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Home , Dissociated sensory loss, Myelitis, Syringobulbia

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MULTIPLE SCLEROSIS 133 OPTIC NEURITIS 136 AND 137 TRANSVERSE 139

Multiple Sclerosis dysfunction (vertigo), trigeminal neuralgia (stabbing in the cheeks), and 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 , HIV, , systemic few minutes, which did not improve with eye clos- 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 . • Space-occupying lesions: primary lymphoma of the The neurological examination indicates a normal , 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 , 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 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). , aseptic , 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 . 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, , 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 involvement include hemiparesis, unidentified upper respiratory tract viral causes are prob- ataxia, seizures, , 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 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, , cerebral hemispheres, and spinal cord, mental retardation and . but only rarely these are the first signs and some typical The relapsing form of ADEM can simulate MS and features such as insipidus, , 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 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 . 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 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 (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). , 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 , which in a young thritis, carditis, generalized , 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 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. Cell count may show a mononu- 3 mation can present with multiple neurological signs dis- clear pleocytosis (10 to 50 mm ). Red blood cell and glu- seminated in space and referable to the cerebellum, upper cose content are normal. The total protein level can be cervical cord, and brainstem but some clinical features mildly elevated, but an abnormally high level (over 100 are characteristics such as pain in the occipital cervical mg/dl) may be suspicious of pathology other than MS. and upper limb area, hydrosyringomyelia with dissoci- There is an increased level of immunoglobulins in the ated sensory loss, nystagmus, predominantly vertical, and CSF, primarily IgG, which represent over 13 percent of so on. The diagnosis can be difficult and MS should be the total proteins in 70 percent of clinically definite MS ruled out in those patients presenting with progressive (Paty and Ebers). cerebellar and limb ataxia, spastic weakness, dysarthria, The IgG index, which is an indication of IgG produc- nystagmus, and so on. tion in the CSF, is determined by the ratios of IgG and Neoplastic disorders (multiple metastases, primary albumin in the CSF and serum. The presence of oligo- CNS lymphoma, remote effect of carcinoma such as para- clonal bands, which is characterized by the demonstration neoplastic cerebellar degeneration with limbic encepha- of two or more distinct IgG bands in the gamma region litis and optic neuritis) are obviously and easily ruled out of the electrophoresis, is found in 85 to 95 percent of from the vignette, but are mentioned because they can clinically definite MS (Paty and Ebers). Oligoclonal occasionally resemble MS presenting with neurological bands are not specific for MS but can be detected in pa- signs and symptoms disseminated in space and time. tients with acute and chronic infections, such as menin- Finally, we will very briefly consider hereditary dis- gitis and , and also chronic neuropathies, sar- orders, such as leukodystrophies, mitochondrial disor- coidosis, and so on. The myelin basic protein content and ders, and dominantly inherited ataxias. Adrenoleukodys- to myelin basic protein are nonspecific diag- trophy typically presents during childhood and rarely can nostic tests and have been used in some laboratories as be confused for MS. Adrenomyeloneuropathy that man- an indication of active disease. ifests in young adults can have signs of spinal cord dys- Magnetic resonance imaging is a very important test function usually in combination with peripheral neurop- for detecting MS abnormalities and can demonstrate athy and adrenal insufficiency. high-intensity periventricular lesions on T2-weighted im- Mitochondrial disorders can have multifocal involve- ages of different sizes from a few millimeters to centi- ment, but typically include signs of myopathy, peripheral meters, and Gd-DTPA enhancement with inflammatory neuropathy, exercise intolerance, unexplained headache activity. MRI criteria that are highly indicative of MS as and vomiting, hearing loss, dysmorphic features, and so described by Rudick include the presence of more than on that may point to the correct diagnosis. four white matter lesions equal or larger than 3 mm or The hereditary spinocerebellar ataxias are readily dis- three lesions and one adjacent to the ventricles, lesions tinguished from multiple sclerosis by their chronic pro- having a diameter of 6 mm or more, ovoid lesions bor- gression, insidious onset, family history, symmetrical dis- dering the ventricles, lesions involving the corpus cal- tribution, and associated abnormalities, neurological and losum or brainstem, and ring-like enhancing lesions with nonneurological such as reflex loss, skeletal deformities, Gd-DPTA. heart dysfunction, and so on. Some basic laboratory tests, such as CBC, ESR, ANA,

