Postgrad Med J: first published as 10.1136/pgmj.50.586.521 on 1 August 1974. Downloaded from Postgraduate Medical Journal (August 1974) 50, 521-523.

Treatment of blepharospasm with levodopa

N. K. CHAKRAVORTY M.B.B.S., M.R.C.P.(E.), D.T.M. & H.

St Luke's Hospital, Huddersfield

Mechanism of production of Parkinsonian symptoms prolonged use of phenothiazines or reserpine is The clinical features that result when the 'extra- seldom severe and very often is reversible. pyramidal' motor system is involved in disease are It is now recognized that reserpine will deplete often highly characteristic, but unfortunately not yet dopamine in the and produce parkin- well understood. Explanation of symptoms of sonism in man. The depletion of dopamine in the Parkinson's disease is difficult not only because of globus pallidus found at post mortem suggests that their complexity but also by difficulties in inter- an attempt to restore normal concentrations of preting the pathological material. There are few dopamine in the basal ganglia could be helpful in pathological changes, the most consistent appearing . Dopamine will not cross the blood to be the loss of nerve cells from the substantia nigra brain barrier, but levodopa (L-dopa) will, and has been found to be effective in controlling the symp- and of myelinated fibres from the globus pallidus Protected by copyright. and depletion of dopamine in the globus pallidus. toms of parkinsonism. It is possible that the symp- However, it is important that the clinical features are toms of parkinsonism arise in some way from loss recognized before attempts are made to understand of neurones in the substantia nigra that liberate the underlying mechanism of production of symp- dopamine as a transmitter substance in the globus toms in the light of present knowledge. pallidus, and that this is normally balanced by other One of the commonest and earliest symptoms of fibres liberating acetylcholine. parkinsonism is consisting of rhythmic It has been suggested that blepharospasm could be alternating movements of opposing muscle groups a nociceptive reflex normally inhibited by dopamine, with a frequency of about 6/sec. The tremor is usually and that this inhibition is lost in patients suffering confined to one hand or less commonly the foot and from parkinsonism. The loss is functional but can can spread with varying degrees of rapidity to the be corrected by dopamine acting in the striatum. other limbs, head and jaw. The tremor is present Klawans and Erlich (1970) suggest that blepharo- when the patient is at rest and is commonly sup- may be due to nociceptive reflex initiated by

