to his cardiac disease or his weak respiratory musculature. At 28 months he developed congestive heart failure that was controlled with medication. In fact, he was asymptomatic of heart failure at the time of admission for cardiac catheterization, Central. core and multicore disease have some striking similarities in their pathologic lesions' and this could suggest related pathogenetic mechanisms resulting in these two diseases. Central core disease has been associated with malignant hyperthermia syndrome during anes- thesia."" Problems with anesthesia have not previously been described in any patients with multicore disease. Our patient had a high, unexplained fever, acidosis, and tachyeardia after receiving lidocaine and ketamine, agents previously associated with malignant hyperthermia.11,19 Hyperthermia could have been precipitated by medication or the stress of cardiac catheterization.11,10 Our patient did not have muscle rigidity, elevated creatine kinase levels, or myoglobinuria, as would have been expected for malignant hypertherinia. However, nonrigid forms of the syndrome have been described." Laboratory tests cannot identify all patients with this condition. 12 Although the cause of death could have been an allergic reaction to the contrast media, 21 or from sepsis, the clinical and autopsy findings do not support these diagnoses and the cause of death is more likely related to anesthesia. We would like to acknowledge Barbara Pepper and Lou Grubbs for their technical assistance, and John Whitaker, MD, for reviewing the manu- script. References 1. Engel AG, Gomez MR, Groover RV: Multi- core disease: A recently recognized congenital myopathy with multifocal degeneration of muscle fibers. Mayo Clin Proc 1971;46:666-681. 2. Mukoyama M, Matsuoka Y, Kato H, et al: Multicore disease. Rinsho Shinkeigaku 1973; 13:221-227. 3. Tanimura R, Suzuki H, Yokota J, et al: Multicore myopathy: A case of congenital nonprogressive myopathy with 'multicore' changes of muscle fibers. Rinsho Shinkeigaku 1974; 14:613-622. 4. Currie S, Noronha M, Harriman D: 'Minicore disease,' in Bradley WG (ed): 111. International Congress on Muscle Disease (International Congress Series, No. 334). Amsterdam, Excerpta Medica, 1974, p 12. 5. Heffner R, Cohen M, Duffner P, et al: Multicore disease in twins. J Neurol Neurosurg Psychiatry 1976;39:602-606. 6. DeLumley L, Vallat JM, Catanzano G: Etude clinique et ultrastructure d'un cas myo.pathie congenitale a foyers multiples. Ann Pediatr 1976;23:333-336. 7. Taratuto AL, Sfaello ZM, Rezzonico C, et al: Multicore disease: Report of a case with lack of fibre type differentiation. Neuropediatria 1978;9:285-297. 8. Dubowitz V: Muscle disorders in childhood, in The Congenital Myopathies. Philadelphia, WB Saunders Co, 1978, vol 16: Muscle Disorders in Children, pp 73-77. 9. Ricoy JR, Cabello A, Goizueta G: Myopathy with multiple minicores: Report of two siblings. J Neurol Sci 1980;48:81-92. 10. Isaacs H, Badenhorst M: Multicore disease. S Afir Med J 1980;57:543-546. 11. Bonnette H, Roelofs R, Olson WH: Multicore disease: Report of a case with onset in middle age. Neurology 1974;24:1039-1044. 12. Brooke MH, Engle WK: The histographic analysis of human muscle biopsies with regard to fiber types: 1. Adult male and female. Neurology 1969;19:221-233. 13. Brooke MH, Engle WK: The histographic analysis of human muscle biopsies with regard to fiber types: IV. Children's biopsies. Neurology 1969;19:591-605. 14. Eng GD, Epstein BS, Engel WK, et al: Malignant hyperthermia and central core disease in a child with dislocating hips. Arch Neurol 1978;35:189-197. 15. Denborough MA, Dennett X, Anderson RMcD: Central core disease and malignant hyperpyrexia. Br Med J 1973;1:272-273. 16. Harati Y, Butler FI, Scott Cl, et al: Central core disease and malignant hyperthermia syndrome. Neurology 1978;28:405. 17. Frank JP, Harati Y, Butler IJ: Central core disease and malignant hyperthermia syndrome. Ann Neurol 1980;7:11-17. 18. Stehling LC: Anesthesia update #6. Orthop Rev 1980;9:33. 19. Roervik S, Stovner J: Ketamine induced acidosis, fever, and creatine kinase rise. Lancet 1974;2:1384. 20. Wingard DW: Malignant hyperthermia: A human stress syndrome. Lancet 1974;2:14501451. 21. Britt BA, Kalow W: Malignant hyperthermia: A statistical review. Can Anesth Soc J 1970;17:293-315. 22. Roland LP: Malignant hyperpyrexia: A reply. Muscle Nerve 1980;3:443-444. 