- Email: [email protected]
Sensorimotor polyneuropathy with 5-aminosalicylic acid: a case report
386 Ono et al.
Fig. 3 Axial contrast-enhanced CT scan showing the large left cerebellopontine angle acoustic schwannoma. The internal auditory meatus is widened.
inadequate and even chaotic behaviour. We analyzed the various benign tumours reported to be associated with pathological laughter. Dumbbell shaped large trigeminal neurinoma is more common amongst these tumours.2;3 The combination of pressure over the brainstem and the medial temporal brain structures could be the probable mechanism of pathological laughter in these tumours. As tumours located entirely in the posterior fossa22–28 have been reported to result in pathological laughter, pressure or hump of the brainstem appears more crucial than pressure over the temporal brain. Considering that pathological laughter as a presenting symptom occurs only extremely rarely, a complex combination of factors must be essential for a tumour to cause pathological laughter. Both the acoustic schwannomas presented had a more medial location. It appears that compression of the brainstem at or just below the level of the tentorium producing a typical hump of the brainstem could be responsible for production of the symptom of pathological laughter. In majority of reported cases, the pathological laughter was completely abolished after the tumour resection. In the presented cases and those reported earlier,2;3;27 there was a well-defined dissection plane between the tumour and the brainstem. This suggests that it is only pressure or distortion of the neural structures rather than a permanent damage or a vascular insufficiency that initiated the chain of events. REFERENCES 1. Achari AN, Colover J. Posterior fossa tumours with pathological laughter. JAMA 1976; 235: 1469–1471. 2. Bhatjiwale MG, Goel A, Desai KI. Pathological laughter as a presenting symptom of trigeminal neurinoma. Case report. Neurol Med Chir (Tokyo) 1996; 36: 644–646. 3. Bhatjiwale MG, Nadkarni TD, Desai KI, Goel A. Pathological laughter as a presenting symptom of massive trigeminal neuromas: report of four cases. Neurosurgery 2000; 47: 469–471. 4. Matsuoka S, Aragaki Y, Numaguchi K, Hinokuma K. A case of angioblastic meningioma with pathological laughter – with special reference to laughter in brain tumour. Neurol Med Chir (Tokyo) 1977; 17: 195–201 [Japanese, with English abstract].
Journal of Clinical Neuroscience (2003) 10(3)
5. Matsuoka S, Yokota A, Yasukouchi H et al. Clival chordoma associated with pathological laughter. J Neurosurg 1993; 79: 428–433. 6. Monteil P, Cohadon F. Pathological laughing as a symptom of a tentorial edge tumour. J Neurol Neurosurg Psychiatry 1996; 60: 370. 7. Nadkarni TD, Goel A. Trochlear nerve neurinoma presenting as a pathological laughter. Br J Neurosurg 1999; 13: 212–213. 8. Cairns H. Mental disorders with tumours of the pons. Folia Psychiatr Neurol Jpn 1950; 53: 193–203. 9. Adams RD, Victor M, Ropper AH. The limbic lobes and the neurology of emotion. In: Adams RD, Victor M (eds) Principles of Neurology. sixth ed. McGraw Hill, New York 1997; 508–521. 10. Ironside R. Disorders of laughter due to brain lesions. Brain 1956; 79: 589–609. 11. Asfora WT, DeSalles AA, Abe M, Kjellberg RN. Is the syndrome of pathological laughing and crying a manifestation of pseudobulbar palsy? J Neurol Neurosurg Psychiatry 1989; 52: 523–525. 12. Couderq C, Drouineau J, Rosier MP, Alvarez A, Gil R, Neau JP. Pathological laughter after the brainstem infarction. Rev Neurol (Paris) 2000; 156: 281–284 [French, with English abstract]. 13. Kubik CS, Adams RD. Occlusion of the basilar artery: a clinical and pathological study. Brain 1946; 69: 73–121. 14. Black DW. Pathological laughter. A review of the literature. J Nerv Ment Dis 1982; 170: 67–71. 15. Tei H, Sakamoto Y. Pontine infarction due to basilar artery stenosis presenting as pathological laughter. Neuroradiology 1997; 39: 190–191. 16. Garg RK, Misra S, Verma R. Pathological laughter as heralding manifestation of left middle cerebral artery territory infarct. Case report and review of literature. Neurol India 2000; 48: 388–390. 17. Davison C, Kelman H. Pathological laughing and crying. Arch Neurol Psychiatry 1929; 42: 595–643. 18. Stern WE, Brown WJ. Pathological laughter. J Neurosurg 1957; 14: 129–139. 19. Gopinath SP. Pathological laughter. J Neurosurg 1994; 80: 596–597. 20. Gottwald W. Paroxyms of pathological laughter and crying. Med Welt 1982; 33: 622–626 [German]. 21. Pecker J, Delaitre R, Guy G, Faivre J. Pathological laughter in brain stem diseases. Rev Otoneuroophtalmol 1970; 42: 236–238. 22. Cantu RC. Importance of pathological laughing and/or crying as a sign of occurrence or recurrence of a tumour lying beneath the brainstem. J Nerv Ment Dis 1966; 143: 508–512. 23. Cantu RC, Drew JH. Pathological laughing and crying associated with a tumour ventral to the pons. Case report. J Neurosurg 1966; 24: 1024–1026. 24. Lal AP, Chandy MJ. Pathological laughter and brainstem glioma. J Neurol Neurosurg Psychiatry 1992; 55: 628–629. 25. Osumi Y, Yamadori A, Tamaki N. Case of ventrally situated brainstem meningioma associated with forced laughter. Rinsho Shinkeigaku 1976; 16: 715–720 [Japanese, with English abstract]. 26. Shafqat S, Elkund MSV, Chiocca EA, Takeoka M, Koroshetz WJ. Petroclival meningioma presenting with pathological laughter. Neurology 1998; 50: 1918–1919. 27. Muzumdar D, Agrahar P, Desai K, Goel A. Pathological laughter as a presenting symptom of petroclival meningioma – case report. Neurol Med Chir (Tokyo) 2001; 41: 505–507. 28. Stevenson GC, Stoney RJ, Perkins RK, Adams JF. A transcervical transclival approach to the ventral surface of the brainstem for removal of a clivus chordoma. J Neurosurg 1966; 24: 544–551. 29. Parvizi J, Anderson SW, Martin CO, Damasio H, Damasio AR. Pathological laughter and crying: a link to the cerebellum. Brain 2001; 124: 1708–1719.