and B12 are always obtained to rule out other pathology. In selective cases, specific laboratory screening tests are Diagnosis performed such as Lyme titer, HIV,HTLV-1, antineuronal Several diagnostic criteria have been used to classify MS antibodies, thyroid function tests, very-low-chain fatty into clinically definite, probable, or possible. The clinical acids, and so on. Evoked potentials (VER, BAER, SEPs) diagnosis of definitive MS is based on the age of presen- are still obtained in many laboratories. tation (10 to 59 years according to Poser) (The Washing- ton Committee criteria); two attacks separated in time and Treatment space or two attacks with one clinical and one paraclinical evidence of lesion (where paraclinical indicates abnormal The treatment of MS is one of the most important issues findings on neuroimaging studies, evoked potentials, and in and a fundamental oral board question. It urodynamic studies). can be easily classified into treatment of acute relapse and 136 13. Multiple Sclerosis treatment of prevention of relapses and accumulation of Optic Neuritis deficits.

Treatment of Acute Relapse Vignette A relapse is defined as the occurrence of a new neuro- logical deficit or the exacerbation of a preexisting deficit A 35-year-old social worker woke up with right of at least 24 hour’s duration and not caused by other retroorbital pain and blurry vision. The pain in- pathology. The use of intravenous steroids in acute re- creased with eye movements, particularly in ex- lapse is particularly indicated in patients whose exacer- treme of gaze. On examination visual acuity was bation creates a significant neurological impairment. In- 20/20 on the left and 20/80 on the right. Fundu- travenous methyl prednisolone is administered over five scopic and visual field tests were normal. Swinging Marcus Gunn pupil on םdays at a dose of 1000 mg/day, followed by a 12-day flashlight test showed a 2 prednisone taper (60 mg/day for four days, 40 mg/day for the right. The rest of the neurological examination four days, 20 mg/day for four days). Adverse effects of was unremarkable. A few days later, her vision the chronic use of steroids are well known. seemed to worsen, especially after physical activity.

Prevention of Relapses Summary A 35-year-old woman with right orbital pain, diminished vision worsened by exercise, and right affer- The prevention of relapses is based on the use of ent pupillary defect on examination. interferon-beta that includes three preparations interferon beta-1b (Betaseron) and two interferon beta-1a (Avonex Localization and Rebif). Other prophylactic agents include glatiramer acetate (Copaxone) and mitoxantrone (Novantrone). In- Acute or subacute visual loss can be caused by optic neu- terferon beta-1b has demonstrated a reduction of 30 per- ritis, ischemic vascular disease, or increased intracranial cent in clinical relapses and decreased MRI disease ac- pressure. tivity. The dose in 250 mcg injected subcutaneously every Optic neuritis is characterized by acute or subacute uni- other day. Common adverse effects include flu-like symp- lateral visual loss associated with pain that increases with toms (fever, , sweating and chills), headache, de- eye movements and precedes the onset of visual symp- pression, injection site reactions, menstrual abnormali- toms. The visual impairment progresses rapidly over one ties, decreased white cell and platelet counts, and liver to two weeks and then starts improving over the next enzymes elevation. month. The presence of a relative afferent pupillary defect Avonex has shown to reduce the frequency of the at- (RADP), also termed a Marcus Gunn pupil, characterized tacks and also has demonstrated a reduction of gadolin- by an abnormal response to light stimulation is commonly ium GD enhancing lesions on MRI. The injection is given observed. Uthoff’s phenomenon, characterized by wors- once a week intramuscularly in a dose of 30 mcg. Ad- ening of vision with exercise, fatigue, stress, or increased verse effects are similar to Betaseron but skin reactions body temperature can be noticed during the recovery are not observed. Rebif is given three times a week sub- stage of optic neuritis (Matthews). In the retrobulbar form cutaneously at doses of 22 or 44 mcg. Side effects are of optic neuritis, funduscopic examination is normal or comparable to those of Avonex. will show some pallor of the disk if prior episodes of Glatiramer acetate (Copaxone) has demonstrated a de- demyelination have occurred. Visual function shows a crease in relapse rate of 29 percent. It is administered at generalized involvement of the visual field or a large cen- a dose of 20 mg daily subcutaneously. Common side ef- tral scotoma. fects include injection site reactions, such as erythema The vignette clearly describes a case of optic neuritis and swelling, and systemic postinjection reactions, such but other causes of unilateral visual loss need to be also as anxiety, palpitations, chest tightness, and shortness of considered in the differential diagnosis. breath, lasting less than one hour. Optic neuritis is an inflammatory disorder of the optic Mitoxantrone (Novantrone) has immunomodulating nerve and represents the initial manifestation of multiple effects by suppressing humoral activity and acting on T sclerosis in up to 20 percent of cases (Hogancamp and and B cells (Arnason and Wojcik). It reduces the fre- Noseworthy). quency of clinical relapses and the neurological disability It is an important feature of Devic’s disease character- in patients with secondary progressive, progressive re- ized by bilateral optic nerve and spinal cord involve- lapsing, or worsening relapsing-remitting MS (Kaba). ment, and clinically by sudden and complete visual loss The dose has been established as 12mg/m2 every 3 first in one eye and then in the other, associated with months. Adverse effects include nausea, hair loss, amen- and weakness that progress to paraparesis orrhea, and bone marrow suppression. and tetraparesis. Syringomyelia and Syringobulbia 137

