Article Text

Devic type multiple sclerosis in an 81 year old woman
  1. S M STAUGAITIS
  1. Department of Pathology, Division of Neuropathology, College of Physicians and Surgeons of Columbia University, New York, USA
  2. Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, USA
  3. Departments of Neurology and Public Health (Epidemiology), College of Physicians and Surgeons of Columbia University, New York, USA
  4. Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, USA
  5. Departments of Pathology (Division of Neuropathology) and Psychiatry, College of Physicians and Surgeons of Columbia University, and Department of Neuroscience (Division of Neuropathology), New York State Psychiatric Institute, New York, USA
  1. Dr Andrew J Dwork, Department of Neuroscience, New York State Psychiatric Institute, Unit 62, 722 West 168th Street, New York, NY 10032, USA. Telephone 001 212 543 5563; fax 001 212 543 5769; email: ajd6{at}columbia.edu
  1. J K ROBERTS
  1. Department of Pathology, Division of Neuropathology, College of Physicians and Surgeons of Columbia University, New York, USA
  2. Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, USA
  3. Departments of Neurology and Public Health (Epidemiology), College of Physicians and Surgeons of Columbia University, New York, USA
  4. Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, USA
  5. Departments of Pathology (Division of Neuropathology) and Psychiatry, College of Physicians and Surgeons of Columbia University, and Department of Neuroscience (Division of Neuropathology), New York State Psychiatric Institute, New York, USA
  1. Dr Andrew J Dwork, Department of Neuroscience, New York State Psychiatric Institute, Unit 62, 722 West 168th Street, New York, NY 10032, USA. Telephone 001 212 543 5563; fax 001 212 543 5769; email: ajd6{at}columbia.edu
  1. R L SACCO
  1. Department of Pathology, Division of Neuropathology, College of Physicians and Surgeons of Columbia University, New York, USA
  2. Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, USA
  3. Departments of Neurology and Public Health (Epidemiology), College of Physicians and Surgeons of Columbia University, New York, USA
  4. Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, USA
  5. Departments of Pathology (Division of Neuropathology) and Psychiatry, College of Physicians and Surgeons of Columbia University, and Department of Neuroscience (Division of Neuropathology), New York State Psychiatric Institute, New York, USA
  1. Dr Andrew J Dwork, Department of Neuroscience, New York State Psychiatric Institute, Unit 62, 722 West 168th Street, New York, NY 10032, USA. Telephone 001 212 543 5563; fax 001 212 543 5769; email: ajd6{at}columbia.edu
  1. J R MILLER
  1. Department of Pathology, Division of Neuropathology, College of Physicians and Surgeons of Columbia University, New York, USA
  2. Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, USA
  3. Departments of Neurology and Public Health (Epidemiology), College of Physicians and Surgeons of Columbia University, New York, USA
  4. Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, USA
  5. Departments of Pathology (Division of Neuropathology) and Psychiatry, College of Physicians and Surgeons of Columbia University, and Department of Neuroscience (Division of Neuropathology), New York State Psychiatric Institute, New York, USA
  1. Dr Andrew J Dwork, Department of Neuroscience, New York State Psychiatric Institute, Unit 62, 722 West 168th Street, New York, NY 10032, USA. Telephone 001 212 543 5563; fax 001 212 543 5769; email: ajd6{at}columbia.edu
  1. A J DWORK
  1. Department of Pathology, Division of Neuropathology, College of Physicians and Surgeons of Columbia University, New York, USA
  2. Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, USA
  3. Departments of Neurology and Public Health (Epidemiology), College of Physicians and Surgeons of Columbia University, New York, USA
  4. Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, USA
  5. Departments of Pathology (Division of Neuropathology) and Psychiatry, College of Physicians and Surgeons of Columbia University, and Department of Neuroscience (Division of Neuropathology), New York State Psychiatric Institute, New York, USA
  1. Dr Andrew J Dwork, Department of Neuroscience, New York State Psychiatric Institute, Unit 62, 722 West 168th Street, New York, NY 10032, USA. Telephone 001 212 543 5563; fax 001 212 543 5769; email: ajd6{at}columbia.edu

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An 81 year old woman presented after several transient episodes of dizziness and nausea. One episode was associated with right arm dysmetria. She denied previous neurological symptoms. Her medical history was relevant for myocardial infarction, two coronary artery bypass grafts, and Hashimoto’s thyroiditis. Brain MRI showed abnormal signal intensities which were attributed to cerebrovascular disease and she was treated with ticlopidine. Several months later, she had an influenza vaccination and one month afterwards she developed bilateral foot weakness and numbness. These symptoms progressed over three days to complete paraplegia, a thoracic sensory level, and urinary incontinence. No abnormalities were seen in the spinal cord on MRI. Over the next two months, sensation and bladder control improved and she could walk with a frame. Six months later, her spinal cord symptoms recurred; MRI at this time showed a cavitary lesion that extended from T2 to T10 with peripheral enhancement. Brain MRI showed multiple abnormal white matter signal intensities.