Sensorimotor polyneuropathy with 5-aminosalicylic acid: a case report Kenjiro Ono1 MD, Kazuo Iwasa2 Masaharu Takamori3 MD
MD,
Hiroe Shirasaki1
MD,
1 Department of Neurology and Neurobiology of Aging, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan, 2Department of Neurology, National Kanazawa Wakamatsu Hospital, Se-103-1 Wakamatsu-machi, Kanazawa, Ishikawa 920-1183, Japan, 3 Neurological Center, Kanazawa-Nishi Hospital, Kou-77 Kanazawa-kita-machi, Kanazawa, Ishikawa 920-0055, Japan
ª 2003 Elsevier Science Ltd. All rights reserved.
Sensorimotor polyneuropathy with 5-aminosalicylic acid
Summary A 69-year-old man with ulcerative colitis (UC) developed sensorimotor polyneuropathy. First, he received salazosulphapyridine (SASP) as treatment for the UC. The symptoms of UC disappeared immediately, but he developed skin eruptions and dysesthesia in his lower limbs. When SASP was changed to 5aminosalicyclic acid (5-ASA), his skin eruptions were resolved, however, he developed weakness and atrophy in his right arm as well as progressive worsening of the dysesthesia in his legs and gait disturbance. Deep tendon reflexes (DTR) were absent in all extremities. After 5-ASA was discontinued, the polyneuropathy symptoms recovered gradually. This clinical course suggests that the sensorimotor polyneuropathy may have been caused by 5-ASA. ª 2003 Elsevier Science Ltd. All rights reserved. Journal of Clinical Neuroscience (2003) 10(3), 386–389 ª 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0967-5868(03)00066-3
Keywords: sensorimotor polyneuropathy, ulcerative colitis, 5-aminosalicylic acid (5-ASA) Received 22 February 2002 Accepted 16 March 2002 Correspondence to: K. Ono MD, Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Tel.: +81-76-265-2290; Fax: +81-76-234-4253; E-mail: [email protected]
INTRODUCTION Ulcerative colitis (UC) is a nonspecific inflammatory disease of unknown aetiology, which usually affects the colonic mucosa and often produces erosions and ulcers. The treatments for UC are the administration of salazosulphapyridine (SASP) or 5-aminosalicylic acid (5-ASA) and steroid. SASP is known to be decomposed by enteric bacteria into sulphapyridine (SP) and 5ASA.1 Neuropathy that is associated with SASP has been documented,24 but neuropathy caused by 5-ASA has been rarely reported.5;6 Neurological disorders associated with UC, such as neuropathy, myelopathy or myasthenia gravis have been reported,7 however, the association of neuropathy with UC is
387
uncommon and the pathogenesis is unknown.810 We present a patient who developed sensorimotor polyneuropathy during treatment for UC, and this polyneuropathy recovered after the medication was discontinued.
CASE REPORT A 69 year old shopkeeper presented with abdominal pain and diarrhoea in May 1997. He was diagnosed as UC by colonoscopy and colonic biopsy. There was no family history of UC. Medication consisting of oral SASP 3 g/day was started in June 1997. His abdominal pain and diarrhoea improved immediately. One month after the start of SASP, he had skin eruptions and mild dysesthesia on his lower limbs (Fig. 1). A dermatologist confirmed the diagnosis of drug toxico-dermatitis. SASP was changed to 5-ASA 750 mg/day in July 1997. The skin eruptions disappeared after the drug was changed, but the dysesthesia of his lower limbs progressed and, in September 1997, he noticed muscle weakness in his right arm and leg. Five months after the initial onset of dysesthesia on his lower limbs, he noticed that he had muscle atrophy of his right arm and gait disturbance. When he was admitted to our hospital in March 1998, we did not recognise any abnormalities of his skin or abdomen by physical examination. On neurological examination, he had normal cranial nerve function and normal strength in the proximal muscles of the extremities. But his muscles were hypotonic, and his right arm and thenar muscle were atrophic. Manual muscle testing (MMT) revealed: distal right arm, 3/5; right hand, 3/5; left hand, 4þ =5; right peroneal muscle, 3/5 and bilateral toe-flexion, 3/5. Deep tendon reflexes (DTR) were absent bilaterally, and responses to plantar stimulus were flexion. Cerebellar examination was normal, dysesthesia was found in both feet but primarily on the right side; also, a decrease in distal vibration sensation was recognised in both legs. Romberg sign was negative. Gait was steppage and walking on heels was difficult. Laboratory testing showed normal blood data. Serum vitamin B1 , vitamin B12 and folic acid levels were normal. He had a normal glucose tolerance. He did not have serum autoantibodies against ganglioside, Hu, DNA or nuclear cells. N-transferase 2 phenotype was an intermediate acetylator of a normal activity type. Cerebrospinal fluid findings were normal. We could not find any malignancy. Nerve
Fig. 1 Clinical course of the patient of sensorimotor polyneuropathy with 5-ASA. After withdrawal of 5-ASA, this neuropathy recovered gradually. SASP, salazosulphapyridine; 5-ASA, 5-aminosalicylic acid.