23. Lalli AF: Contrast media reactions: Data analysis and hypothesis. Radiology 1980;134:112. Blepharospasm With Bilateral Basal Ganglia Infarction James R. Keane, MD, James A. Young, MD * Severe, involuntary, forceful closure of both eyelids, along with dystonia and rigidity, followed hypoxic encephalopathy in a young man whose computed tomographic scan showed symmetric infarcts of the corpus striaturn. Symptomatic blepharospasm can result from bilateral damage to the basal ganglia. (Arch Neurol 1985;42:1206-1208) Accepted for publication Aug 4, 1984. From the Department of Neurology, Los Angeles County-University of Southern California Medical Center, Los Angeles. Read in part before the Federation of Western Societies of Neurological Science Meeting, Napa, Calif,.Feb 25, 1984. Reprint requests to i2OO N State St, Los Angeles, CA 90033 (Dr Keane). 1206 blepharospasm 1.2 is consid- (CT) scanning or at autopsy, (4) their Essential of ered to be a focal to be dystonia organic origin by most neurologiStS.2,1 Some experienced students of this condition, however, maintain a belief in a predominantly psychogenic cause. Even staunch members of the organic camp acknowledge that, on occasion, blepharospasm can be mimicked by psychogenic blinking.' Features of blepharospasm and other proposed focal dystonias that might suggest a psychiatric cause include the following: (1) the movements can be duplicated voluntarily, (2) they follow an unpredictable course with worsening under stress or observation, (3) they are not associated with structural lesions on computed tomographic 4 onset may appear precipitated by an emotional crisis, and (5) the symptoms often are ameliorated by certain "trick" maneuvers that the patient has discovered. The case for an organic cause of a focal dystonia, such as essential blepharospasm, is based chiefly on the occasional appearance of identical symptoms with idiopathic parkinsoniSM,6 postencephalitic parkinsonism,',' and other basal ganglia diseases,9 as well as their association with antipsychotic drug therapy and as a side effect of levodopa therapy. Spontaneous blepharospasm following focal central nervous system lesions is decidedly rare, but a series of six such Arch Neurol-Vol 42, Dec 1985 Downloaded From: http://archneur.jamanetwork.com/ by a CAMBRIDGE UNIVERSITY LIBRARY User on 06/20/2015 Blepharospasm-Keane & Young phenomenon, causing transient functional blindness (Fig 3). In addition, relaxation of his eyelids has revealed the presence of an intermittent bilateral horizontal ocular tremor coordinated with contraction of his orbicularis muscles. Despite these problems, the patient has been satisfied with the results of surgery and is now taking levodopa (Sinemet) with some slight improvement of his parkinsonian symptoms. .......... COMMENT _i Fig 1. -Patient opens blepharospastic eyelids with dystonic fingers. Fig 2-Computed tomographic scan shows symmetric low-density lesions involving the caudate nucleus, putamen, and globus pallidus- patients has been reported recently in association with rostral brain-stem damage.10 The following patient, who developed severe blepharospasm in association with bilateral basal ganglia damage, lends further support to an extrapyramidal cause of essential blepharospasm. REPORT OF A CASE A 31-year-old man arrived at a local hospital apneic and pulseless following an intravenous self-injection of rat poison, containing warfarin sodium, taken on a dare. Following successful resuscitation, he remained comatose with minimally reacting pupils and a temperature of 41 'C. His CT scan was normal and an electroencephalogram showed diffuse slowing. After three days, he began to respond purposefully. When discharged six weeks after admission, he was weak and required assistance to eat or dress. His strength and coordination slowly Arch Neurol-Vol 42; Dec 1985 Following severe cerebral hypoxia, patient experienced the delayed onset of severe, continual blepharospasm that sharply reduced his useful vision. Additional basal ganglia signs included parkinsonian postural defects and rigidity, as well as severe dystonic posturing of the hands. Symmetric basal ganglia infarcts similar to our patient's have been reported with hypoxic encephalopathy principally after carbon monoxide poisoning," but also following neardrowning12 and strangulation." Selective basal ganglia damage following ischemic-hypoxic insult has been confirmed by neuropathologic examination." Occasional parkinsonian symptoms associated with hypoxic encephalopathy provide further clinical evidence of sensitivity of the deep gray matter to ischemia.11 Essential blepharospasm and blepharospasm associated with orofacial dystonia (Meige syndrome)," like torsion dystonia, are not associated with structural central nervous system pathology. Postencephalitic parkinsonism and other basal ganglia diseases occasionally associated with blepharospasmll generally do not show sufficiently discrete pathologic lesions for clinicopathologic correlation. However, three of Jankovic and Patel's10 six patients with symptomatic blepharospasm showed CT evidence of thalamic/upper midbrain infarcts and all displayed symptoms pointing to this general anatomic area. Their patients developed blepharospasm after delays ranging from two days to three years following infaretion (four patients) and involvement with multiple sclerosis (two patients). The present treatment of blepharospasm is empirical and generally unsatisfactory. Many medicines, seemingly without regard to a simple pharmacologic explanation for blepharospasm, provide some relief, for some time, for some patients. No drug provides predictable long-lasting relief. Surgical therapy can alleviate orbicularis spasm either through our Fig 3.