13 Multiple Sclerosis MULTIPLE SCLEROSIS 133 OPTIC NEURITIS 136 SYRINGOMYELIA AND SYRINGOBULBIA 137 TRANSVERSE MYELITIS 139 Multiple Sclerosis dysfunction (vertigo), trigeminal neuralgia (stabbing pain in the cheeks), and optic nerve dysfunction (left painful visual loss, afferent pupillary defect). Vignette Differential Diagnosis During the past six months a 22-year-old student experienced several episodes of sudden stabbing Several categories of neurological disorders can be con- pain in both cheeks, especially around her eyes. The sidered in the differential diagnosis of multifocal pathol- pain was severe and debilitating, making her un- ogy, including able to talk for a few seconds. For the last two • Demyelinating disorders: multiple sclerosis. months her gait has been unsteady and cautious, at • Infectious and inflammatory disorders: acute dissemi- times veering to the left. She has also complained of dizziness, described as “severe spinning” for a nated encephalomyelitis, HIV, Lyme disease, systemic few minutes, which did not improve with eye clos- lupus erythematosus, Sjo¨gren syndrome. ing. One year ago she suffered painful loss of vision • Vascular disorders: cerebral vasculitis, multiple em- in her left eye, which partially resolved within 1 boli, familial cavernous hemangiomas. week. She had no history of smoking, alcohol, or • Cerebral malformations: Chiari malformation. drug abuse. Her mother had migraine headache. • Space-occupying lesions: primary lymphoma of the The neurological examination indicates a normal brain, multiple metastases. mental status. The right pupil promptly constricts • Hereditary disorders: leukodystrophies, mitochondrial on illumination. As the light is rapidly moved to the disorders. left, the left pupil dilates. Mild left hemiparesis is In a young adult presenting with focal neurological also noted. Gait is ataxic. deficits separated in both time and space, a demyelinating disorder such as multiple sclerosis (MS) ranks high on Summary A 22-year-old woman experiencing several the list of possible diagnoses. episodes of pain in the cheeks, unsteady gait, vertigo, and Trigeminal neuralgia in multiple sclerosis is much left visual loss that partially recovered. Neurological ex- more often bilateral (Matthews) and occurs approxi- amination shows a left afferent pupillary defect, left mately in 1 percent of patients and usually at an earlier hemiparesis, and ataxic gait. age than the idiopathic form. Corticospinal tract involvement is part of the initial Localization attack of MS in 32 to 41 percent of patients (Miller). It is important to localize the lesion and determine Lower extremities weakness seems more common than whether it is focal, multifocal, or diffuse. A multifocal upper extremities involvement and can be unilateral. lesion is represented by two or more focal lesions dis- Cerebellar involvement is also common in multiple tributed randomly. In the vignette presented, the patient sclerosis and is indicated by the manifestations of ataxia, clearly has multifocal lesions disseminated in space and incoordination, intention tremor, dysarthria, and so on. time. Therefore we can identify pyramidal signs (left Cerebellar ataxia as an early sign can predict a bad hemiparesis), cerebellar signs (gait ataxia), vestibular prognosis without significant remission (Matthews). 133 134 13. Multiple Sclerosis Vertigo can occur during the initial attack of MS or Systemic lupus erythematosus (SLE) can simulate MS during relapse. and present some diagnostic difficulties when the neu- A relative afferent pupillary defect such as the one de- rological symptoms precede the signs of systemic in- scribed in the vignette suggests optic nerve pathology and volvement. Lupus could be confused with MS when it consists of a relative decrease in pupillary constriction to presents with signs of optic neuritis combined with spinal light stimulation of the affected eye. cord dysfunction (Matthews). The most common mani- It is important to discuss the differential diagnosis. festations of cerebral involvement in SLE are usually psy- Other conditions that can be disseminated in space and chiatric, such as psychosis, depression, delusions, and sometimes in time may simulate MS. Infectious, post- hallucinations (Aminoff). Seizures, aseptic meningitis, infectious, and inflammatory disorders are important and movement disorders rather than signs suggestive of considerations. white matter dysfunction are also described. Laboratory Acute disseminated encephalomyelitis (ADEM) can be studies of immune function will complete the diagnosis. easily ruled out from the vignette. This disorder is char- Sjo¨gren’s syndrome, characterized by xerostomia, xe- acterized by widespread manifestations that reflect