ª 2003 Elsevier Science Ltd. All rights reserved.
Journal of Clinical Neuroscience (2003) 10(3)
388 Ono et al.
Table 1
Motor and sensory nerve conduction studies
Tested nerve
Motor nerves R median Wrist–elbow Elbow–axilla R ulnar Wrist–elbow Elbow–axilla R peroneal R tib. pos. Sensory nerves R median R ulnar R sural
12th March 1998
18th May 1998
dAMP (lV)
CV (m/s)
dAMP (lV)
9.8 (wrist) 9.8 (elbow)
52.2 52.9a
11.1 8.2
59.1 66.4
6.6 (wrist) 5.5 (elbow) 5.0 11.5
54.1 45.1a 39.2a 38.5a
6.5 5.5 5.9 9.6
59.1 59.2 45.9 46.1
10.0 (wrist) 7.1 (wrist) Not detected
42.2 35.4
9.6 9.0 Not detected
CV (m/s)
42.8 41.0
dAMP, distal amplitude of CMAPs or SNAPs; CMAPs, compound muscle action potentials; SNAPs, sensory nerve action potentials; CV, conduction velocity; R, right; tib. pos., posterior tibial nerve. a < smaller than normal range.
conduction studies showed mildly decreased motor conduction velocities (MCV) in the right median, ulnar, peroneal and posterior tibial nerves. Sural sensory nerve responses were unrecordable bilaterally (Table 1). F-Wave frequencies and latencies in the right median, ulnar, peroneal and posterior tibial nerves were within normal range. Needle EMG demonstrated an increased duration and amplitude, and the appearance of polyphasic motor unit and giant spike in right triceps, brachioradialis, extensor carpi radialis, abductor pollicis brevis, abductor digiti minimi, quadriceps and tibialis anterior. But we did not recognise acute denervation change in needle EMG. Unfortunately, the patient refused a sural nerve biopsy. After admission, a colonoscopy examination was done and we ascertained the remission of his UC. We discontinued the 5-ASA on March 12, 1998. Three weeks later, the dysesthesia of his right leg recovered and DTR appeared in the upper extremities. Thereafter, muscular strength also recovered and his grip power increased from 18 to 28 kg in the right and from 25 to 32 kg in the left, and he could walk almost normally at this point. In the nerve conduction studies, the MCV were improved, but sural sensory nerve responses remained unrecordable (Table 1). In May 1998, he only had mild atrophy of the right arm and a mild disturbance of the vibration sensation in the left leg. Diarrhoea and abdominal pain were not reported. DISCUSSION 5-ASA is produced by colonic bacteria from SASP and metabolized by N-acetyltransferase 1 (NAT1) into acetyl-5-ASA (Fig. 2). SP is also produced from SASP and metabolized by N-acetyl-
Fig. 2
transferase 2 (NAT2) into acetyl-SP.11 Adverse reactions to SASP have been known to be caused by SP due to slow NAT2 activity.12;13 Enteric-coated 5-ASA was developed to reduce the side effects of SASP.14 The neuropathy of the present patient occurred after exposure to SASP; it persisted after changing to 5-ASA, and recovered gradually after 5-ASA was discontinued. This suggested that the neuropathy of this patient was associated with 5ASA. Woodward reported a case of polyneuropathy associated with 5-ASA,6 and cases of neuropathy after exposure to SASP have been reported.24 Although neurologic disorders associated with UC, such as neuropathy, myelopathy or myasthenia gravis have also been reported,7 the association of neuropathy with UC is uncommon and the pathogenesis is unknown.810 In the present patient, it is possible that the neuropathy was associated with UC but the symptoms continued to progress when UC was in remission and then began to improve after the discontinuation of 5ASA. The neuropathy associated with SASP or 5-ASA is reported to manifest mainly sensory symptoms and to begin to improve a few weeks after withdrawal of the drug.24;6 The present case showed a similar course. Most UC patients are treated with SASP or 5-ASA, thus some neuropathy associated with UC may develop from taking these drugs. We concluded that the neuropathy of the present patient was sensorimotor polyneuropathy because of his clinical symptoms and the results of the electrodiagnostic studies. Most drug-induced neuropathies involve axonal changes,15 based on the electrodiagnostic studies, the polyneuropathy of this patient could be also diagnosed dominant axonal change rather than demyelinated change. In conclusion, the neuropathy in the present patient with UC may have been caused by the medications used to treat UC.
The metabolism of salazosulphapyridine. 5-ASA, 5-aminosalicylic acid; NAT, N-acetyltransferase.
Journal of Clinical Neuroscience (2003) 10(3)
ª 2003 Elsevier Science Ltd. All rights reserved.
Cervical ependymoma presenting with brainstem and cerebellar signs
ACKNOWLEDGEMENTS We are grateful to Dr. S. Kusunoki, Department of Neurology, Tokyo University School of Medicine for the examination of serum autoantibodies against ganglioside, to Dr. M. Shibuya, Department of Physiology (II), Showa University School of Medicine, for advice on scientific writing, and to Mary Beth Shibuya for advice on medical English.