-Blepharospasm (top) is relieved following serial orbicularis denervations (bottom) but upward eye deviation associated with Bell's phenomenon persists (bottom). improved, but six months after discharge, he developed progressive basal ganglia symptoms including blepharospasm. He was first seen in neurologic consultation at our hospital 16 months after cardiac arrest because forceful bilateral eyelid squeezing had rendered him functionally blind, and he was unable to continue his program of physical therapy. Examination showed an alert individual able to comprehend and follow complex commands and to perform simple memory and arithmetical tests. His voice was slow, monotonous, and poorly articulated. Moderate bradykinesia and severe truncal and extremity rigidity were present, and he walked stooped over with small steps and a tendency to festinate. Both hands were distorted by severe dystonic posturing (Fig 1). No definite weakness, sensory loss, or cerebellar imbalance could be demon- strated. His eyelids were in a state of almost constant closure. At times he *as able to extend his neck and peer out through a small aperture on the left, but usually he had to manually elevate the eyelids to see at all (Fig 1). Any attempts by others to manipulate his eyelids increased the intensity of blepharospasm; when the contractions were severe, his lower facial muscles participated to a slight extent. The mouth, tongue, and neck were not involved with involuntary movements. The CT scan now showed symmetric low-density infarctions of the corpus striaturn superimposed on mild diffuse cerebral atrophy (Fig 2). Nearly a year of medical therapy with increasing doses of diazepam (to 30 mg/ day), trihexyphenidyl hydrochloride (to 18 mg/day), and clonazepam (to 3 mg/day) provided only slight and inconstant relief. He then underwent serial surgical denervation of the facial nerve branches to the orbicularis oculi muscles with successful relief of blepharospasm. However, six months following surgery, he continued to experience a central epiphenomenon of blepharospasm. During intense "spasms" revealed by fasciculations of his few innervated orbicularis muscle fibers, his eyes rolled up with Bell's selective facial nerve denervation or Blepharospasm-Keane & Young Downloaded From: http://archneur.jamanetwork.com/ by a CAMBRIDGE UNIVERSITY LIBRARY User on 06/20/2015 1207 by directly cutting the muscle. Use of botulinum toxin to weaken the orbicularis muscle is a recently described alternative to surgical myectomy. Our patient failed to respond to medical therapy and underwent bilateral upper facial denervation. Although he, himself, is satisfied with the surgical outcome, "squeezeless" episodes with Bell's phenomenon persist. This patient, with unusually severe extrapyramidal deficits following cardiac arrest, adds further support to a basal ganglia origin of essential 16 blepharospasm. References 1. Henderson JW: Essential blepharospasm. Trans Am Ophthalmol Soc 1956;54:453-520. 2. Jankovic J, Havins WE, Wilkins RB: Blink- ing and blepharospasm: Mechanism, diagnosis, and management. JAMA 1982;249:3160-3164. 3. Marsden CD: The problem of adult-onset idiopathic torsion dystonia and other isolated dyskinesias in adult life (including blepharospasm, oromandibular dystonia, dystonic writer's cramp, and torticollis, or axial dystonia), in Eldridge R, Fahn S (eds): Advances in Neurology. New York, Raven Press, 1976, vol 14, pp 259276. 4. Trobe JD: Blepharospasm. Audio-Digest Ophthalmol 1984;22.5. 5. Lesser RP, Fahn S: Dystonia: A disorder often misdiagnosed as a conversion reaction. Am J Psychiatry 1978;135:349-352. 6. Klawans HL, Erlich MA: Observations on the mechanism of parkinsonian blepharospasm. and its treatment with L-dopa. Eur Neurol 1970;3:365-372. 7. Metz LN, Magee KR: Postencephalitic blepharospasm. Arch Neurol 1960;60:692-697. 8. Alpers BJ, Patten CA: Paroxysmal spasm of the eyelids as a postencephalitic manifestation. Arch Neurol Psychiatry 1927;18:427-433. 