in- rophtalmia, and arthritis, can rarely affect the nervous volvement of multifocal areas such as cerebrum, brain- system (less than 10% of patients) (Aminoff). stem, cerebellum, optic nerve, and spinal cord. A history Behc¸et’s disease can present with multifocal cerebral of upper respiratory or other viral infections or immuni- symptoms but usually the typical ocular lesions and oral zation precedes the onset of neurological symptoms, and genital ulcers are antecedent or accompany the neu- characterized by fever, headache, meningeal signs, al- rological symptoms. Occasionally, though, they can occur tered consciousness, convulsions, ataxia, myoclonus, later (Matthew). Neurological signs and symptoms are paraplegia, sphincteric dysfunction, and so on. Children seen in 4 to 29 percent of patients (Aminoff). Signs of are preferentially affected more than adults. Varicella and central nervous system involvement include hemiparesis, unidentified upper respiratory tract viral causes are prob- ataxia, seizures, pseudobulbar palsy, spinal cord dysfunc- ably the major preceding infections causing ADEM in tion and can manifest a fluctuating course mimicking MS. North America (Munsat). A mortality up to 20 percent Sarcoidosis can also be responsible for a multifocal has been reported (Matthews) and neurological sequelae neurological pathology with involvement of the optic in surviving cases vary from spinal cord dysfunction to nerve, brainstem, cerebral hemispheres, and spinal cord, mental retardation and epilepsy. but only rarely these are the first signs and some typical The relapsing form of ADEM can simulate MS and features such as diabetes insipidus, hydrocephalus, and sometimes creates diagnostic difficulties. Also confusing peripheral neuropathy not expected with MS help the dif- is when MS presents with an acute fulminating form. ferential diagnosis. Also, sarcoidosis more commonly The examination of the CSF may show increased IgG than MS may cause anosmia, facial palsy, deafness, and and myelin basic protein in both disorders but oligoclonal progressive optic atrophy (Matthew). Sarcoidosis is a sys- bands are less commonly found in ADEM. The MRI of temic disorder that affects several organs, particularly the brain shows multifocal white matter lesions hyper- lymphonodes, lungs, skin, eyes, salivary glands, and so intense on T2 and does not clearly differentiate between MS and ADEM. on, and a positive diagnosis is based on the demonstration Other infections and inflammatory disorders also need of the characteristic noncaseating granuloma. to be considered. AIDS also needs to be ruled out because it can cause Lyme disease is an important part of the differential widespread neurological involvement usually associated diagnosis because it can simulate MS, particularly when with other systemic manifestations. it presents with signs of multifocal cerebral and spinal Central nervous system vasculitis that is restricted to cord dysfunction (encephalomyelitis). On the other hand, the CNS without systemic manifestations can cause mul- the most common presentation in Lyme disease is that of tifocal neurological signs but is a rare disorder, and head- a meningoencephalitis (Paty and Ebers) and it is very ache and changes in mental status are usually prominent. unlikely that such an infection would manifest with a typ- The diagnosis is based on angiographic findings and brain ical MS-like picture characterized by isolated episodes of biopsy. CNS dysfunction separated by months or years (Miller). Cerebrovascular disease, particularly multiple emboli, In Lyme disease, the history of prior living or visiting an can be part of the differential diagnosis of lesions dissem- endemic area, erythema migrans when demonstrated, ex- inated in space and time. The vignette does not suggest traneurological and systemic manifestations, such as ar- any risk factors for embolic stroke, which in a young thritis, carditis, generalized malaise, fatigue, and so on, person are usually represented by cardiac disorders, either positive serology, and CSF studies can help make the congenital or acquired. Other risk factors for ischemic or correct diagnosis. hemorrhagic events are also not indicated in the vignette Multiple Sclerosis 135 (vasculopathies, coagulopathies, Moya Moya, pregnancy, Laboratory Data puerperium, use of illicit drugs, oral contraceptive med- ications, hematological disorders, such as antithrombin The examination of the cerebrospinal fluid can support III, protein C and S deficiency, and antiphospholipid an- the diagnosis of MS and demonstrate characteristic, but tibody syndrome, sickle cell anemia, and so on). not specific, abnormalities, which can also be observed Cerebral malformations such as Arnold-Chiari malfor- with other pathology.