389
indicates the need to include cervical imaging well below the foramen magnum in these circumstances. ª 2003 Elsevier Science Ltd. All rights reserved. Journal of Clinical Neuroscience (2003) 10(3), 389–391 ª 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0967-5868(03)00008-0
Keywords: spinal cord ependymoma, oedema Received 31 August 2001 Accepted 19 December 2001
REFERENCES 1. Peppercorn MA, Goldman P. The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. J Pharmacol Exp Ther 1972; 181: 555–562. 2. Wallace JW. Neurotoxicity associated with a reduction to sulphasalazine. Practitioner 1979; 2: 276–278. 3. Price TR. Sensorimotor neuropathy with sulphasalazine. Postgrad Med J 1985; 61: 147–148. 4. Blin O, Sangla I, Jouglard J, Cottin C, Pellissier JF, Serratrice G. Axonal neuropathy and salazosulphapyridine: slow-acetylator phenotype. Rev Neurol (Paris) 1992; 148: 154–156. 5. Habal FM, Greenberg GR. Treatment of ulcerative colitis with oral 5-aminosalicylic acid including patients with adverse reactions to sulfasalazine. Am J Gastroenterol 1988; 83: 15–19. 6. Woodward DK. Peripheral neuropathy and mesalazine. BMJ 1989; 299: 1224. 7. Lossos A, River Y, Eliakim A, Steiner I. Neurologic aspects of inflammatory bowel disease. Neurology 1995; 45: 416–421. 8. Konagaya Y, Konagaya M, Takayanagi T. Chronic polyneuropathy and ulcerative colitis. Jpn J Med 1989; 28: 72–74. 9. Okiyama R, Yamada M, Tamaki M, Orimo S, Arai M. Mononeuropathy multiplex with ulcerative colitis. Intern Med 1993; 32: 651–654. 10. Chad DA, Smith TW, DeGirolami U, Hammer K. Perineuritis and ulcerative colitis. Neurology 1986; 36: 1377–1379. 11. Klotz U. Clinical pharmacokinetics of sulphasalazine, it’s metabolites and other prodrugs of 5-aminosalicylic acid. Clin Pharmacokinet 1985; 10: 285–302. 12. Das KM, Eastwood MA, McManus JPA, Sircus W. Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype. N Engl J Med 1973; 289: 491–495. 13. Azad Khan AK, Nurazzaman M, Truelove SC. The effect of the acetylator phenotype on the metabolism of sulphasalazine in man. J Med Genet 1983; 20: 30–36. 14. Hanauer SB, Stathopoulos G. Risk-benefit assessment of drugs used in the treatment of inflammatory bowel disease. Drug Safety 1991; 6: 192–219. 15. Le Quesne PM. Neuropathy due to drugs. In: Dyck PJ, Thomas PK (eds) Peripheral Neuropathy, First edn. Saunders, Philadelphia 1993; 1571–1581.
Cervical ependymoma presenting with brainstem and cerebellar signs: case report
Correspondence to: Roy G. Beran, Department of Neurology, Liverpool Hospital, Elizabeth Drive, Liverpool NSW 2170, Australia. Tel.: +02-98283646; Fax: +02-98283648; E-mail: [email protected]
INTRODUCTION This case report highlights the need to consider cervical pathology as a possible cause of intracranial signs and symptoms, despite there being no previous report of an ependymoma causing intracranial features purely consequent to extensive oedema. The ependyma is a single layer of epithelium lining the ventricular spaces of the brain and extending down the centre of the spinal cord. Ependymomas, which are generally slow-growing and histologically benign, are derived from this single layer of cells. Early in life (first 2 decades), they typically occur in the fourth ventricle, where they constitute between 5 and 10% of primary brain tumours in this age group. In later years, the most common location is the spinal cord, where they constitute a large proportion of primary intraspinal neoplasms.1;2 Microscopically, ependymomas are composed of cells with rather regular, round to oval or “carrot-shaped” nuclei with abundant granular chromatin. Between the nuclei there is a fine fibrillary background that may be very dense. Helpful diagnostic features include ependymal canals and rosettes, in which tumour cells create arrays that resemble ependymal canals, and perivascular ependymal pseudorosettes, in which there is a very dense array of long, delicate ependymal processes inserted into the wall of a blood vessel, producing a prominent nucleus-free halo around the vessel. Blepharoplasts, which are the basal bodies of cilia, are stained by PTAH and are pathognomonic if present. Immunocytochemically, about 50% of ependymomas can be shown to contain the neuroglial intermediate filament glial fibrillary acidic protein (GFAP). Most tumours are well-differentiated, but anaplastic tumours occur, the most anaplastic of which resemble glioblastomas.3 CASE REPORT
1 Domit A. Azar1 MBBS(HONS) MBBS(HONS), Roy G. Beran 2 Toos Sachinwalla FRANZCR
MD FRACP FRCP,
1 Department of Neurology, Liverpool Hospital, Sydney, Australia, 2Department of Radiology, Liverpool Hospital, Sydney, Australia
Summary This case report demonstrates cervical spinal cord pathology which presented with brainstem and cerebellar signs consequent to the peritumoural oedema that extended rostrally to the pontomedullary junction. A Medline search of the literature back to 1960 failed to produce any previous report of a cervical ependymoma presenting with brainstem and cerebellar signs purely consequent to oedema. This case highlights the need to look further afield when presented with the scenario of clinical features of a brainstem lesion with only oedema apparent on cranial imaging. It
ª 2003 Elsevier Science Ltd. All rights reserved.
