J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.50.2.237 on 1 February 1987. Downloaded from

Letters 237 troencephalogram (EEG) showed a diffuse with myelofibrosis and symptomatic ana- frontal enhancing nodule abutting the ring. monorhythmical 9-12Hz activity of 50pV emia.2 3 We report the second such case in He was started on dexamethasone with amplitude, with no reactivity to painful stim- which pancytopenia resulting from marrow significant improvement of his intellectual ulation. Multi-drug screening tests estab- invasion was the primary clinical function and to a lesser degree his right sided lished intoxication with a benzodiazepine presentation. In addition, white matter weakness. Over the next 2 months, the later identified as flunitrazepam. degeneration due to the effects of radio- patient's haematological function worsened, On the second day the patient gradually therapy and possible chemotherapy caused a with slowly declining platelets and hae- regained consciousness. A repeat EEG at major diagnostic dilemma. The importance moglobin levels. Intermittent transfusions that time was normal. After recovery he of glial fibrillary acid protein staining to were required to maintain a haematocrit admitted an attempt at suicide taking 25 tab- confirm the diagnosis of metastatic glioma above 20. Alkaline phosphatase continued lets each of 2 mg of flunitrazepam. while the patient is alive is demonstrated. to be elevated. Chest radiograph was inter- This case presented two features which A 52 year old business executive was well preted as showing diffuse bony metastases. have not previously been reported in until 1972 when he suffered a generalised sei- activity became more difficult to benzodiazepine-intoxication. Firstly, the zure. A complete evaluation was negative control so that carbamazepine was substi- asymmetrical neurological signs suggested aside from an EEG which revealed left tuted for primidone. Dexamethasone was this patient had a structural brainstem lesion frontal slowing. He remained neurologically increased to 6 mg qid because the which can not always reliably be excluded by intact aside from occasional right focal and right sided weakness became worse. A CT scan. This emphasises the necessity of motor until 1980 when he developed repeat CT scan in October 1982 revealed no multi-drug screening tests in every patient mild aphasia. A CT scan revealed a contrast significant interval change however. with " of unknown origin" even in the enhancing lesion in the left parietal region. Several attempted bone marrow aspirates presence of lateralizing signs. Secondly, an Tumour removed by subtotal resection in and biopsies failed to produce adequate alpha coma is relatively rare and has been April 1980 was considered to be a Grade III specimens for diagnosis. A biopsy specimen associated with hypoxic of astrocytoma. The patient continued to in November 1982 showed a monomorphic primary brainstem lesions.1 Occasionally worsen and in June 1980, an extensive proliferation of a malignant cell line of however this type of EEG pattern results was resection performed. Between July 18, undetermined type. He continued to require guest. Protected by copyright. from an overdose of drugs such as glu- 1980 and August 21, 1980 he received 5000 transfusion of both blood and platelets. His tethimide, barbiturates and amytriptyline.2 rads whole brain radiotherapy in 25 neurological status continued to deteriorate, Unlike the patients with hypoxic encepha- fractions. A boost of 1000 rads was deliv- although repeat CT scan again did not lopathy, a drug-induced alpha pattern coma ered in five fractions to the left frontal reveal any significant change. The patient has a good prognosis.3 This case demon- region. Following this the patient received died in December 1982 from complications strates that flunitrazepam also should be six three day courses of intravenous BCNU of pancytopenia and adult respiratory dis- included in the list of drugs that can cause given 6 weeks apart from October 1980 to tress syndrome. alpha pattern coma. June 1981 totalling 1600 mg/m. Pro- The general necropsy revealed a non- DIRK DELEU carbazine was given daily from July 1981 to malignant pleural effusion, early pneumonia JAAK DE KEYSER November 1981 and again from January and an old . The Department of Neurology, 1982 to February 1982. He was admitted to spleen revealed small areas of extra- University Hospital A.Z.