pressed during voluntary movement. stimuli such as strong light, gusts of wind, cigarette http://pmj.bmj.com/ The major disability is disorder of voluntary move- smoke, etc. This closure is spontaneous and can vary ment, akinesia. This results in small and cramped from fibrillary twitching of a few fibres of the hand-writing, difficulty in fastening buttons and shoe orbicularis oculi to severe, prolonged and painful laces, difficulty in rising from a chair, slowness in contractions of both orbicularis muscles. walking, etc. Frequent falls are not uncommon. Three patients suffering from parkinsonism with Muscle rigidity is present except in the very early blepharospasm were treated with L-dopa. In all cases and can be demonstrated on passive flexion and three, there was considerable improvement in par- extension of the wrist or elbow. In parkinsonism, the kinsonism as well as blepharospasm, and in two on September 27, 2021 by guest. facial muscles exhibit an unnatural immobility. cases the blepharospasm was reversed within 4 weeks Depression also appears to be an integral symptom of starting treatment. In all three there was a re- of the disease. markable improvement in the depression. There are some characteristic features in post- encephalitic parkinsonism. The rigidity is dispro- Case 1 portionate in severity. Ocular symptoms and signs L.B. is a 70-year-old male with a 3-year history of are common. Blepharospasm may be severe enough parkinsonism. Initially, stiffness and slowness of to prevent useful vision. There may be oculogyric movements with masked facies were noted. Over crises. Pupillary abnormalities, ocular palsies and the last 2 years, he developed cogwheel rigidity, increased tendon jerks may also be present. It is now tremor of hands, difficulty in initiating movements, thought arterio-sclerosis plays no part in the aetiology shuffling gait and poor balance. Recently, difficulty of parkinsonism. Drug-induced parkinsonism due to in initiating and carrying out movements became so Postgrad Med J: first published as 10.1136/pgmj.50.586.521 on 1 August 1974. Downloaded from 522 Case reports much worse that he found it difficult to get out of a Neurological examination revealed the patient to chair and walk about inside the house and also he be very alert and well orientated with both recent and was having frequent falls. He was depressed. His remote memory intact. She was unable to rise by voice became weak and speech was low pitched and herself from a seated position. Deep tendon reflexes almost inaudible. For the last 3 months, he was were normal and symmetrical. Examination of having episodes of involuntary closure of both eyes cranial nerves and sensations revealed no abnor- associated with pain which was gradually getting mality. She was depressed. The features of parkin- worse. At times, he had to keep the eyes open sonism which were present are already mentioned. manually. When the eyelids were held open, vision Medication for the last few years was benzhexol, and extraocular movements were normal. orphenadrine and benztropine methanesulphonate, His past history includes a moderate hypertension imipramine (for depression) and amantidine for the (200/115 mmHg) but no . Neurological last year. She was started on a small dose of L-dopa, examination revealed that the patient was reasonably 250 mg b.d. which was gradually increased to a total alert. Cranial nerves, sensations and deep tendon daily dosage of 2 g. At the same time all other medi- reflexes were within normal limits. There was marked cations were gradually withdrawn as the patient was bradykinesia (had great difficulty in getting out of reluctant to take them. Within 4 weeks of treatment the chair, as mentioned earlier), positive glabellar tap with L-dopa, there was a considerable improvement in addition to other features of parkinsonism pre- in her bradykinesia and she was able to get up from a viously mentioned. Episodes of involuntary eye low chair unaided and was able to walk fairly closure, and also the fact that he had to open the eye- steadily. The incidence of falls became much less. lids manually, were observed during examination of There was a marked improvement in her depression. the patient. Blepharospasm completely disappeared. No change Medication for the last few years was benzhexol in tremor was noticed. Palmo-mental and glabellarProtected by copyright. 4 mg t.d.s. The patient was placed on oral L-dopa reflexes were reversed. 250 mg b.d. which was gradually increased by 250 The only side effect noticed was slight drowsiness. mg every 3-4 days until a total daily dosage of 2-5 g was reached. Benzhexol was continued as before. Case 3 Within 4 weeks of treatment the patient made a con- G.R. is a 73-year-old male with a 4-year history of siderable improvement-blepharospasm completely parkinsonism. Marked facies, tremor of right hand, disappeared, rigidity much reduced and there was cogwheel rigidity of all the limbs, marked brady- slight improvement in the tremor of the hands. kinesia (was recently virtually confined to bed and Great improvement in bradykinesia was noticed and chair) and frequent uncontrollable blinking of both he was able to get out of a low chair and was able to eyes (blepharospasm) were noticed. He had stooped walk along the corridor quite well. Balance improved posture, confusion and marked depression. No his- and he had no further falls. Speech became distinct. tory of encephalitis. He had a feeling of well-being and became cheerful Neurological examination revealed moderate (depression lifted). mental impairment (scored 6/10 on mental status http://pmj.bmj.com/ No side effects from L-dopa were observed. questionnaire test). Sensations were within normal limits. Cranial nerves and deep tendon reflexes re- vealed no abnormality. Postural stability was not Case 2 tested because the patient was unable to stand with- I.W. is a 68-year-old female. She has a 10-year out assistance. history of parkinsonism and has received hospital He was commenced on L-dopa 250 mg b.d. which treatment for at least 5 years. Initially, no rigidity but was gradually increased every 3-4 days by 250 mg on September 27, 2021 by guest. fairly gross tremor of the hands was noted. She had until a daily dosage of 2-250 g was reached. Initially, been having frequent falls. Gradually the tremor of no improvement was noticed. Later, a gradual im- the hands became more marked and also the tremor provement took place and in about 6-8 weeks brady- of the jaw appeared. Masked facies, frequent in- kinesia improved considerably and he was able to voluntary closure of eyelids (blepharospasm), some get out of a chair and walk along the corridor un- cogwheel rigidity, bradykinesia (great difficulty in aided. His confusion improved and he became getting out of chair unaided), poor balance and cheerful (depression lifted). Blepharospasm was less positive glabellar tap were noted. There was also but still present. Rigidity was reduced and there was shuffling gait, anteropulsion and retropulsion and no significant change in tremor. He still had positive the body became stooped. There was excessive palmo-mental and glabellar reflexes. His balance salivation. was much improved. Her past history includes depression but no history The only side effect was increased sexual desire but of encephalitis. he did not require any treatment for this. Postgrad Med J: first published as 10.1136/pgmj.50.586.521 on 1 August 1974. Downloaded from Case reports 523 Discussion hibition of the neurones of the striatum (Klawans Blepharospasm is an unusual manifestation in and Goodwin, 1969). parkinsonism but this has been a well recognized symptom of the disease (Klawans and Erlich, 1970). Acknowledgments I wish to thank Miss Fairweather, the librarian, and Mrs In some cases, blepharospasm may be so severe as V. S. Pawson, medical shorthand-typist, for their almost to prevent useful vision and may also be help. associated with painful contractions of the muscles References of the eyelids. It is more frequent in post-encephalitic BARBEAU, A. & McDOWELL, F.H. (1970) L-Dopa and than idiopathic parkinsonism. Parkinsonism. F. A. Davis, Philadelphia. The first patient presented with difficulty in useful CALNE, D.B. (1970) Parkinsonism: Physiology, Pharma- cology and Treatment. Arnold, London. vision and pain in the eyes which was relieved within HALL, M.R.P. (1973) Drug therapy in the elderly. British a short period following commencement of treatment Medical Journal, 3, 583. with L-dopa. With regard to the other two cases, HORNYKIEWICZ, 0. (1966) Dopamine and brain function. life became more comfortable when blepharospasm Pharmacology Review, 18, 925. KLAWANS H.L. (1968) Pharmacology of Parkinsonism. A was relieved. In all these patients, there was also re- review. Diseases of the , 29, 805. markable improvement in parkinsonism, depression KLAWANS H.L. & GOODWIN J. (1969) Reversal of the and general condition (i.e. a feeling of well being). glabellar reflex in Parkinsonism by L-Dopa. Journal of L-dopa now seems to be a major therapeutic , Neurosurgery and Psychiatry, 32, 423. KLAWANS, H.L., & ERLICH, M.A., JR (1970) Observations on advance and most effective treatment of Parkinson's the mechanisms of Parkinsonian blepharospasms and its disease, particularly for the akinesia and parkin- treatment with L-Dopa. European Neurology, 3, 365. sonian blepharospasm. Although all the patients (in MATTHEWS, W.B. & MILLER, H. (1972) Diseases of the this series) were elderly, a daily maintenance dose of Nervous System. p. 233. PARKES, J.D. & MARSDEN, C.D. (1973) The treatment of Protected by copyright. about 2 g of L-dopa was tolerated and there were Parkinson's disease. British Journal of Hospital Medicine, no significant side effects. 10, 284. It was interesting to observe that in two cases the PENDERS et al. (1971) Blink reflex studies in patients with initial positive glabellar reflex was reversed following Parkinsonism before and during therapy. Journal of Neurology, Neurosurgery and Psychiatry, 34, 674. treatment. It has been suggested that the reversal is WALSH, S.B. & HOYT, W.F. (1969) Clinical Neurophthalmo- secondary to the re-establishment of dopamine in- logy. 3rd edition. Williams & Wilkins.