A 50-year-old caucasian man presented with a 6 week history of gait disturbance, non-specific sensory symptoms throughout his body and pins and needles paraesthesia in both hands and feet. He described a “tingling” feeling in his legs, difficulty with manual dexterity such that he dropped objects and complained of incoordination. There was a past history of head injury from which he made a full recovery with no neurological deficit. Neurological examination revealed nystagmus of the abducted right eye with limited adduction of the left eye, suggesting an internuclear ophthalmoplegia due to a brainstem lesion. He had ataxia of gait, falling to the right, without other features of cerebellar disease such as dysmetria, dysarthria, dysdiadochokinesis or intention tremor. He reported non-specific sensory changes in the right lower limb which were neither dermatomal nor nerve-specific to provide extra localising features. The provisional diagnosis was of Journal of Clinical Neuroscience (2003) 10(3)
Fig. 3 Axial contrast-enhanced CT scan showing the large left cerebellopontine angle acoustic schwannoma. The internal auditory meatus is widened.
inadequate and even chaotic behaviour. We analyzed the various benign tumours reported to be associated with pathological laughter. Dumbbell shaped large trigeminal neurinoma is more common amongst these tumours.2;3 The combination of pressure over the brainstem and the medial temporal brain structures could be the probable mechanism of pathological laughter in these tumours. As tumours located entirely in the posterior fossa22–28 have been reported to result in pathological laughter, pressure or hump of the brainstem appears more crucial than pressure over the temporal brain. Considering that pathological laughter as a presenting symptom occurs only extremely rarely, a complex combination of factors must be essential for a tumour to cause pathological laughter. Both the acoustic schwannomas presented had a more medial location. It appears that compression of the brainstem at or just below the level of the tentorium producing a typical hump of the brainstem could be responsible for production of the symptom of pathological laughter. In majority of reported cases, the pathological laughter was completely abolished after the tumour resection. In the presented cases and those reported earlier,2;3;27 there was a well-defined dissection plane between the tumour and the brainstem. This suggests that it is only pressure or distortion of the neural structures rather than a permanent damage or a vascular insufficiency that initiated the chain of events. REFERENCES 1. Achari AN, Colover J. Posterior fossa tumours with pathological laughter. JAMA 1976; 235: 1469–1471. 2. Bhatjiwale MG, Goel A, Desai KI. Pathological laughter as a presenting symptom of trigeminal neurinoma. Case report. Neurol Med Chir (Tokyo) 1996; 36: 644–646. 3. Bhatjiwale MG, Nadkarni TD, Desai KI, Goel A. Pathological laughter as a presenting symptom of massive trigeminal neuromas: report of four cases. Neurosurgery 2000; 47: 469–471. 4. Matsuoka S, Aragaki Y, Numaguchi K, Hinokuma K. A case of angioblastic meningioma with pathological laughter – with special reference to laughter in brain tumour. Neurol Med Chir (Tokyo) 1977; 17: 195–201 [Japanese, with English abstract].
Journal of Clinical Neuroscience (2003) 10(3)
5. Matsuoka S, Yokota A, Yasukouchi H et al. Clival chordoma associated with pathological laughter. J Neurosurg 1993; 79: 428–433. 6. Monteil P, Cohadon F. Pathological laughing as a symptom of a tentorial edge tumour. J Neurol Neurosurg Psychiatry 1996; 60: 370. 7. Nadkarni TD, Goel A. Trochlear nerve neurinoma presenting as a pathological laughter. Br J Neurosurg 1999; 13: 212–213. 8. Cairns H. Mental disorders with tumours of the pons. Folia Psychiatr Neurol Jpn 1950; 53: 193–203. 9. Adams RD, Victor M, Ropper AH. The limbic lobes and the neurology of emotion. In: Adams RD, Victor M (eds) Principles of Neurology. sixth ed. McGraw Hill, New York 1997; 508–521. 10. Ironside R. Disorders of laughter due to brain lesions. Brain 1956; 79: 589–609. 11. Asfora WT, DeSalles AA, Abe M, Kjellberg RN. Is the syndrome of pathological laughing and crying a manifestation of pseudobulbar palsy? J Neurol Neurosurg Psychiatry 1989; 52: 523–525. 12. Couderq C, Drouineau J, Rosier MP, Alvarez A, Gil R, Neau JP. Pathological laughter after the brainstem infarction. Rev Neurol (Paris) 2000; 156: 281–284 [French, with English abstract]. 13. Kubik CS, Adams RD. Occlusion of the basilar artery: a clinical and pathological study. Brain 1946; 69: 73–121. 14. Black DW. Pathological laughter. A review of the literature. J Nerv Ment Dis 1982; 170: 67–71. 15. Tei H, Sakamoto Y. Pontine infarction due to basilar artery stenosis presenting as pathological laughter. Neuroradiology 1997; 39: 190–191. 16. Garg RK, Misra S, Verma R. Pathological laughter as heralding manifestation of left middle cerebral artery territory infarct. Case report and review of literature. Neurol India 2000; 48: 388–390. 17. Davison C, Kelman H. Pathological laughing and crying. Arch Neurol Psychiatry 1929; 42: 595–643. 18. Stern WE, Brown WJ. Pathological laughter. J Neurosurg 1957; 14: 129–139. 19. Gopinath SP. Pathological laughter. J Neurosurg 1994; 80: 596–597. 20. Gottwald W. Paroxyms of pathological laughter and crying. Med Welt 1982; 33: 622–626 [German]. 21. Pecker J, Delaitre R, Guy G, Faivre J. Pathological laughter in brain stem diseases. Rev Otoneuroophtalmol 1970; 42: 236–238. 22. Cantu RC. Importance of pathological laughing and/or crying as a sign of occurrence or recurrence of a tumour lying beneath the brainstem. J Nerv Ment Dis 1966; 143: 508–512. 23. Cantu RC, Drew JH. Pathological laughing and crying associated with a tumour ventral to the pons. Case report. J Neurosurg 1966; 24: 1024–1026. 24. Lal AP, Chandy MJ. Pathological laughter and brainstem glioma. J Neurol Neurosurg Psychiatry 1992; 55: 628–629. 25. Osumi Y, Yamadori A, Tamaki N. Case of ventrally situated brainstem meningioma associated with forced laughter. Rinsho Shinkeigaku 1976; 16: 715–720 [Japanese, with English abstract]. 26. Shafqat S, Elkund MSV, Chiocca EA, Takeoka M, Koroshetz WJ. Petroclival meningioma presenting with pathological laughter. Neurology 1998; 50: 1918–1919. 27. Muzumdar D, Agrahar P, Desai K, Goel A. Pathological laughter as a presenting symptom of petroclival meningioma – case report. Neurol Med Chir (Tokyo) 2001; 41: 505–507. 28. Stevenson GC, Stoney RJ, Perkins RK, Adams JF. A transcervical transclival approach to the ventral surface of the brainstem for removal of a clivus chordoma. J Neurosurg 1966; 24: 544–551. 29. Parvizi J, Anderson SW, Martin CO, Damasio H, Damasio AR. Pathological laughter and crying: a link to the cerebellum. Brain 2001; 124: 1708–1719.
