Clinic and neuropathology

Insomnia is the prevailing symptom, and in the later stages followed by dream episodes more frequent with recited dreams. The development is towards astonishment and coma.
The autonomic dysautonomia is early with sphincter disturbances, salivation, lachrymation, constant sweating, runny nose, increased body temperature, heart rate (fixed tachycardia) and blood pressure. Breathing is particularly compromised, especially in advanced stages with tachypnea, irregular rhythm and depth of breathing, snoring and sleep apnea become more frequent and threatening, that border in asphyxiation. The patient, after a prolonged apnea, becomes cyanotic and at the peak of the respiratory pause, he wakes up suddenly, he leaps sitting, bathed in sweat, in anguish, he is alert. The motor manifestations include progressive difficulty in articulationg the words, until the inability to produce phonemes, dysphagia, dysmetria, and ataxic gait with retropulsion that results in astasia-abasia. There may be paresis of various segments of the body, usually a emisoma. Myoclonus, spontaneous or evoked, partial or massive, is absent at the beginning, but it appears quickly and it is intensified by the closing of the eyes. Osteotendinous hyperreflexia and the presence of the Babinski sign are invariably present. Ocular signs are miotic pupils and diplopia. The peculiar and serious disturbances of sleep architecture were confirmed by repeated neurophysiological studies. These show that the FFI present significant and worsening sleep alterations, which consist of a marked reduction of its total time until the complete loss. Progressive disappearance of NREM stages, deconstruction of sleep-wake rhythm, sudden burst of abnormal REM episodes dissolve the texture of sleep. The abnormalities extend to other fundamental bio-rhythms, as has been demonstrated by neurovegetative studies: cronic increase in sympathetic activity, high levels of cortisol and adrenaline, loss of circadian fluctuations of blood pressure and heart rate. These abnormalities worsen with the progression of the disease. The studies of neuropsychology have shown that there is not dementia. There is, however, an increasingly marked impairment in verbal memory and long term memory. The neuropathological studies have localized the most important lesions in the thalamus and more specifically in the anterior-ventral nucleus and in the dorsal-medial one. The elective thalamic involvement has been confirmed also by PET, which has documented the marked hypometabolism, associated with a less severe cortical hypometabolism. The damage is characterized by a serious neuronal loss and reactive astrogliosis. Minor injuries are present also in other brain regions such as the cortex and the olivary system. There may be spongiosis. These topographies have been identified in cases of disease of longer duration (25-33 months) than those exclusively thalamic which concern the short-term cases (8-9 months). The cortical lesions should be considered in relation to the trans neuronal damage due to the deafferentation, the cortex being the main target of the thalamic degeneration. The olivary structures could be damaged primitively. They receive afferents mainly from the spinal cord and less from the midbrain, and these systems result unharmed.