- V.U.B. the Roger Williams General Hospital on medullary haematopoiesis. The vertebrae Laarbeeklaan, 101 July 2, 1982 because of increasing right- were infiltrated by a white tissue which on 1090 Brussels, Belgium sided weakness and lethargy. Physical exam- microscopic examination was found to be ination was remarkable only for a moderate composed of small undifferentiated tumour References aphasia and a mild right hemiparesis. Labo- cells identical to those noted in the surgical I Chokroverty S. Alpha-like rhythms in electro- ratory values included: WBC, Hgb. 118% brain specimen of 4/22/80. These cells were encephalograms in coma after . mg HCT 32 9%, MCV 96, Platelets 197,000. positively stained with immunoperoxidase Neurology 1975;25:655-63. The blood smear appeared normal. for glial fibrillary acid protein. In the brain, 2 Carroll WM, Mastaglia FL. Alpha and beta Fe/TIBC = 44/l65. SMA6, VDRL, PT, a cavitative necrotic lesion of about 4 cm in coma drug intoxication uncomplicated by APTT and SMA12 were normal aside from: surrounded by a brownish gliotic zone was cerebral . Electroencephalogr Clin http://jnnp.bmj.com/ Neurophysiol 1979;46:95- 105. lactate dehydrogenase 418 U/I (normal found in the left fronto-parietal region. 3 Kuriowa Y, Furakawa T, Kuzumoto I. Recov- 80-210), alkaline phosphatase 438 U/I There was a mild yellowish discoloration of ery from drug-induced alpha coma. Neuro- (50-260), serum glutamic-oxaloacetic trans- the adjacent white matter of the centrum logy 1981;31:1359-61. aminase 31 U/I (5-30), 385 mg% semiovale. The left lateral ventricule was (160-300). Stool was negative for occult slightly dilated at the frontal end due to glio- blood. Chest radiographs revealed an sis of the adjacent white matter. The cere- abnormal liner density in the right lung base bellum, pons and medulla showed no Distant metastases from a malignant glioma: thought to be either scarring or a sub- significant change. External to the necrotic associated with treat- area of unusual complications segmental atelectasis. The right sixth area was a zone of intense gliosis in which on September 29, 2021 by ment of a glioblastoma: distant metastases rib demonstrated a posterolateral fracture thick-walled blood vessels were seen. and focal white matter degeneration and the bones were osteopenic. Contrast Spreading from the edge of the cavity was an enhanced cerebral CT scan revealed bilat- area of graded loss of myelinated nerve Sir: Gliomatous metastases have been found eral ventricular enlargement, left greater fibres. ranging from total destruction to a in the liver, bone, lung, pleural cavity, than right, with a semicircular ring enhanc- subtle spongiosis of the white matter. There pericardium and lymph nodes.' Only rarely ing lesion adjacent to the skull in the left was, however, widespread blood vessel do patients develop bone marrow invasion superior anterior region and a small left thickening even in areas where there was J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.50.2.237 on 1 February 1987. Downloaded from

238 Letters only a mild degree of nerve fibre loss. The prolonged survival becomes more common Optico-acoustic atrophy in distal spinal corpus callosum showed severe loss of nerve with this tumour, clinicians may see an muscular atrophy fibres, increased numbers of glial cells, reac- increasing number of similar complications. tive astrocytes and focal necrosis. The cau- Staining for glial fibrillary acidic protein Sir: The triad of hereditary motor and sen- date nucleus and internal capsule on the left may preclude a lengthy and costly search for sory neuropathy, optic atrophy and deafness side were normal. Only mild neuronal loss a second primary malignancy. was first reported in a kindred of two broth- was seen in the left globus pallidus. The cere- ers and their nephew by Rosenburg and bellum and the whole right hemisphere were Chutorian in 1967.1 A similar clinical syn- normal. Scattered giant axonal spheroids We thank John CM Brust, MD and Robert drome in a brother and sister was described were present in the posterior portion of the D Rafal, MD for suggestions and Miss in 1970.2 But for the sensory manifestations, rostral medulla. No evidence of glioma was Corrine Hopp for manuscript preparation. the clinical features of hereditary motor and found. The abnormalities described were sensory neuropathy might be confused with diagnostic of a widespread leuko- the distal form of . encephalopathy due to radiation and/or JOSEPH H FRIEDMAN,*t We report a case of distal spinal muscular chemotherapy. H MEI LIU,t§ atrophy associated with optico-acoustic ELLEN SPREMULLI,: and believe that this association has Most extraneural metastases from glio- PAUL CALABRESI,*t atrophy mas occur after craniotomy although at Roger Williams General Hospital,* not been previously described. least eight cases' have been reported, in the Divisions of Neurology and Oncology, The patient presented at the age of 10 absence of surgery. The diagnosis of system- Department of Medicine, years with visual impairment. Three years