Sensorimotor polyneuropathy with 5-aminosalicylic acid: a case report Kenjiro Ono1 MD, Kazuo Iwasa2 Masaharu Takamori3 MD
MD,
Hiroe Shirasaki1
MD,
1 Department of Neurology and Neurobiology of Aging, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8640, Japan, 2Department of Neurology, National Kanazawa Wakamatsu Hospital, Se-103-1 Wakamatsu-machi, Kanazawa, Ishikawa 920-1183, Japan, 3 Neurological Center, Kanazawa-Nishi Hospital, Kou-77 Kanazawa-kita-machi, Kanazawa, Ishikawa 920-0055, Japan
ª 2003 Elsevier Science Ltd. All rights reserved.
Sensorimotor polyneuropathy with 5-aminosalicylic acid
Summary A 69-year-old man with ulcerative colitis (UC) developed sensorimotor polyneuropathy. First, he received salazosulphapyridine (SASP) as treatment for the UC. The symptoms of UC disappeared immediately, but he developed skin eruptions and dysesthesia in his lower limbs. When SASP was changed to 5aminosalicyclic acid (5-ASA), his skin eruptions were resolved, however, he developed weakness and atrophy in his right arm as well as progressive worsening of the dysesthesia in his legs and gait disturbance. Deep tendon reflexes (DTR) were absent in all extremities. After 5-ASA was discontinued, the polyneuropathy symptoms recovered gradually. This clinical course suggests that the sensorimotor polyneuropathy may have been caused by 5-ASA. ª 2003 Elsevier Science Ltd. All rights reserved. Journal of Clinical Neuroscience (2003) 10(3), 386–389 ª 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0967-5868(03)00066-3
Keywords: sensorimotor polyneuropathy, ulcerative colitis, 5-aminosalicylic acid (5-ASA) Received 22 February 2002 Accepted 16 March 2002 Correspondence to: K. Ono MD, Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Tel.: +81-76-265-2290; Fax: +81-76-234-4253; E-mail: [email protected]
INTRODUCTION Ulcerative colitis (UC) is a nonspecific inflammatory disease of unknown aetiology, which usually affects the colonic mucosa and often produces erosions and ulcers. The treatments for UC are the administration of salazosulphapyridine (SASP) or 5-aminosalicylic acid (5-ASA) and steroid. SASP is known to be decomposed by enteric bacteria into sulphapyridine (SP) and 5ASA.1 Neuropathy that is associated with SASP has been documented,24 but neuropathy caused by 5-ASA has been rarely reported.5;6 Neurological disorders associated with UC, such as neuropathy, myelopathy or myasthenia gravis have been reported,7 however, the association of neuropathy with UC is
387
uncommon and the pathogenesis is unknown.810 We present a patient who developed sensorimotor polyneuropathy during treatment for UC, and this polyneuropathy recovered after the medication was discontinued.
CASE REPORT A 69 year old shopkeeper presented with abdominal pain and diarrhoea in May 1997. He was diagnosed as UC by colonoscopy and colonic biopsy. There was no family history of UC. Medication consisting of oral SASP 3 g/day was started in June 1997. His abdominal pain and diarrhoea improved immediately. One month after the start of SASP, he had skin eruptions and mild dysesthesia on his lower limbs (Fig. 1). A dermatologist confirmed the diagnosis of drug toxico-dermatitis. SASP was changed to 5-ASA 750 mg/day in July 1997. The skin eruptions disappeared after the drug was changed, but the dysesthesia of his lower limbs progressed and, in September 1997, he noticed muscle weakness in his right arm and leg. Five months after the initial onset of dysesthesia on his lower limbs, he noticed that he had muscle atrophy of his right arm and gait disturbance. When he was admitted to our hospital in March 1998, we did not recognise any abnormalities of his skin or abdomen by physical examination. On neurological examination, he had normal cranial nerve function and normal strength in the proximal muscles of the extremities. But his muscles were hypotonic, and his right arm and thenar muscle were atrophic. Manual muscle testing (MMT) revealed: distal right arm, 3/5; right hand, 3/5; left hand, 4þ =5; right peroneal muscle, 3/5 and bilateral toe-flexion, 3/5. Deep tendon reflexes (DTR) were absent bilaterally, and responses to plantar stimulus were flexion. Cerebellar examination was normal, dysesthesia was found in both feet but primarily on the right side; also, a decrease in distal vibration sensation was recognised in both legs. Romberg sign was negative. Gait was steppage and walking on heels was difficult. Laboratory testing showed normal blood data. Serum vitamin B1 , vitamin B12 and folic acid levels were normal. He had a normal glucose tolerance. He did not have serum autoantibodies against ganglioside, Hu, DNA or nuclear cells. N-transferase 2 phenotype was an intermediate acetylator of a normal activity type. Cerebrospinal fluid findings were normal. We could not find any malignancy. Nerve
Fig. 1 Clinical course of the patient of sensorimotor polyneuropathy with 5-ASA. After withdrawal of 5-ASA, this neuropathy recovered gradually. SASP, salazosulphapyridine; 5-ASA, 5-aminosalicylic acid.