Postgraduate Medical Journal (August 1974) 50, 523-524.

Penile Parkinsonism

M. P. OSBORNE http://pmj.bmj.com/ M.B., B.S. St James' Hospital, Balham, London*

Summary with a persistent painful erection for 48 hr. The onset Priapism following the adminiistration of the tran- of the priapism occurred following the administra- on September 27, 2021 by guest. quillizer pericyazine (Neulactil) is reported. No other tion of a prescription for pericyazine (Neulactil) 25 aetiology was found after full investigation. The condi- mg t.d.s. The patient had taken the first tablet, tion resolved during treatment with intravenous benz- retired to bed and had sexual intercourse. He awoke tropine (Cogentin). An attempt has been made to the following morning with priapism, and continued explain the aetiology and rationalize the treatment to take the tablets for a further 24 hr. The tablets given. were prescribed for anxiety following a domestic disturbance. There was no relevant previous medical Case report history and he had otherwise enjoyed History good health. A 37-year-old Caucasian paper merchant pre- Clinical examiniation sented to the accident and emergency department A fit looking, well nourished man in considerable * Present Address: Dr M. P. Osborne, West Herts Hos- pain. Apyrexial with no lymphadenopathy, the pital, Hillfield Road, Hemel Hempstead, Herts. cardiovascular and respiratory systems were normal.