Infectious and inflammatory disorders can also be re- ANA, ACE, and so on, are usually obtained. A chest x- sponsible for optic neuritis, particularly bacterial, viral, ray and CSF studies are important in selective cases to and parasitic infections. , , toxoplas- exclude CNS and systemic infections. MRI of the brain mosis, Borrelia burgdorferi, and viral encephalitides assumes a primary role in the diagnosis of multiple scle- (measles, , chickenpox, , rosis and to exclude a compressive lesion. herpes zoster, CMV, HIV, HTLV-I) can be responsible for a clinical picture of optic neuritis. Immune-mediated in- Treatment flammatory disorders include systemic lupus erythema- The optic neuritis treatment trial study group determined tosus, Sjo¨gren’s syndrome, Behc¸et’s disease, and ulcera- several guidelines for the management of acute optic neu- tive colitis. ritis. There is a consensus that in patients presenting with the typical manifestations of optic neuritis, such as sub- Differential Diagnosis acute onset of painful unilateral visual loss that improves In the differential diagnosis of acute or subacute visual within four weeks, blood tests, CXR and CSF studies are loss, several conditions need to be considered: of limited value. Oral prednisone is not recommended because according to the study it did not show any effi- • Ischemic optic neuropathy. cacy in improving visual outcome and caused an in- • Compressive and infiltrative lesions. creased rate of new episodes of optic neuritis (Kauf- • Hereditary optic atrophies. mann). MRI of the brain needs to be considered, • Toxic and metabolic disorders. particularly as a predictor of MS development. Treatment with high doses of IV methylprednisolone has been rec- Ischemic optic neuropathy, which usually affects the ommended if the MRI study is highly suggestive of a prelaminar portion of the optic nerve, is called anterior demyelinating disorder consistent with multiple sclerosis ischemic optic neuropathy and can be arteritic and non- or if a rapid recovery of vision is desired. arteritic. The nonarteritic form, which affects older pa- tients particularly with hypertension, diabetes, and arte- riosclerosis, is characterized by painless visual loss, Syringomyelia and Syringobulbia maximal at onset, altitudinal field defect, and swelling of the optic disk. The arteritic form occurs in the elderly and is characterized by headache and systemic symptoms, such as fatigue, myalgia, arthralgia, elevated sedimenta- Vignette tion rate, and previous episodes of amaurosis fugax. A 22-year-old nurse’s aide was in excellent health Infiltrative and compressive lesions involving the optic until six months ago when she fell on a wet floor nerve or the orbit, pituitary gland, and parasellar struc- in a supermarket, striking her head. Two days later tures, such as tumors (gliomas, meningiomas), infections, she started complaining of vertigo, right hand inflammatory processes, and thyroid ophthalmopathy, numbness, and severe headache. She felt unsteady can be responsible the occurrence of progressive visual and had the impression that objects in her vision loss, usually in combination with other signs and symp- were jumping back and forth. After a prolonged toms, such as proptosis, ophthalmoparesis, and so on. coughing bout, she developed more vertigo, diplo- Hereditary optic neuropathies include Leber’s optic pia, and slurred speech. On neurological exami- neuropathy, which affects young individuals, particularly nation the aide was alert and cooperative. The right males, in the second and third decades of life and is char- pupil was 2 mm and the left was 4 mm briskly re- acterized by maternal transmission and sudden, progres- active. A slight right ptosis was identified. She had sive, painless loss of central vision affecting first one eye marked rotatory nystagmus when looking down and and weeks to months later the other. the tongue deviated to the left. DTR were brisk in Optic neuropathies associated with nutritional defi- the lower extremities and could not be elicited in ciencies and toxic agents, such as B1 and B12 deficiency, the upper extremities where fasciculations were tobacco, alcohol, isoniazide, and ethambutol, usually noted. Pinprick sensation and temperature were de- manifest with a subacute, bilateral, central visual loss. creased on both arms. Gait was mildly spastic. She had a stiff neck and the hairline was low. Diagnosis Summary A 22-year-old woman with the following neu- Neurological and ophthalmological consultations, includ- rological symptoms that started after a fall: ing visual field evaluation, are the first steps in the di- agnostic workup. Blood tests, including cell count and • Vertigo. differential, ESR chemistry panel, VDRL, Lyme titer, • Right hand numbness. 138 13. Multiple Sclerosis