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Journal of Clinical Neuroscience (2003) 10(3)
388 Ono et al.
Table 1
Motor and sensory nerve conduction studies
Tested nerve
Motor nerves R median Wrist–elbow Elbow–axilla R ulnar Wrist–elbow Elbow–axilla R peroneal R tib. pos. Sensory nerves R median R ulnar R sural
12th March 1998
18th May 1998
dAMP (lV)
CV (m/s)
dAMP (lV)
9.8 (wrist) 9.8 (elbow)
52.2 52.9a
11.1 8.2
59.1 66.4
6.6 (wrist) 5.5 (elbow) 5.0 11.5
54.1 45.1a 39.2a 38.5a
6.5 5.5 5.9 9.6
59.1 59.2 45.9 46.1
10.0 (wrist) 7.1 (wrist) Not detected
42.2 35.4
9.6 9.0 Not detected
CV (m/s)
42.8 41.0
dAMP, distal amplitude of CMAPs or SNAPs; CMAPs, compound muscle action potentials; SNAPs, sensory nerve action potentials; CV, conduction velocity; R, right; tib. pos., posterior tibial nerve. a < smaller than normal range.
conduction studies showed mildly decreased motor conduction velocities (MCV) in the right median, ulnar, peroneal and posterior tibial nerves. Sural sensory nerve responses were unrecordable bilaterally (Table 1). F-Wave frequencies and latencies in the right median, ulnar, peroneal and posterior tibial nerves were within normal range. Needle EMG demonstrated an increased duration and amplitude, and the appearance of polyphasic motor unit and giant spike in right triceps, brachioradialis, extensor carpi radialis, abductor pollicis brevis, abductor digiti minimi, quadriceps and tibialis anterior. But we did not recognise acute denervation change in needle EMG. Unfortunately, the patient refused a sural nerve biopsy. After admission, a colonoscopy examination was done and we ascertained the remission of his UC. We discontinued the 5-ASA on March 12, 1998. Three weeks later, the dysesthesia of his right leg recovered and DTR appeared in the upper extremities. Thereafter, muscular strength also recovered and his grip power increased from 18 to 28 kg in the right and from 25 to 32 kg in the left, and he could walk almost normally at this point. In the nerve conduction studies, the MCV were improved, but sural sensory nerve responses remained unrecordable (Table 1). In May 1998, he only had mild atrophy of the right arm and a mild disturbance of the vibration sensation in the left leg. Diarrhoea and abdominal pain were not reported. DISCUSSION 5-ASA is produced by colonic bacteria from SASP and metabolized by N-acetyltransferase 1 (NAT1) into acetyl-5-ASA (Fig. 2). SP is also produced from SASP and metabolized by N-acetyl-
Fig. 2
transferase 2 (NAT2) into acetyl-SP.11 Adverse reactions to SASP have been known to be caused by SP due to slow NAT2 activity.12;13 Enteric-coated 5-ASA was developed to reduce the side effects of SASP.14 The neuropathy of the present patient occurred after exposure to SASP; it persisted after changing to 5-ASA, and recovered gradually after 5-ASA was discontinued. This suggested that the neuropathy of this patient was associated with 5ASA. Woodward reported a case of polyneuropathy associated with 5-ASA,6 and cases of neuropathy after exposure to SASP have been reported.24 Although neurologic disorders associated with UC, such as neuropathy, myelopathy or myasthenia gravis have also been reported,7 the association of neuropathy with UC is uncommon and the pathogenesis is unknown.810 In the present patient, it is possible that the neuropathy was associated with UC but the symptoms continued to progress when UC was in remission and then began to improve after the discontinuation of 5ASA. The neuropathy associated with SASP or 5-ASA is reported to manifest mainly sensory symptoms and to begin to improve a few weeks after withdrawal of the drug.24;6 The present case showed a similar course. Most UC patients are treated with SASP or 5-ASA, thus some neuropathy associated with UC may develop from taking these drugs. We concluded that the neuropathy of the present patient was sensorimotor polyneuropathy because of his clinical symptoms and the results of the electrodiagnostic studies. Most drug-induced neuropathies involve axonal changes,15 based on the electrodiagnostic studies, the polyneuropathy of this patient could be also diagnosed dominant axonal change rather than demyelinated change. In conclusion, the neuropathy in the present patient with UC may have been caused by the medications used to treat UC.
The metabolism of salazosulphapyridine. 5-ASA, 5-aminosalicylic acid; NAT, N-acetyltransferase.
Journal of Clinical Neuroscience (2003) 10(3)
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Cervical ependymoma presenting with brainstem and cerebellar signs
ACKNOWLEDGEMENTS We are grateful to Dr. S. Kusunoki, Department of Neurology, Tokyo University School of Medicine for the examination of serum autoantibodies against ganglioside, to Dr. M. Shibuya, Department of Physiology (II), Showa University School of Medicine, for advice on scientific writing, and to Mary Beth Shibuya for advice on medical English.