9. Zeman W, Kaeblins R, Pasamanick B: Idiopathic dystonia musculorurn deformans: IL The formes frustes. Neurology 1960;10:1068-1074. 10. Jankovic J, Patel SC: Blepharospasm associated with brainstern lesions. Neurology 1983; 33:1237-1240. 11. Choi IS: Delayed neurologic sequelae in carbon monoxide intoxication. Arch Neurol 1983; 40:433-435. 12. Murray RR, Kapila A, Blanco E, et al: Cerebral computed tomography in drowning victims. AJNR 1984;5:177-179. 13. Dooling EC, Richardson EP: Delayed encephalopathy after strangling. Arch Neurol 1976;33:196-199. 14. Ringel SP, Klawans HL: Carbon monoxideinduced parkinsonism. J Neurol Sci 1972;16:245251. 15. Jankovic J, Ford J: Blepharospasm and orofacial-cervical dystonia: Clinical and pharmacological findings in 100 patients. Ann Neurol 1983;13:402-411. 16. O'Connor PS: An oculinum report, editorial. J Clin Neuro Ophthalmol 1983;3:227-228. Paraneoplastic Cerebellar Disease Remission With Excision of the Primary Tumor John H. Kearsley, MB; Peter Johnson, MB; G. Michael Halmagyi, MB e We describe two patients with paraneoplastic cerebellar syndromes who gained clinically useful neurologic remissions following radical excision of the primary cancer. In both patients the syndrome was characterized by the rapid onset of gait ataxia, nausea, postural vertigo, central positional nystagmus, and saccadic oscillations. These observations encourage radical treatment of the primary cancer in patients with advanced malignant neoplasms who are disabled by cerebellar dysfunction, and lend support to a current hypothesis that paraneoplastic cerebellar degeneration is due to anticerebellar Purkinje cell antibodies elaborated by the primary cancer. (Arch Neurol 1985;42:1208-1210) progressive cerebellar syndrome, A due in some cases to cerebellar cortical degeneration, has been well described in cancer patients, commonly in those with lung cancer, ovarian Accepted for publication July 3, 1984. From the Department of Neurology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales. Reprint requests to Department of Neurology, Royal. Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales 2050, Australia (Dr Halmagyi). 1208 Arch Neurol-Vol 42, Dec 1985 cancer, or neuroblastoma.1-4 In most patients the neurologic deficit accumulates over several months and indicates diffuse cerebellar dysfunction. 1,4 In others, however, the onset is abrupt,','-' and gait ataxia, nystagmus, myoclonic jerks, and saccadic oscillations are prominent features.","' Most authorities accept that the cerebellar syndrome in such cases is somehow;caused by the remote caneer,1-1-4,11 and mechanisms suggested include the following- (1) cerebellotoxic substances, in particular antiPurkinje cell antibodies elaborated by the tumor,12-11 (2) opportunistic viral infections, 1.16 and (3) nutritional deficiencies perhaps due to the metabolic activity12_17. of the malignant neo- plasm. Remission of the cerebellar syndrome with treatment of malignant neoplasms has been rarely reported.5-7,17,11 Such cases are important, however, as they support the hypothesi s that primary cancers can cause cerebellar dysfunction by elaborating cerebellotoxic substances such as anti-Purkinje antibodies. In support of this hypothesis, we describe two patients with advanced malignant neoplasms who had, following extirpation of the primary cancer, gained temporary near-complete remissions from disabling cerebellar syndromes. Report of Cases CASE L-A previously well 63-year-old suddenly developed intense nausea, vertigo, and inability to stand and was man brought to a hospital. On examination, he appeared acutely sick and lay immobile on his right side. In the sitting posture, he had first-degree nystagmus to the right and to the left, and visual fixation was interrupted by frequent bursts of ocular flutter. Smooth pursuit and vestibulo-ocular reflex suppression were absent in the horizontal and vertical planes. Saccadic velocities appeared clinically normal, and there was no oculornotor paresis. Rapid supine positioning with the right ear down elicited, after a latent period of about five seconds, a ten- to 15-second burst of counterclockwise nystagmus with intense vertigo. Caloric tests showed symmetrical responses, unsuppressed by fixation. There was a moderately severe high-tone sensorineural hearing loss on the right. There was no weakness or incoordination of the limbs, but a profound inability to stand unaided, with a tendency to fall backward. Tendon reflexes were normal and symmetrical, and the plantar responses were flexor. Sensation was normal. In the anterior compartment of the left Cerebellar Disease-Kearsley et al Downloaded From: http://archneur.jamanetwork.com/ by a CAMBRIDGE UNIVERSITY LIBRARY User on 06/20/2015