• Headache. • Unsteady gait. • Hyperreflexia and spasticity of the lower extremities • Jumpy vision. are due to corticospinal tract involvement.

After a bout of severe coughing (that implies the Val- Once the lesion is localized (in this case, the intrinsic salva’s maneuver) the symptoms worsened, with brainstem and cervical cord area) then diagnosis and dif- • Increased vertigo. ferential diagnosis need to be considered. • Diplopia. • Dysarthria. Differential Diagnosis The neurological examination shows In the differential diagnosis, important consideration needs to be given to syringomyelia and syringobulbia that • Pupillary anisocoria with right ptosis. can be associated with malformations and developmental • Tongue deviated to the left. anomalies or can be secondary to other pathology such • Rotatory downbeat nystagmus. as tumors and trauma. • Areflexia of the upper extremities and fasciculations. Intramedullary tumors present some diagnostic diffi- • Hyperreflexia of both lower extremities. culty in the differentiation from a syringomyelic process • Hypoesthesia to pain and temperature on both upper because they can be associated with central cord cavita- extremities. tion. According to Foster, the highest percentage of cav- itation occurring with tumors is in cases of von Hippel- Localization Lindau disease or von Recklinghausen’s disease. Localization of the lesions causing the abnormalities de- Extramedullary usually manifest with ra- scribed in the vignette include the brainstem and the dicular pain, signs of , and in- cervical cord. The patient in the vignette has signs and volvement of the dorsal column without sensory disso- symptoms significant for an intrinsic brainstem lesion, ciation. The combination of upper and lower motor predominant on the left. neuron signs and dissociated sensory loss are more sug- The description of jumpy objects in front of the pa- gestive of an intramedullary cord lesion. tient’s vision describes oscillopsia. Oscillopsia is defined Foramen magnum tumors need special consideration as the false illusion of back and forth movements of the because of the difficulties in the differentiation from sy- environment created by the repeated transit of images of ringomyelia and syringobulbia. stationary objects across the retina (Glaser). The onset of Neurofibromas (schwannomas or neurilemmomas) and oscillopsia and vertigo suggests a brainstem problem meningiomas are the most common types of tumors in (Barnett et al.). this location (Adams and Victor). Rotatory nystagmus may indicate a localization to the Foramen magnum tumors can have a variety of symp- medullary area. Downbeat nystagmus in the primary po- toms that include neck and suboccipital pain and stiffness, sition is characteristic of lesions in the medullary cervical progressive spastic weakness, hand atrophy, sensory area, such as syringobulbia, Chiari’s malformation, bas- changes, and, rarely, findings indicative of posterior col- ilar invagination, and so on (Adams and Victor). umn dysfunction or a syringomyelia-type of sensory dis- The involvement of the hypoglossal nerve in the me- sociation. Lower cranial nerve palsies can occur as well dulla is suggested by the ipsilateral tongue deviation to as downbeat nystagmus, Horner’s syndrome, and cere- the left. bellar ataxia. The signs suggesting a cervical localization can be Syringomyelia complicating spinal trauma usually summarized as follows: manifests months or even longer after the initial and is a rare event. • Right Horner’s syndrome is indicated by pupillary an- Among the congenital anomalies, Chiari’s malforma- isocoria (right 2 mm, left 4 mm) and right ptosis. This tion, characterized by caudal localization of the cerebellar is caused by involvement of the ciliospinal center of tonsils below the foramen magnum, and other malfor- Budge with C8–T2 lesions. mations can be associated with syringomyelia and sy- • Areflexia and fasciculations of the upper extremities ringobulbia, therefore creating diagnostic difficulties in indicate segmental involvement of the anterior horn separating the effects of the two disorders. cells at the level of the lesion. Chiari’s malformation can present with signs of brain- • Segmental dissociated anesthesia to pain and tempera- stem and cerebellar compression such as downbeat nys- ture at the level of upper extremities is caused by in- tagmus, tongue atrophy, hoarse voice, dysarthria, ataxia, volvement of the decussating fibers of the spinotha- and symptoms and signs of hydrosyringomyelia. lamic tract. Other malformations, such as basilar invagination of 139 the skull or basilar impression (platybasia), may simulate vignette, several categories of disorders, such as demye- the symptoms of