Beneficial effect of propranolol in familial ataxia

Abstract

Intention tremor, attributed to defective function of the cerebellum or its connections. is generally not amenable to medication. Although different in character from the rhythmic low-amplitude oscillations of essential tremor, favorable reports of the effectiveness of propranolol in the latter disorder [2] prompted us to try this drug on 2 brothers suffering from cerebellar ataxia.A 27-year-old serviceman, the son of a first-cousin marriage, was examined five years ago because of a disturbance in speech and loss of upper limb control first noted about a year previously. H e was markedly dysarthric and voluntary movements of the upper limbs were grossly affected by intention tremor, worse on the left. Ataxia of gait was only slight. Tendon reflexes were absent and the limbs were hypotonic. Corneal telangiectasia was not seen, nor were there any skeletal abnormalities. Laboratory investigations were normal.During the next two years his condition deteriorated; he had to drink from the tap-being unable to bring a tumbler to his mouth without spilling the contents-and ate by lowering his head to the plate. Treatment with propranolol. 40 mg three times a day, was begun with immediate benefit in motor performance and clarity of speech. When treatment was stopped two months later, the patient reverted to the previous state. Improvement followed reinstitution of therapy; a year later, a second temporary attempt to stop the drug resulted again in deterioration.Recently, the 19-year-old brother of the patient was found to have similar symptoms and signs. Again, function was grossly impaired in the upper limbs with marked intention tremor. Speech was notably dysarthric, but walking was only moderately atactic. Hypotonia was noted, and tendon reflexes were absent; there was no nystagmus or sensory loss. Laboratory tests were all normal.Propranolol, 40 mg three times day, brought about marked improvement in function within 48 hours. Simple quantitative tests indicated a three-to four-fold improvement.I t would be fruitless to speculate o n the site of action of the propranolol in our patients. The drug is known to enter the brain readily, but its various effects are not believed to be due to a central action 131. However Tremorscheinungen und deren therapeutisches BeeinHussbarkeit. Med Welt 24:237-240, 1973 33~53-65, 1967 The Association and 13 S controls (medical students, secretaries, laboratory personnel) replied to a postcard questionnaire that requested information on residential location (town, suburb, o r rural) and type (house, apartment). and frequent and close exposure between the ages of 8 and 16 years to cats, dogs, horses, chickens, rabbits, and cows. The two groups were remarkably similar with respect to the background characteristics assessed; nearly all came from rural and semirural areas in Vermont, Massachusetts, and northeastern New York.The Table compares the MS and control groups. The chi-square values demonstrate that previous exposure to cats, dogs (large or small), rabbits, and horses is not associa...

Adrenergic receptors in the cerebellum of olivopontocerebellar atrophy

“…Compounds acting on noradrenergic receptors have shown positive effects on some human disorders involving" the cerebellum. For instance, propranolol, a ]3-adrenergic blocker has been reported as improving several clinical aspects of familial and sporadic ataxic syndromes (Braham et al, 1979;Duhigg, 1985). Taking our findings into account, in these cases propranolol could potentially exert its beneficial effects by counteracting the here observed increase in noradrenergic tone secondary to both the increase in ~2 receptors and the loss of the inhibitory alpha2-adrenoceptors.…”

Propranolol Modulates Cerebellar Circuit Activity and Reduces Tremor

“…Previous studies have also examined the effects of propranolol in human patients with ataxia and dystonia, which is interesting given the potential common origins of these diseases from within the cerebellum. Propranolol was found to temporarily alleviate ataxia in a few clinical reports [ 103 , 104 ]. Additionally, differential effects of propranolol were found in patients with comorbid dystonia and tremor, suggesting that at least some aspects of the pathophysiology underlying these two conditions are distinct [ 105 ].…”

Mitochondrial iron and calcium homeostasis in Friedreich ataxia

“…Indeed, the patient, which heart was used for necropsy by Barbeau was treated with propranolol. While an early study showed a beneficial effect in motor performance and speech for propranolol, 70 it was in 2005 that a study with high doses of propranolol showed reduction in the thickness of the septal and posterior left ventricular walls 69 . At cellular level, calcium is an important signaling molecule, from contractibility of muscle cells to excitability of neurones but also for cellular migration and growth.…”