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indicates the need to include cervical imaging well below the foramen magnum in these circumstances. ª 2003 Elsevier Science Ltd. All rights reserved. Journal of Clinical Neuroscience (2003) 10(3), 389–391 ª 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0967-5868(03)00008-0
Keywords: spinal cord ependymoma, oedema Received 31 August 2001 Accepted 19 December 2001
REFERENCES 1. Peppercorn MA, Goldman P. The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. J Pharmacol Exp Ther 1972; 181: 555–562. 2. Wallace JW. Neurotoxicity associated with a reduction to sulphasalazine. Practitioner 1979; 2: 276–278. 3. Price TR. Sensorimotor neuropathy with sulphasalazine. Postgrad Med J 1985; 61: 147–148. 4. Blin O, Sangla I, Jouglard J, Cottin C, Pellissier JF, Serratrice G. Axonal neuropathy and salazosulphapyridine: slow-acetylator phenotype. Rev Neurol (Paris) 1992; 148: 154–156. 5. Habal FM, Greenberg GR. Treatment of ulcerative colitis with oral 5-aminosalicylic acid including patients with adverse reactions to sulfasalazine. Am J Gastroenterol 1988; 83: 15–19. 6. Woodward DK. Peripheral neuropathy and mesalazine. BMJ 1989; 299: 1224. 7. Lossos A, River Y, Eliakim A, Steiner I. Neurologic aspects of inflammatory bowel disease. Neurology 1995; 45: 416–421. 8. Konagaya Y, Konagaya M, Takayanagi T. Chronic polyneuropathy and ulcerative colitis. Jpn J Med 1989; 28: 72–74. 9. Okiyama R, Yamada M, Tamaki M, Orimo S, Arai M. Mononeuropathy multiplex with ulcerative colitis. Intern Med 1993; 32: 651–654. 10. Chad DA, Smith TW, DeGirolami U, Hammer K. Perineuritis and ulcerative colitis. Neurology 1986; 36: 1377–1379. 11. Klotz U. Clinical pharmacokinetics of sulphasalazine, it’s metabolites and other prodrugs of 5-aminosalicylic acid. Clin Pharmacokinet 1985; 10: 285–302. 12. Das KM, Eastwood MA, McManus JPA, Sircus W. Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype. N Engl J Med 1973; 289: 491–495. 13. Azad Khan AK, Nurazzaman M, Truelove SC. The effect of the acetylator phenotype on the metabolism of sulphasalazine in man. J Med Genet 1983; 20: 30–36. 14. Hanauer SB, Stathopoulos G. Risk-benefit assessment of drugs used in the treatment of inflammatory bowel disease. Drug Safety 1991; 6: 192–219. 15. Le Quesne PM. Neuropathy due to drugs. In: Dyck PJ, Thomas PK (eds) Peripheral Neuropathy, First edn. Saunders, Philadelphia 1993; 1571–1581.
Cervical ependymoma presenting with brainstem and cerebellar signs: case report
Correspondence to: Roy G. Beran, Department of Neurology, Liverpool Hospital, Elizabeth Drive, Liverpool NSW 2170, Australia. Tel.: +02-98283646; Fax: +02-98283648; E-mail: [email protected]
INTRODUCTION This case report highlights the need to consider cervical pathology as a possible cause of intracranial signs and symptoms, despite there being no previous report of an ependymoma causing intracranial features purely consequent to extensive oedema. The ependyma is a single layer of epithelium lining the ventricular spaces of the brain and extending down the centre of the spinal cord. Ependymomas, which are generally slow-growing and histologically benign, are derived from this single layer of cells. Early in life (first 2 decades), they typically occur in the fourth ventricle, where they constitute between 5 and 10% of primary brain tumours in this age group. In later years, the most common location is the spinal cord, where they constitute a large proportion of primary intraspinal neoplasms.1;2 Microscopically, ependymomas are composed of cells with rather regular, round to oval or “carrot-shaped” nuclei with abundant granular chromatin. Between the nuclei there is a fine fibrillary background that may be very dense. Helpful diagnostic features include ependymal canals and rosettes, in which tumour cells create arrays that resemble ependymal canals, and perivascular ependymal pseudorosettes, in which there is a very dense array of long, delicate ependymal processes inserted into the wall of a blood vessel, producing a prominent nucleus-free halo around the vessel. Blepharoplasts, which are the basal bodies of cilia, are stained by PTAH and are pathognomonic if present. Immunocytochemically, about 50% of ependymomas can be shown to contain the neuroglial intermediate filament glial fibrillary acidic protein (GFAP). Most tumours are well-differentiated, but anaplastic tumours occur, the most anaplastic of which resemble glioblastomas.3 CASE REPORT
1 Domit A. Azar1 MBBS(HONS) MBBS(HONS), Roy G. Beran 2 Toos Sachinwalla FRANZCR
MD FRACP FRCP,
1 Department of Neurology, Liverpool Hospital, Sydney, Australia, 2Department of Radiology, Liverpool Hospital, Sydney, Australia
Summary This case report demonstrates cervical spinal cord pathology which presented with brainstem and cerebellar signs consequent to the peritumoural oedema that extended rostrally to the pontomedullary junction. A Medline search of the literature back to 1960 failed to produce any previous report of a cervical ependymoma presenting with brainstem and cerebellar signs purely consequent to oedema. This case highlights the need to look further afield when presented with the scenario of clinical features of a brainstem lesion with only oedema apparent on cranial imaging. It
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A 50-year-old caucasian man presented with a 6 week history of gait disturbance, non-specific sensory symptoms throughout his body and pins and needles paraesthesia in both hands and feet. He described a “tingling” feeling in his legs, difficulty with manual dexterity such that he dropped objects and complained of incoordination. There was a past history of head injury from which he made a full recovery with no neurological deficit. Neurological examination revealed nystagmus of the abducted right eye with limited adduction of the left eye, suggesting an internuclear ophthalmoplegia due to a brainstem lesion. He had ataxia of gait, falling to the right, without other features of cerebellar disease such as dysmetria, dysarthria, dysdiadochokinesis or intention tremor. He reported non-specific sensory changes in the right lower limb which were neither dermatomal nor nerve-specific to provide extra localising features. The provisional diagnosis was of Journal of Clinical Neuroscience (2003) 10(3)