS: Combined type ALS displayed significantly shorter time to PEP than other types. ALS outcome was significantly related to the progression rate of symptoms from total score for ALS-FRS at time of diagnosis.