ically metastatic central 825 Chalkstone Avenue, later she became deaf and was shown to have tumours is not easy to make and is probably Providence, RI 02908 severe bilateral sensori-neural deafness 12 not often considered. Weiss4 established years later. At this time she also complained four criteria: first, the presence of a single Brown University,t ofclumsiness of her hands and was found to tumour which is histologically characteristic Providence, RI 02912, have distal muscle wasting and weakness in of a primary glioma; second, a clinical his- Anniston Medical Clinic Anniston, both upper limbs. There were no sensory tory indicating that initial symptoms were Alabama,: signs and the deep tendon reflexes wereguest. Protected by copyright. due to this tumour; third, a complete nec- Miriam Hospital, retained. ropsy excluding the possibility of any other Department of Pathology,§ Fifty-one years after initial presentation, primary site; and fourth the identical mor- Providence, RI 02906, USA she was unable to hear and understand phology of the CNS tumour and the distant speech. Visual acuity (aided) was 6/60, N18 metastases with due allowance for bilaterally. The symptoms and signs in the differences in degree of anaplasia. The use of upper limbs remained unchanged. There was glial fibrillary acidic protein, a cytoplasmic no family history of neuro-muscular disease, marker for identifying glial cells,5 provides a blindness or deafness and she had had no more definitive histological characterisation children. of tumours of neural origin and allows for References Examination revealed bilateral optic atro- the diagnosis of metastatic glioma in the phy with no pigmentary retinopathy. There 1 Pasquier B, Pasquier D, N'Golet A, et al. absence of the classical criteria.6 Extraneural Metastases of Astrocytomas was marked wasting and weakness of the The present case is unique in that three and Glioblastomas. Clinicopathological small muscles of the hands and forearms rare events in the treatment of a glio- Study of two Cases and Review of the with preserved reflexes. There were no sen- blastoma occurred in concert, namely sys- Literature. Cancer 1980;45:112-28. sory signs and no thickened peripheral temic metastasis, cure of the glioma at the 2 Dietz R, Burger L, Merkel K, el al. Malignant nerves. primary site and treatment induced leuko- Gliomas-Glioblastomas and Astrogliomas Glucose tolerance test, serum thyroxine encephalopathy. Death was from compli- Grades 111-TV with Extracranial Metastases. and were normal. No acan- to bone marrow Report of Two Cases. Acta Neurochir were seen in the peripheral blood. cations secondary (Wein) 1981;57:99-105. thocytes infiltration by glioma cells. The patient 3 Rubenstein of Extracranial Cervical spine radiographs showed mild cer-

LJ. Development http://jnnp.bmj.com/ developed progressive neurological dys- Metastases from a Malignant Astrocytoma vical spondylosis. CSF protein and gamma function from white matter degeneration in the Absence of Previous Craniotomy. globulin levels were normal. Nerve conduc- following radiation and chemotherapy while Case Report. J Neurosurg 1967;26:542-7. tion studies showed normal motor and sen- the primary tumour appeared to have been 4 Weiss L. A Metastasizing Ependymoma of the sory conduction velocities in upper and eradicated. The major problem during the Cauda Equina. Cancer 1955;8:161-71. lower limbs. Sensory action potentials were patient's last several months related to his 5 Deck JHN, Eng LF, Bigbee J, et al. The Role of normal amplitude (right ulnar lOjV, of Glial Fibrillary Acidic Protein in the pancytopenia. The diagnosis of metastatic Diagnosis of Central Nervous System right sural 12,pV). Electromyography glioma was not considered until necropsy. Tumours. Acta Neuropathol 1978;42:183-90. showed evidence of chronic partial Marrow suppression was initially thought 6 Young DF. Diffuse denervation with polyphasic potentials and Yung WKA, Tepper SJ, on September 29, 2021 by due to chemotherapy. Terminally, when a Bone Marrow Metastasis by Glioblastoma: giant units to 12mV in proximal and distal bone marrow biopsy produced malignant Premortem Diagnosis by Peroxidase- muscles in upper and lower limbs. Spontane- cells, a second malignancy was thought to Antiperoxidase Staining for Glial Fibrillary ous activity was sparse. Muscle biopsy (left have developed. This case suggests that Acid Protein. Ann Neurol 1983;14:581-5. deltoid) showed fibre-type grouping com- combined radiation and chemotherapy were patible with the electromyographic findings. effective in treating the glioma but were the Visual evoked potentials (chequerboard pat- cause of white matter degeneration. As Accepted 17 April 1986 tern reversal) were delayed bilaterally. The