syringomyelia and may coexist with this linating, infectious, inflammatory, vascular, neoplastic, process. nutritional, hereditary, and degenerative need to be ALS is easily ruled out by the sensory loss described mentioned. in the vignette. Subacute spinal cord dysfunction is often a manifes- Multiple sclerosis may mimic syringomyelia, but hy- tation of multiple sclerosis but other causes, such as struc- poreflexia and fasciculations are unlikely in MS. tural and compressive disorders, need to be excluded, The mention in the vignette of low hairline may sug- such as tumor, malformations, or herniated disks causing gest a developmental lesion at the craniovertebral cord compression. A careful history is necessary, particu- junction. larly when other clinical signs and symptoms of multiple sclerosis are not apparent. Treatment Several infectious disorders are responsible for causing , such as bacterial, viral, fungal and parasitic The treatment is based on the appropriate cause. diseases. Spinal syphilis, tuberculous myelitis, Lyme dis- ease, schistosomiasis, cryptococcosis, herpes infections, AIDS, and HTLV-I are just some of the many responsible Transverse Myelitis agents. Noninfectious inflammatory disorders, such as sys- temic lupus erythematosus, also need to be considered in Vignette the differential diagnosis because SLE is a well-known cause of transverse myelitis. Spinal cord symptoms may A 42-year-old lawyer started complaining of numb- be steadily progressive, recurrent or, more commonly, ness and tingling involving the bottom of her left rapid or sudden, with little tendency to remission (Mat- foot one week ago. The tingling then traveled to her thews). In 40 percent of the patients, myelopathy pre- left leg and lower trunk. Two days later, she woke cedes the diagnosis of SLE, but most cases have evidence up feeling numbness in her right foot and had some of multiple organ system dysfunction at the time of pre- difficulty judging bladder fullness. She had fallen sentation (Aminoff). twice after catching her toes on a curbstone and Other collagen vascular disorders, which can be easily was complaining of mild chest pain. Her past medi- ruled out, are Sjo¨gren’s syndrome, mixed connective tis- cal history was unremarkable. She was recently on sue disease, and so on. a week’s vacation to Mexico where she experienced Vascular diseases of the spinal cord (ischemic or hem- some mild diarrhea. On examination, her mental orrhagic) can present with spastic weakness and can be status and cranial nerves were normal. Abdominal caused by thrombotic occlusion, trauma, vascular mal- reflexes were absent. Knee and ankle jerks were formations, or coagulopathies. Ischemic disease of the brisk and the left toe upgoing. There was decreased spinal cord most commonly involves the territory of the vibration of both great toes. Gait was spastic. anterior spinal artery and causes acute onset of weakness (instantaneously or over an hour or two and commonly Summary A 42-year-old woman with progressive more rapidly than the other ) (Adams and numbness, unsteady gait, bladder dysfunction, chest pain, Victor). Spastic weakness, dissociate sensory loss with signs of bilateral upper lesion with lower involvement of pain and temperature, and sparing of vi- extremities hyperreflexia and left Babinski; hypoesthesia bration and position sense below the level of the lesion, to vibration on both toes. and sphincteric abnormalities are characteristic. Vascular malformations of the spinal cord are another Localization important consideration in the differential diagnosis. The vignette clearly localizes to the spinal cord. Involve- Compressive myelopathies due to or tumor ment of the spinal cord is manifested with spastic weak- (extramedullary or intramedullary) are also included in the ness, paresthesias, numbness, and bladder dysfunction. differential diagnosis. Nutritional deficiencies, particularly Chest pain can occasionally be neurological in origin and vitamin B12 deficiency, can present as a myelopathy. can suggest disease of the corresponding level of the spi- The hereditary forms that need attention are hereditary nal cord, nerve root, or, rarely, peripheral nerve. spastic paraplegia (easily excluded in this vignette be- cause of the lack of suggestive family history) and the leukodystrophies (also excluded by the lack of other as- Differential Diagnosis sociated symptoms, such as a positive family history, a Among the diagnostic possibilities leading to progressive demyelinating neuropathy, prominent behavioral change subacute myelopathy, which is the case described in the or or marked autonomic dysfunction). 140 13. Multiple Sclerosis

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