Cerebrospinal fluid contained 10 leucocytes/mm3 (70% lymphocytes, 20% monocytes, 10% polymorphonuclear leucocytes), total protein was 100 mg/dl, IgG/total protein was 16%, and oligoclonal bands were more intense in CSF than in serum. Complete blood count, chemistry profile, thyroid function tests, erythrocyte sedimentation rate, and an extensive investigation for autoimmune or inflammatory diseases were unrevealing. Doppler studies showed 80%-99% stenosis of the right carotid artery and<40% stenosis of the left. She was treated with dexamethasone (4 mg every six hours for 10 days) for a presumed inflammatory demyelinating disease, with no improvement in her neurological condition. She was transferred to a nursing home.

Two months later, she developed vertigo, nausea, blurred vision, and right face and arm weakness. Her symptoms rapidly progressed to tetraplegia, facial and oral weakness, visual loss, and lethargy. T2 weighted MRI images of her head and neck showed a diffuse high signal in the cervical spinal cord and medulla, and foci of increased signal intensity in white matter of the cerebral hemispheres and left cerebellum. The oligoclonal band pattern was similar to the previous study. High dose intravenous methylprednisolone produced no improvement. Her condition deteriorated and she died one month later.

The brain and spinal cord were fixed for 10 days in 10% formalin. Representative sections were treated with haematoxylin and eosin, Luxol fast blue/periodic acid-Schiff, and modified Bielschowsky stains. The cerebral blood vessels showed minimal atherosclerosis. Gross examination of the brain showed three periventricular plaques. The spinal cord showed softening with yellow discolouration and focal cavitation from T3 to T9. Microscopical examination disclosed extensive demyelination and necrosis. The most severe pathology was in the midthoracic region, where there was nearly total replacement of the parenchyma by a cavitary lesion containing numerous small blood vessels, foamy macrophages, and scattered lymphocytes. The cervical spinal cord showed microscopical foci of early demyelination in the posterior columns. The lumbar and sacral regions were uninvolved. The optic nerves and chiasm showed extensive demyelination with relative preservation of axons. Demyelinated plaques were also seen in the periventricular white matter, corpus callosum, basis pontis, pyramidal tracts, and deep cerebellar white matter. They displayed varying degrees of maturity, from small perivenous foci to large chronic active plaques (figure).

(A) Acute, microscopical perivascular plaque with lymphocytes and macrophages in the cerebellum (Luxol fast blue/periodic acid-Schiff, originally×100). (B) Chronic plaque in basis pontis. The edge of the plaque forms an abrupt interface with normally myelinated white matter (Luxol fast blue/periodic acid-Schiff, originally ×100).

The clinical and pathological features of this case are characteristic of Devic’s type of multiple sclerosis1; however, because of the patient’s advanced age, other diagnoses were considered. The major consideration was acute disseminated encephalomyelitis (ADEM), triggered by an immunisation for influenza.1 2 This possibility is excluded for two reasons: (1) the patient sought treatment for her neurological problems before the immunisation; (2) neither the clinical course nor pathological findings are characteristic of postimmunisation or postinfectious ADEM.

ADEM is typically a monophasic illness characterised pathologically by small, perivenular lesions, all of the same age.1 2Rarely, it may recur either with similar symptoms (“relapsing”) or with different symptoms referable to new CNS lesions (“multiphasic”, MDEM).1-3 Both multiple sclerosis and MDEM may show demyelinated lesions of varying ages; however, their topography on MRI often differs.3 In MDEM, the lesions are typically lobar or globular, whereas periventricular and callosal lesions, almost invariably present in multiple sclerosis, are rare. In the current case, the distribution of lesions by MRI and at necropsy is not characteristic for MDEM.

Most patients with multiple sclerosis present between the age of 20 and 50 years, but the onset in older people is well documented.4 As more people are living to an advanced age, it is reasonable to expect that more cases will appear. Clinically, many patients presenting at advanced ages have a more rapidly evolving course with predominantly motor deficits and spinal cord involvement, but the more typical progression may also be seen in this age group. The oldest presentation of multiple sclerosis previously reported was at the age of 69 and also had clinical and pathological features of Devic type multiple sclerosis.5

Devic’s syndrome, or neuromyelitis optica, is defined as the onset of acute transverse myelitis and optic neuritis within a short period. Whether neuromyelitis optica is a form of multiple sclerosis or a separate entity has been debated extensively. Most recently a group of eight patients aged 22–73 years with neuromyelitis optica but without clinical or histological evidence of brain involvement were reported.6 The authors suggested that these findings show that Devic’s neuromyelitis optica is a separate entity. The pathological features in the spinal cord and optic nerve presented here are similar to this previous report; however, our patient also had numerous typical multiple sclerosis plaques in the brain. In our case, Devic’s syndrome is clearly a form of multiple sclerosis. This case represents the oldest reported onset of multiple sclerosis and should serve to remind clinicians that this disease can occur at any age.

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